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Probiotics for oral health: start young

By Dr. Mary Ellen Sanders

Prof. Wim Teughels from the Department of Oral Health Sciences, Leuven University, spoke at the 2018 ISAPP meeting on the topic of probiotics and prebiotics for oral health. He embraced the opportunity to speak to this audience in part hoping he could convince researchers to consider incorporating oral health endpoints in their future clinical trials.

He did a spot-on lecture, which precisely summarized available evidence for probiotics and prevention of dental caries, management of periodontal disease and reduction of Streptococcus mutans in the oral cavity. This area of research is gaining traction (see here).

One study he discussed is particularly interesting by Stensson et al. 2014 tracked caries in children at 9 years of age. This single-blinded, placebo-controlled study administered L. reuteri ATCC 55730 to mothers during the last month before their baby’s birth and to the children through age one. The number of children receiving the L. reuteri probiotic without caries was significant higher (82%) than in the placebo group (58%).  Although there are studies available that show a larger impact, the interesting aspect of this study is that it tests a very early intervention in life that seems to have an effect up to 9 years later. It is an important paper because it opens up the notion of early interventions in life, during microbial ecology development. The main message here is you don’t need to wait until there are teeth to start working on dental health later in life. In fact, interventions for dental health can start during pregnancy and by this:

We do not know what would have happened if the probiotics were given during the whole 9 years of life. Dentists who are interested in prevention should be interested in such data.

Several meta-analyses have summarized data for dental caries and management of periodontal disease. These reviews are useful in that they summarize the totality of evidence. But combining data on different strains might not be justified, as different strains may utilize different mechanisms to achieve effects, and therefore should not be considered as the same intervention. See here, here, here and here.

In sum, there appears to be a growing body of evidence that probiotic administration may impact several indicators of oral health: dental caries, gingivitis and periodontitis. More research is needed to understand the impact of probiotic supplementation on the oral microbiota and if clinical benefits are mediated by microbiota changes. It’s also important to understand which strains will deliver the strongest benefits, although L. reuteri has several, positive studies, and the importance of dose and temporal factors with dosing.

live-dead-probiotics

Dead bacteria – despite potential for benefit – are NOT probiotics

This blog is a re-posting of a blog initially published on www.usprobiotics.org on July 5. By Dr. Mary Ellen Sanders

At the 2018 International Scientific Association of Probiotics and Prebiotics (ISAPP) meeting in Singapore, two renowned speakers reported unpublished research documenting the health benefits of dead bacteria.

Prof. Hill showed that an inactivated Lactobacillus strain reduced anxious behavior, reduced cortisol levels, and impacted the microbiome in a mouse model. Prof. Patrice Cani showed that heat-killed Akkermansia muciniphila were sufficient to ameliorate obesity and diabetes in mice. Both professors made the point that these microbial preparations were not probiotics.

Prof. Colin Hill is the lead author on the oft-cited and -downloaded (over 40,000 times) ISAPP consensus paper reaffirming the definition of probiotics, which emphasizes that probiotics must be alive when administered. This, of course, does not preclude health effects of dead bacteria. One just must remember that dead bacteria are NOT probiotics. Many different types of microbe-derived substances such as metabolites, cell wall fragments, enzymes, and neurochemicals, can have beneficial physiological effects. A 2016 review by de Almada et al. lists a couple dozen published studies of physiologically active dead bacteria.

Preserving the long-accepted definition of probiotics as ‘live microbes’ is important to the many stakeholders involved in the field. Consumers should be able to purchase a product labeled as ‘probiotic’ and know that it contains an effective level of live microbes. Regulators should know that a product without an adequate level of live microbes is fraudulent if called a probiotic. Scientists should be able to use the term and have reviewers and readers understand that they are referring to functions of live microbes. An agreed-upon definition enables us to be precise when discussing an issue. Saying that because dead bacteria have a health effect and they should be called ‘probiotics’ is like saying that because vitamin D has a health benefit, the term ‘vitamin A’ should include vitamin D.

What are implications of the fact that dead microbes may have health effects?

Stewards of the probiotic field can expect increased frustration with popular press writers. I’ll use a recent example to make this point. The June 2018 Cooking Light Magazine /Special Gut Health Issue included an article that lists sourdough bread as a top probiotic-containing fermented food. When the error about misusing the term ‘probiotic’ to describe a food that contained no live probiotic bacteria was pointed out to the editor by Jo Ann Hattner, MPH RD author of Gut Insight, Cooking Light chose to ignore advice from an expert and justify their mistake by using an irrelevant observation that both live and dead cells in probiotic products may generate beneficial biological responses. Apparently, the expertise she derived from a paper that described the “probiotic paradox” trumped the considered opinions of global expert scientists/researchers and the FAO/WHO, who agree that probiotics must be alive when administered. It’s quite a simple concept. It is true that some dead microbes may have some health benefit (although evidence of such an effect is much lower than that available from controlled human trials on actual probiotics), but they are NOT probiotics.

Confusion. Some audiences will be confused by the idea that probiotics that are killed can have health benefits. Inaccurate writers, such as the Cooking Light author above, will perpetuate this error. This is unfortunate, since the probiotic concept is a long-standing one, backed by much mechanistic and clinical evidence. Conflating probiotics with dead bacteria will lead to confusion over important aspects of an effective probiotic product.

Overages.  It is not uncommon for commercial products to be formulated with live microbes at time of manufacture that far exceed the number claimed on the label. This is to assure that the product meets label claim at the end of shelf life, as probiotics often die to some extent during storage. Sometimes this ‘overage’ can reach 10-fold more than the level guaranteed on the product, although more typically it’s 2- to 5-fold. If over the course of shelf life the viable count drops to label claim, then dead microbes may comprise as much as 90% of the microbes present. We don’t know if these dead bacteria – although no longer probiotics – have physiological benefits, as no studies have been conducted on this form of inactivated cells, but it’s an interesting possibility. When we study a probiotic product, perhaps that product needs to be characterized by both the level of live and dead microbes that are present. Means of inactivation, such as heat, pressure, irradiation, or sonication, may impact the physiological activity of the resulting dead cells.

Opportunity.  Keeping probiotics alive in commercial products is a challenge. Research such as Prof. Cani’s targets an expanded range of microbes – many isolated from the human GI tract – that cannot be easily grown and stabilized in commercial products. Further, these microbes lack the history of safe use that food-associated microbes have, and so administration of high numbers of these next-generation probiotics will require proof of safety. If these microbes can be killed and still deliver health benefits, the commercialization process could be simplified.

ISAPP may need to consider convening another consensus panel to address these newly emerging terms, such as postbiotic and paraprobiotic. Then we can all be on the same page when using these terms, which have important scientific, nutritional and clinical impact. Of course, even if ISAPP does this, authors may still choose to ignore it.

efficacyvseffectiveness

Efficacy and Effectiveness Studies

By Michael D. Cabana, MD, MPH

In the world of clinical trials, reproducibility (or consistency) of results across different clinical trials improves clinicians’ confidence in an intervention (Hill, 1965).  However, when reviewing the evidence for a probiotic or prebiotic supplement, the results are sometimes conflicting.  One study claims an intervention may work.  Another study claims that an intervention may not work. So how does the clinician deal with this situation?

To know how much confidence to place in any claim of benefit, clinicians need to consider the totality of the evidence and the quality of the studies. One tool is the systematic review process, which in an unbiased manner searches for all studies for a particular intervention, and when possible, combines results into a meta-analysis. The ‘summary’ of these data point to either an effect or no effect. The best way to combine data is using an individual patient-data meta-analysis (IPDMA). In addition, a clinician should determine whether the clinical trial is an effectiveness study or an efficacy study (Singal 2014).

 

Efficacy or Effectiveness?   

Efficacy studies ask, “does the intervention work in a defined (usually an “ideal”) setting?”  In general, the inclusion criteria for study participants will be very selective.  Patient adherence tends to be closely monitored. The clinicians conducting the trial may be specially trained in the intervention and its application. The intervention occurs in an ideal setting and the risk of other confounding interventions (e.g., unusual diets, concurrent treatments) will be limited.

On the other hand, effectiveness studies ask, “Does the intervention work in a real-world setting?”  The inclusion criteria for study participants tends to be less selective.  Patient adherence to the protocol is not necessarily strictly enforced. The clinicians conducting the trial tend to be representative of the typical physicians who would treat this condition.  The intervention occurs in a more ‘real-world’ setting where the presence of other confounding factors may be present.

For example, two relatively recent studies both examined the effect of a probiotic intervention, L. reuteri DSM 17938 for the treatment infant colic.  A study conducted by a team in Italy (Savino et al. 2010) noted that the intervention reduced colic symptoms; however, the study conducted by a team in Australia (Sung et al. 2014) showed no effect on colic.

Why the different results? In the Italian study, all the infants were breastfed.  In addition, the breastfeeding mothers limited their dairy intake.  The infants tended to be younger (mean age 4.4 weeks) and tended not to have other treatments for colic or gastrointestinal symptoms.  In contrast, the infants in the Australian study were breastfed or formula fed. The infants were older (median age 7.4 weeks) and were more likely to have been exposed to other treatment for gastrointestinal symptoms (such as histamine-2 blocker or proton pump inhibitors).  The infants were recruited from many different settings such as the emergency department.

Although both the Italian and the Australian study evaluated the same probiotic intervention for the same condition, the studies offer different information in terms of efficacy and effectiveness.  Describing a study as either an “efficacy” study or an “effectiveness” study is not always dichotomous.  Rather, these studies exist on a spectrum, from being more like an efficacy study versus more like an effectiveness study. In the example above, the Italian study had stricter criteria and fewer confounding factors.  As a result, it would tend to be classified as an efficacy study.  The Australian study enrolled infants with colic who were older and had a greater likelihood to be exposed to other interventions.  This study would tend to be classified as more of an effectiveness study.  The fact that the Australian study was a null study does not mean that the intervention was not effective in the ‘real world’.  Rather, for the patients enrolled, the treatment was not effective when used in that particular setting and context.  Perhaps you may encounter infants with colic who have feeding history and medical history more like the infants from the Italian study. Understanding the context of the studies helps identify those characteristics that may or may not apply to the infants with colic who you may treat in your clinic.

 

Which is better: Efficacy or Effectiveness?

When developing a new or experimental intervention, an efficacy study might be important to increase the likelihood of detecting a positive change.  However, “real world” factors may make a difference in how a product is used.  Perhaps an intervention might be inconvenient (due to multiple doses throughout the day) or unpalatable for the patient.  Perhaps the dosing regimen is complicated and the primary care providers don’t apply the correct dosing for patients. In these cases, an effectiveness study might be a better guide to how useful the intervention will be in clinical practice.

As a final note, it can be tempting to simply read the abstract of a clinical trial to assess the results of a study.  However, in many instances the crucial details of the study (e.g., how the study participants were selected, who was included or excluded, what type of clinical setting was used) are buried in the methods section of the study.  Patient diet, exposure to other treatments and comorbid conditions are all common confounding factors encountered in trials evaluating supplements.  When reading through the literature and understanding if a study is applicable to your practice, be sure to understand the full context and purpose of the study.  “Was this study useful for determining clinical efficacy or clinical effectiveness?” is an important question for readers of probiotic and prebiotic clinical trials. Keeping this question in mind may help you better resolve what may appear to be inconsistency among clinical trials.

clinician_guides

Guides for use of probiotics in the clinic – some recent ISAPP initiatives

By Mary Ellen Sanders, PhD

At the ISAPP meeting earlier this month, Prof. Dan Merenstein, MD, presented a summary of recent ISAPP initiatives focused on helping translate the evidence of probiotics and prebiotics into clinical action.

A 2013 paper reported that 87% of hospital formularies surveyed in the United States carried at least one probiotic. Yet when Merenstein looked at the names of the products tested, many were not supported by evidence for such uses. This highlights the need for clinicians to have access to clear, evidence-based probiotic use guidelines.

ISAPP has worked through a variety of avenues to get information into the hands of clinicians. It has supported continuing education credit activities, webinars, collaboration with clinical organizations to develop guidelines, publications in clinical journals, presentations at clinical meetings, and simplified summaries using infographics and videos. Some examples include the following.

 

World Gastroenterology Organisation Global Guidelines – Probiotics and Prebiotics

This document is the most visited and downloaded of all WGO guidelines. In 2017, under the leadership of Prof. Francisco Guarner, MD PhD, this document was updated. Three current ISAPP board members were part of the process and ISAPP provided funding. See here.

 

Petitions

ISAPP petitioned the United States Preventive Services Task Force to examine the role of probiotics in preventing antibiotic-associated diarrhea. They considered the petition, but didn’t feel it fit their mission.

ISAPP petitioned American Academy of Family Physicians to consider reviewing the evidence for probiotics for AAD to include in their evidence-based guidelines. This is under consideration.

After attending 2017 ISAPP, Dr. Claire Merrifield BSc MBBS PhD led an effort to have NICE Clinical Knowledge Summaries mention probiotics for AAD in an effort to get local groups to adopt guidelines. This has met with limited success. See here.

 

CME or CE activities

On April 17, 2018, Merenstein and Mary Ellen Sanders PhD served as faculty for a CME-eligible webinar sponsored by Medscape on “Navigating the World of Probiotics. Helping Patients Make Good Choices”. The activity is available on Medscape’s website here.

In February 2018, Merenstein published a CE activity with the Pharmacy Times titled “The Expanding Health Benefits of Prebiotics and Probiotics”. See here

Upcoming in October 2018, Merenstein will present “Probiotics and the GI Tract. What Should a Busy Clinician Know” at the American Academy of Family Physicians Annual Conference. This conference is attended by over 4,000 physicians and is focused on clinical practice. The event, eligible for CME, will be recorded and made available after the live presentation.

ISAPP co-founder, Prof. Glenn Gibson has or will present 6 lectures over 2017 and 2018 on the topic of “The Learning Curve for Probiotics and Prebiotics.” These lectures are available for CME credit and are targeted to family doctors, gastroenterologists, pediatricians, and dieticians in the UK.

Numerous CME presentations over 2017-2018 have been given by ISAPP board members:

M.D. Cabana:

  • “Probiotics: Friend or Folly?”  American Academy of Pediatrics National Conference and Exhibition. Chicago, IL. September 17, 2017.  The audience was about 450-500 clinicians.
  • “Probiotics in Primary Care Pediatrics: Diarrhea, Colic & Eczema.” American Academy of Pediatrics California Chapter 1 Meeting. 300 clinicians
  • “Probiotics for Colic?” Zuckerberg San Francisco General Hospital. Department of Pediatrics Grand Rounds. San Francisco, CA.
  • “Probiotic Interventions for Colic” UCSF Benioff Children’s Hospital, Oakland.
  1. Reid:
  • “Effects and importance of microbiota on urogenital health in women.” 16th Annual Congress of Gynecology and Obstetrics, Antalya, Turkey. 300 obstetricians and gynecologists.
  • “Probiotics to whom for what?” Health World Ltd International Congress Natural Medicine 2017, Hunter Valley, New South Wales, Australia,.601 healthcare practitioners and naturopaths.
  • “The microbiome and how it relates to maternal/newborn care.” The Graham Chance Lectureship, Perinatal Research Day, London, ON. 100 neonatologists and pediatric experts.
  • “Microbes and the brain.” Integrative Healthcare Symposium, New York City. 500 naturopaths and various specialists.
  • “Probiotics and detoxification.” Environmental Health Symposium, Scottsdale, Arizona, 8th April. 500 naturopaths and various specialists.

 

Webinars

On June 28, ISAPP co-founder, Prof. Glenn Gibson, will present a webinar along with Profs. Ted Dinan and Ian Rowland titled “Why is everybody talking about gut microbiota?” Sponsored by the British Nutrition Foundation, this webinar will target healthcare professionals in the UK and Europe. See here.

 

Publications in clinical journals

Several ISAPP board members

  • Evidence-Based Probiotic Use in Family Medicine. Submitted, Journal of Family Practice. Merenstein/Sanders/Tancredi
  • Probiotics for Human Use. In press, Nutrition Bulletin. Sanders/Merenstein/Hutkins/Merrifield
  • Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Invited review in preparation, Nature Reviews Gastroenterology and Hepatology. Gibson/Reid/Sanders/Merenstein
  • Clinical perspectives of prebiotics and synbiotics. In preparation, Gastroenterology. Gibson/Quigley

 

Featured on ISAPPscience.org

Infographics

 

Videos

  • What is a probiotic?
  • Health benefits of probiotics
  • Are all probiotics the same?
  • How to choose a probiotic

 

General guidelines for choosing probiotics and prebiotics

Some initiatives that Merenstein championed were a direct result of ideas generated during the discussion group he led during the 2017 ISAPP meeting in Chicago.

 

Image courtesy of nursingschoolsnearme.com/

East meets West at ISAPP’s first meeting in Asia

By Mary Ellen Sanders, PhD

The International Scientific Association for Probiotics and Prebiotics (ISAPP) recently convened its first meeting held in Asia, with the modern hub of Singapore as a host city. The meeting featured a two-day open registration meeting, attended by nearly 250 scientists, health professionals, and industry representatives, and a third day of smaller discussion groups by invitation. The meeting provided a rare opportunity for non-members to attend. It provided a dynamic forum for sharing different clinical experiences and regulatory nuances amongst the continents, as well as allowing attendees to better appreciate the research being performed in the Asian region.

Here are a few speaker highlights:

 

Mimi Tang MD

Tang presented the results of a double-blind, randomized controlled trial examining the effect of probiotic supplementation combined with oral immunotherapy (OIT) to decrease the risk of peanut allergy in children. Peanut allergy is one of the fastest growing food allergies in children. In the Probiotic and Peanut Oral ImmunoTherapy [PPOIT] study, children randomized to the intervention group had increased rates of sustained responsiveness to peanut several weeks after discontinuation of the treatment. Tang discussed the implications of the study, as well as current, larger clinical trials that are building upon these findings.

 

Dr. Bruno Pot

The Lactobacillus genus is taxonomically abnormally heterogeneous. Currently, the 231 Lactobacillus species range from a genome size of 1.23 – 4.91 megabases, have a GC content of 32-57% and an average nucleotide identity that is typical for a family or worse. Such ranges are far beyond what is acceptable for a bacterial genus. Experts are recommending that the current genus should be split into 12 new genera. Some well-known lactobacilli would be re-named, which may have important repercussions commercially and legally.

 

Profs. Colin Hill and Patrice Cani

Hill described how lactase in yogurt cultures improves lactose digestion; he emphasized how mechanisms that drive probiotic activity are complex. Some scientists are searching for a single molecule that drives probiotic health benefits—but it is unlikely to be found.

Hill noted even inactivated (non-living) microbes may have health effects—for example, a study showed that a dead Lactobacillus strain reduced anxious behavior, reduced cortisol levels, and impacted the microbiome in a mouse model. Work by Prof. Patrice Cani showed that heat-killed Akkermansia muciniphila were sufficient to ameliorate obesity and diabetes in mice. Does this suggest that we will need to start quantifying probiotics based on biomass as well as CFU?

 

Profs. Hani El-Nezami, Gregor Reid and Akihito Endo

These three speakers illustrated the important impact of environmental toxins (extremely potent aflatoxins, pesticides, and heavy metals) on humans and wildlife. They showed how certain probiotic strains can decrease aflatoxin absorption and even degrade them; sequester heavy metals and pesticides to reduce their uptake; and enhance resistance to honey bee colony collapse disorder that threatens the world’s food supply.

 

Prof. Wim Teughels

To date, 11 studies have been published on probiotics with a low ‘number needed to treat’ for prevention of dental caries in infants, toddlers, and adults. One study showed the benefits of administered L. reuteri, following children for nine years after they were treated as infants before any teeth had emerged. Also, data exist for probiotics influencing other oral health endpoints, including periodontal infections, oral candida infections, and halitosis.

 

The discussion groups on day three of the conference addressed a range of topics:

  • Possibilities to harmonize global probiotic and prebiotic regulations—Chaired by Seppo Salminen (Finland), Yuan Kun Lee (Singapore), and Gabriel Vinderola (Argentina)
  • Fermented foods for health: East meets West—Chaired by Bob Hutkins (USA), Paul Cotter (Ireland), and Liu Shao Quan (Singapore)
  • Potential value of probiotics and prebiotics to treat or prevent serious medical issues in developing countries—Chaired by Daniel Merenstein (USA), Reuben Wong (Singapore), and Colin Hill (Ireland)
  • Prebiotics as ingredients: How foods, fibres and delivery methods influence functionality—Chaired by Glenn Gibson (England) and Karen Scott (Scotland)

 

These workshops often produce peer-reviewed publications based on the discussion outcomes, so stay tuned for these developments. (See here for a list of ISAPP publications.)

The full meeting report is being developed and will be posted on the ISAPP website shortly.

The 2019 meeting will return to ISAPP’s normal format, hosted by Dr. Sarah Lebeer in Antwerp, Belgium.

 

bowling_1

ISAPP is coming to Asia – the hidden reason

By Prof. Glenn Gibson

In just a few days ISAPP will host its first meeting outside of Europe or North America, when we have an open conference in Singapore1,2. There are about 200 registrants and we cannot wait. The meetings are always scientifically informative but fun also. These are main drivers behind our annual jamboree, but this year there is another task…… I am hoping that first timers to ISAPP, and particularly our Asian friends, break with tradition and pronounce the name of the organisation correctly.

I have written one blog in the 56 years of my existence. This first was last year on the various social events we have at the meetings. But this was prior to Chicago in 2017, where we had a bowling alley experience. My PhD student Xueden Wang (Holly) has never let us forget her winning efforts at this:

bowling_1

The above picture and Holly’s endless bragging came to an abrupt end however, when we had our lab Christmas party in December3 – also at a bowling alley this time in Wokingham UK:

Let’s call that revenge of the supervisor shall we? The open top bus parade is now cancelled Holly I am afraid. By the way, if you don’t know what Chicago or Wokingham look like, then both are pictured below. I will leave you to guess which is which:

uk

Anyway, I disgress (justifiably). This is therefore my second blog, and there is a reason for dusting off the quill pen and rehearsing the hieroglyphics once more.

In the last few years ISAPP has published 2 consensus papers, one on probiotics and one on prebiotics4. What we cannot agree on, however, is how to say the name of our esteemed society. Some say ISAPP with the I as “eye”, while others say ISAPP (with the I as in sIt). Admittedly, there is a slight bias in numbers as it is possible to count on the fingers of one finger the number of people who use the latter. It is me. So, that makes about 852 attendees at previous ISAPP meetings incorrect.

Think of the full name of the ISAPP organisation and say it to yourself now…………………

Did anyone say Eye-Nternational? Or did you say International?

At this stage, I should just say that the case for the prosecution is concluded and no further witnesses your honour!

However, let’s look at things a little more closely. If the anarchists, heretics and Eye-Sappers get their way then we may need to change the logo of the organisation to:

eye ISAPP_logo

We see the letter “I” in front of many things these days such as i pad, i mac , i max, i alex cross, i pod, i robot. A quick search of the internet (or as some say eyeNternet) suggests that the “I” can stand for individual, imagination or internet, but usually refers to intelligent. We might have to live with ISAPP standing for intelligent sapps. Here is a picture of 2 saps:

 

Still, 852 people can’t be wrong. I’ll put that another way – 852 people are wrong. So the spotlight turns to Singapore to show us the light, the truth and the way forward.

But……. It gets worse. The terms probiotic and prebiotic are not used on products in Europe now as they are an implied health benefit. Let’s put aside that the very body who devised this “rule” have turned down all but about one health claim. If we go along with this puffed up lunacy5 then we might have to call ISAPP:

International Scientific Association for @%?!&.. and @%?!&..

Maybe we can get away with just using the first letters of these disgustingly offensive, abhorrent and abusive terms. So, ISAPP becomes:

International Scientific Association for P@%?!&.. and P@%?!&..

It still does not seem right, so ISAPP becomes:

International Scientific Association for PAP

Now we are getting somewhere, as PAP means Noun. 1. Nonsense, rubbish. 2. Faeces. Verb. To defaecate. e.g. ‘He was so scared he papped his pants.’.” This embodies exactly what ISAPP is all about and where pro/prebiotics work!!! So, I propose another new logo:

ISAPP_logo 

1I’ll be flying there with British Airways. One highlight is always the safety demo where they say “in the unlikely event that the plane should land on water.” I always feel that “unlikely” is not quite definitive enough. If you were to ask at check in about the chances of the 777 landing on water and the reply was “er… well…on balance it is unlikely”, you would probably not board the old crate.

2Travel tip: Always aim for row 13 and upon reaching it say “oh no, me and my luck, I’m in death row again”, it often leads to vacating of the seat next to you.

3Also attended by a group of leading food science researchers, who face such crucial issues as:

  • What is there in a chicken that makes an eggshell?
  • Why do we not eat turkey eggs?
  • Why is marmalade not just called orange jam?
  • How is some cheese orange when it made from milk?
  • Why are small chocolate bars called “fun size” when they are about half of what they should be?

4By the way, in the olden days (1995) I wanted to call prebiotics parabiotics. Only because MASH was on TV at the time and featured paramedics. So these could be known as biotics that help medics.

5Please note that these opinions are those of the author and do not represent the views of EYESAPP, aside from Gregor.

vinderola in vitro blog

The need to improve in vitro testing of future probiotics

By Prof. Gabriel Vinderola, Instituto de Lactología Industrial (INLAIN, UNL-CONICET), National University of Litoral, Argentina and Prof. Seppo Salminen, Functional Foods Forum, Faculty of Medicine, University of Turku, Finland

In a recent review we compared the in vitro tests for probiotics to the in vivo studies to observe if correlations exist.

Lactobacilli and bifidobacteria have been traditionally accepted as probiotics with the basis of their long history of safe use and reported benefits. However, new species, some of them never previously consumed, are being proposed as probiotic candidates. Some basic tests have been suggested for probiotic candidates, but there is a lack of standardized in vitro protocols for the selection of new strains of probiotics. Additionally, safety assessment of new species may have to cover aspects never hitherto considered.

Vinderola and coworkers reviewed the common in vitro selection tests such as exposure to low pH and bile salts, adherence to intestinal mucus or cell lines and prokaryotic-eukaryotic co-cultures that have been traditionally used to predict the functional properties of probiotics.  At the end, the correlation of in vitro results with in vivo performance remained ambiguous. This poses challenges to research as newly proposed probiotics include often novel species never hitherto administered to humans.

The question of safety has been handled by the European QPS system and the US GRAS notifications but questions on efficacy, particularly concerning health claims, would benefit from predictive in vitro tests. These appear to predict more technological properties than safety and efficacy or health benefits.

New standardized systems need to be developed along with detailed sequencing information to be able to predict novel probiotic properties before they are tested in expensive human intervention studies. If the predictive capacity of in vitro tests fails, many potential probiotics will be left on the way from the laboratory to the application in humans and animals.

The lack of standardized protocols for in vitro and in vivo studies hampers comparison of the potential of new species and strains. There is thus a need to conduct selection of potential probiotics in a more robust manner and to focus on well-defined in vitro and in vivo (animal) studies able to predict health benefits that must still be confirmed in human interventions studies with the smallest possible error margin.

For additional perspective on this issue, see blog by Dr. Mary Ellen Sanders: Probiotic Screening: Are in vitro Tests Informative?

 

 

Reference: Vinderola G, Gueimonde M, Gomez-Gallego C, Delfredico L, Salminen S. Correlation between in vitro and in vivo assays in selection of probiotics from traditional species of bacteria. Trends in Food Sci Tech 2017: 68:83-90.

science hard blog

Those who can’t do science, do science communication?

By Dr. Colin Hill

See what I did there?  I used a title which I hope will attract the attention (or wrath) of science communicators but then put a question mark which allows me to disagree with the hypothesis posed – a good science communication bit of ‘click-baiting’.

But now that I have hopefully got your attention, let me expand on my views of how science is communicated.  By way of disclosure, I am involved in a research centre, APC Microbiome Ireland, which has a mandate from Science Foundation Ireland for each scientist to actively participate in public engagement.  This is something I initially resented, on the premise that anything mandatory should be resisted, but I have begun to appreciate that it is an important obligation for active scientists to support science communication – hence this blog and sporadic attempts to tweet and engage with the outside world.  We are very lucky to have dedicated and talented science communicators in the APC, with an extraordinarily wide brief of engaging with schoolkids, students, clinicians, industry and the general public.  To argue against my provocative title, let me make it clear our APC communicators are highly qualified and talented scientists who could easily have ‘made it’ in scientific research in academia or industry, but chose to develop their skills in science communication.

My main issue is the widespread attempts to portray science as ‘fun’ to young people.  Most science communicators dealing with adults do a great job, albeit unfortunately the message is sometimes coloured by the need to make the story interesting by linking it to a headline proclaiming a ‘new cure for cancer’ or a ‘breakthrough on superbugs’.  But it is mainly the manner of communicating to younger people that worries me.  Scientists are largely perceived as nerds by the general public, and certainly by print and online media, even more so again by film and TV, but perhaps the most by scientists themselves.  Is this why we feel a need to persuade people that scientists are actually fun-loving and cool?  Perhaps the only sure way of not appearing cool is for adults to try to explain to a young person just how cool they are. Obviously, using the word ‘cool’ so often makes it abundantly clear that I am certainly NOT cool.  ‘Serious’ professions like medicine, law, or business do not try to persuade people that their careers are fun.  If you don’t believe me then try a simple exercise.  Do a Google Image search for ‘science’, and then for ‘law’ or ‘business’ or ‘medicine’.  As a hint, one set of images is dominated by cartoons, the other three are not.

I also cringe when I see science programmes on TV aimed at younger people, often with ‘zany’ presenters showing how science can be so much fun.  Let me quote from a 2015 Sunday Times TV review of an Irish science programme. ‘Silliness in the name of science was a recurring feature of [programme name omitted], a series that veered wildly between the youthfully exuberant and the childishly skittish….  Science TV (presenters) have been supplanted by giddy MCs who seem capable of speaking only in a cheerleading register’.  As a contrast, David Attenborough is the ultimate science presenter, never talking down to his audience, never dumbing down difficult ecological concepts, but retaining a genuine enthusiasm and deep knowledge of his subject.  He is never fun, but his message is clear and engaging.

Surely it is more important to communicate just how important science is to modern life and invite the next generation to join in, rather than to emphasise science as a fun career.  How could you get up every morning to a fun job?  You would go mad within a few weeks.  I have never found science to be fun.  I have found it to be challenging, frustrating, exciting, exacting, rewarding and infuriating in equal measures.  If you regard being the first person in human history to learn something new about our universe as ‘fun’, then so be it.  I would rather characterise it as a humbling and thrilling experience.  We should be clear in our messaging.  Scientists conceived and created the world we live in.  We (the computer scientists and physicists) made possible the smartphone or laptop upon which you are almost certainly reading this.  You may well only be alive because of medical interventions such as antibiotics provided by us (the chemists and biologists) and you can only be fed in such large numbers as a result of our efforts (animal and plant scientists, food scientists).  Why then do we feel a need to claim ‘science is fun’ in order to attract the brightest and best young people into science?

This blog is aimed both at science communicators and scientists alike.  We work in the most important career of all, in the only profession that can ensure a future for our race and our planet.  We have the most important roles in all of human activity – discovering and understanding our universe.  So let’s try again with a new message to attract the brightest and the best – “Science is hard, but that is exactly what makes it worth doing”.

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Academics working with industry  

by Dr. Colin Hill, APC Microbiome Ireland & School of Microbiology, University College Cork, Ireland

Many scientists have reservations about working with industry.  While characterising it as going over to the dark side might be an overstatement, there is a certain wariness that principles may have to be compromised (in terms of the ambition of the work and the freedom to follow your nose that is the supposed hallmark of ‘pure’ research), dull routine work may have to be performed, and publication in the best journals will be unlikely.  There may also be concerns that students or post-docs working on ‘industry’ projects may suffer from these constraints, which will restrict their career development.  There can also be a perception that the ‘best’ scientists work on fundamental problems, unfettered by the demands of industrial partners or short-term commercial goals.  Some of you reading this opening paragraph may be amused at the simplicity of this stereotyping  – “no one really thinks like that” – but I can assure you that some do, including a younger version of myself.

I have only really worked closely with industry in the last decade.  Before that, I wrote grants which assured potential funding agencies that what I wanted to investigate was incredibly relevant and important, would represent good value for the taxpayers’ investment, but was just a ‘little bit too early’ for industry to take on.  I genuinely believed this for the most part, although part of getting older is learning that fooling myself has always been a much easier task than fooling anyone else.  Nonetheless, I managed to forge a career in science.  I had a reasonable success rate of about one in four or five applications, which still seemed a poor return for the effort involved.  I would take my hard-earned funding and do my best to deliver on the promises I had made.  On occasion, the grants were successful, and we ended up filing a patent or developing a prototype or a process and essentially delivering on the promises made in the grant application.  But all too often I discovered that what we had achieved, or the problem we had solved, was not really the burning issue I had thought it to be, or at least could not be translated for the benefit of society without suitable industry partners.  In essence, we had self-tasked ourselves to solve a problem that no one really needed to be solved (or, at least not yet, or not in the precise manner we had solved it).

Of course, on occasion I was successful in getting truly ‘fundamental’ or ‘basic’ grants which were simply aimed at generating knowledge, and these were absolutely vital in developing new skills and opening up new research areas and possibilities.  However, over the past decade or more, I have begun to work closely with industry partners.  At first, this was driven by changes in funding policy in Ireland which linked scientific excellence to industry relevance – grants had to pass rigorous peer-reviewed scientific assessment, but also had to be validated by an industry partner willing to put skin in the game in the form of co-funding.  This necessitated finding industry partners and identifying a research problem together, before developing a solution.  I hope that now I have a perspective on both aspects of scientific research – often simplistically referred to as basic versus applied research – and I have good news.  Working with industry can be just as scientifically rewarding as not working with industry.

As I have experienced it, working with industry has several obvious advantages.

  1. Relevance. You know the research problem posed is one that genuinely needs solving, and the industrial partner for any solution you may develop is already engaged.
  2. Funding. Once you begin to work with an industry partner, the prospect of getting funding is much higher than in most competitive grant applications and the amount available may be defined by the extent of the problem, not the limit of a particular funding call.
  3. Intellectual capital. Most of the industry people you will be dealing with are also scientists, and they are just as clever, or far cleverer, than you (or me).  They will have defined goals but also have the same scientific curiosity which can be harnessed within the project.
  4. Flexibility. If you have embarked on the project and you find you have gone down a blind alley, it is usually possible to have a discussion with your partners and change the project design.  You don’t have to go back to the funders for permission to adjust the dreaded Gantt chart and ‘deliverables’, or have to justify to grant reviewers why you have gone off track. If a project extension is required you can often simply argue for it, no need to write a new grant and experience the inevitable downtime ‘between funding’.
  5. Urgency. Working with a student or a post-doc on a problem can be exciting, but sometimes a good or a bad result seems important only to the two of you.  It really adds urgency when an industry meeting is looming on the horizon, when you know the funders are directly invested in the outcomes of the experiments, and when the pressure really builds on the team.  In these moments some intense brainstorming and problem-solving can be required, which can create a real sense of excitement within the project and which can be a tremendous learning experience for junior members of the team.
  6. Career development. Most of the students and postdocs in the lab will not end up in academia, nor should they.  It is valuable training for young scientists to have a first-hand exposure to industry-based science so that they can make an informed choice on their next step in their career.

Are there negatives?  Well, honestly, not all industry sponsored research involves cutting edge science.  But if you are completely uninterested in the outcomes then don’t take it on.  What about bias?  Does industry funding create a bias towards positive outcomes?  I genuinely have not found this to be the case.  Reputable industry partners have no interest in biased results, since the company’s reputation is at stake and of course, no one is more invested in the scientific validity of their product than the industry partner.  And given that science is ultimately self-correcting no reputable scientist wants to be associated with misleading outcomes.  Individuals on either side can make mistakes or display bias, but that is no less true in the basic sciences.

The ideal academic-industry relationship recognises that there have to be rewards for both partners.  For both it is really important that the experiments be conducted to the highest possible standards with appropriate controls.  For the academic the right to publish the results in a timely fashion is particularly important when junior scientists are involved and a clear understanding of how results will be disseminated must be reached before the collaboration gets underway.  For the industry partner, it is important that the work stay focused on the agreed goals of the project and not veer off into the ‘nice to know’ rather than ‘need to know’ areas of the research problem.  As in most things, problems can be avoided by having a clear agreement on the goals, methods and publication strategy and having transparent reporting structures. Further, both sides must put effort into maintaining a good working relationship.

Finally, it is not a binary choice – working with industry obviously does not close off any other type of research you may want to perform.  You can still write grants and get funding from other sources.  In fact, I would propose that the ideal research mix requires an element of exploratory science to keep the laboratory fresh and industry-funded science to ensure relevance.  And when in doubt always defer to the great Louis Pasteur, who said “There are no such things as applied sciences, only applications of science”.

reid probiotics definition

You’d think we’d know probiotics by now

Prof. Gregor Reid, PhD MBA, Lawson Research Institute, University of Western Ontario, Canada

When I took my MBA, it was primarily to understand business and its relationship with science. I thought I learned quite a lot, but some things puzzle me to this day. Marketers know that messages are more effective when repeated. But, a guy called Thomas Smith (maybe related to Scotland’s famous Adam Smith who pioneered political economy, whatever that means!) wrote a guide in 1885 (yes that long ago!) called “Successful Advertising,” that noted:

The 1st time people see or read something, they don’t see it.
The 2nd time, they don’t notice it.
The 3rd time, they are aware that it is there.
The 4th time, they have a fleeting sense that they’ve seen it before.
The 5th time, they actually read the ad.
The 6th time, they thumb their nose at it.
The 7th time, they get a little irritated with it.
The 8th time, they think, “Here’s that confounded ad again.”
The 9th time, they wonder if they’re missing out on something.
The 10th time, they ask their friends or neighbors if they’ve tried it.
The 11th time, they wonder how the company is paying for all these ads.
The 12th time, they start to think that it must be a good product.
The 13th time, they start to feel the product has value.
The 14th time, they start to feel like they’ve wanted a product like this for a long time.

This goes on and on. It made me think about the definition and interpretation of probiotics. The version published in 2001 through two large respected organizations (WHO and UN FAO) has pretty much been universally accepted, and again reiterated in 2014 in a highly prestigious journal. That article is widely cited, so you’d think people would get it, right? They’d know what a probiotic is and what it’s not, right?

Yet, I speak at events around the world, and the same things keep coming back. Whether it is the 6th or 7th response (thumbing noses or being a little irritated) or a speaker confidently talking about probiotics and getting most of it completely wrong, I have scratched my head to the point my hair is falling out (a good research topic if someone would like to investigate this correlation). I even told a first year dentistry class of 55 students three times that the definition of probiotics would be an exam question. Only 8 got it correct!

I went back to the literature, as all scientists do, and asked the question “Why can’t people see what’s right in front of them?” It turns out either they believe you don’t have the answer, or you can’t have the answer, or you can’t have the answer right here and now, or they believe the answer needs to look like something else. This has a name – it’s called a schotoma – which seems appropriate, like people taking a shot at probiotics, or taking a shot at defining it, or providing their version of what it is.

With my hair now almost as thin as Glenn Gibson’s, I’m at a loss. Probiotics are not dead, not undefined/unstudied fermented foods, not in you unless you’ve taken them, not synonymous with “acidophilus”. They don’t typically colonize and they don’t have to be isolated from a human to work for humans. Products with lots of strains or a huge dose are not necessarily better products.

If you want to find the right probiotic for you, too often your doctor or health shop worker doesn’t give the best advice, because they haven’t read the articles. You should go www.usprobioticguide.com or www.probioticchart.ca and find something suitable for your needs. If you want some good general guidance, check out ISAPP infographics and ISAPP videos. If you are a company, don’t call your product a probiotic unless the contents have been tested in humans at the dose you are delivering at end of shelf-life. Call it strains of lactobacilli or something along those lines. Not being on one of these charts might be a sign that you’ve not done the needed work to call your product a probiotic.

But hey, maybe you need to read Thomas Smith’s guide. Probiotics are really quite simple. But, then again it’s only the hundredth time I’ve said that.

As for prebiotics, I’ll let someone else go bald on that one.

probiotics association of india

ISAPP Goes to India

By Mary Ellen Sanders PhD and Dan Merenstein MD

ISAPP sent two key-note speakers to the Probiotics Association of India meeting, held Feb 16-17 in New Delhi. Prof. Dan Merenstein MD spoke on “Evidence for clinical indications: how do probiotics measure up?” and Dr. Mary Ellen Sanders addressed “Is it time for live cultures to be included in official dietary recommendations?”  Dr. Merenstein also gave a second talk on an ISAPP-supported project:  the evidence that probiotic consumption can reduce antibiotic utilization. This is the 3rd PAi meeting that ISAPP has supported through speaker sponsorship.

The meeting featured talks on synbiotics to prevent late-term sepsis (Pinaki Panigrahi), the impact of diet on the Indian gut microbiome (Yogesh Shouche), autism (Sheffali Gulati) and 10 selected student/young investigator presentations on diverse microbiota/probiotic studies. Because of the high quality student presentations, judges were unable to choose the best to award prizes. The solution: all 10 presentations were awarded 5000 INR, supported by Prof. Pinaki Panigrahi’s Center for Global Health and Development. A poster session and original probiotic-themed drawings (see below for one submission) were also presented.

Dr. Sanders also spoke on “The contribution of probiotics to health” in an event held February 15 sponsored by the Gut Microbiota and Probiotic Science Foundation (India). This event was attended by ~150 professionals in nutrition, medicine and microbiota/probiotic research.

Of course, the trip was not all work. Below, Mary Ellen takes a selfie with her new elephant friend, Sampa.

probiotic poster

Probiotics and Good Gut Health. An artistic interpretation by a student, Simranjeet Singh.

elephant india

Mary Ellen Sanders takes selfie with Sampa, a 62-year old Asian elephant.

probiotics larson photo

Probiotics: the importance of the complete product

February 11, 2018. By Dr. Olaf F.A. Larsen, Assistant Professor (0.2 FTE) at Athena Institute, VU University Amsterdam, The Netherlands, and Science Manager at Yakult Netherlands.

Probiotics are, according to the WHO and later updated by a consensus panel convened by ISAPP, defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. Most scientific literature ties probiotic properties to individual strains, although evidence suggests that some health benefits may generalize to the species or genus level. Another important factor in how a probiotic performs is the type of matrix (e.g., a milk drink) that carries the probiotic. Indeed, many successful commercial probiotic products are largely defined by both the probiotic contained and the final product format. A plethora of probiotic products are available, ranging from fermented milks/yogurts, cereal products, juices and freeze-dried products (powders and pills). Some products claim to be probiotic but lack substantiation, such as “probiotic” pizzas and mattresses. It is likely that the probiotic properties are not solely determined by the probiotic strain itself, but also by the harbouring matrix. Hence, in order to fully understand the parameters that drive functionality of a specific probiotic, the total product should be evaluated.

Recently, the influence of the matrix on measures of probiotic functionality was reviewed. The data suggest that the matrix impacts several parameters, including number of viable probiotic microorganisms present in the product through shelf life and survival of the probiotic through the gastrointestinal tract. As an example, the number of viable microorganisms in the product as a function storage time can be profoundly different depending on the combination of probiotic strains and matrices used. Some products in which lyophilized probiotics are incorporated into a peanut butter matrix can have storage times up to 50 weeks. Whey proteins present in milk may improve gastrointestinal tract survival. Therefore, one should be aware that it is likely that viability of the probiotic will be impacted by the carrier matrix.

Another way that matrix can be important is through delivery of additional beneficial substances. For example, milk products contain various vitamins, calcium and high quality protein. In the case of a fermented probiotic product, the fermentation process may yield functional substances such as antihypertensive peptides. These effects can be considered as “additional benefits” of the matrix, beyond the impact of matrix on probiotic survival both in the product and in your body.

The body of scientific evidence falls short, however, of proving the importance of matrix on health endpoints. For a given amount of probiotics delivered, we lack comparative studies that prove that the end-benefit of one carrier matrix is better than another. Many supportive studies suggest that this will be the case, but until head-to-head human studies are conducted, we don’t know for sure.

Given the impact the matrix exerts on probiotic survival, and the possible effect on probiotic effectiveness, keep in mind the importance of efficacy studies conducted on the complete probiotic product. We need more research to fully understand the role of matrix on probiotic effectiveness, but the strongest evidence comes from studies conducted on the complete probiotic product.

Figure: Determinants of probiotic product parameters (adapted from Flach et al. 2017). Mark B. van der Waal is gratefully acknowledged for producing the artwork.

probiotics larson photo

 

For another perspective see Does the delivery format affect probiotic efficacy?, March 28, 2018 by Mary Ellen Sanders.

Talking Science with ISAPP’s Science Translation Committee

By Christopher Cifelli, PhD, VP of Nutrition Research, National Dairy Council.

Communicating with others is an essential part of everyday life. We are constantly sharing information about a variety of topics with friends, family, and even strangers. Most of the time the interaction is easy and natural – and sometimes even fun. But, have you ever talked to a scientist or asked a scientist a question?

Scientists love to talk about their research. And, other scientists want other to know about their research. They enjoy expounding on the minute details of their work and can spend hours on the littlest detail. That is one trait that makes a scientist effective – the attention to detail needed to posit hypotheses and then experimentally test them in controlled, thought-out manners. Scientists can talk to other scientists easily – but, ask some of them to explain their work to the average person and it doesn’t always go so well.

ISAPP is composed of scientists that are world-renowned experts on probiotics, prebiotics, and fermented foods. And, like other scientists, ISAPP wants others to know and understand these complex topics so that they can make informed decisions that may benefit their health. The question was – how does ISAPP do that? The answer: focusing on effectively translating the science. I offered ISAPP my leadership of a new committee to take on this task. ISAPP formed the Science Translation Committee nearly 3 years ago with a goal of taking complex scientific topics and making them easy to understand for consumers and health professionals. The result of this effort has been the development of numerous infographics, blog posts, and informational videos that translate years of research into easily digestible nuggets of information that people can use. The most recent infographic focused on dispelling some common myths about probiotics – because, who doesn’t like some myth busting!

Effective science communication is essential – essential because it can help people understand the complex and enable them to make choices that can benefit their overall health. ISAPP – which is grounded in science – will continue to be the voice of probiotic and prebiotic science and work to help people understand these fun and interesting topics. So, check out our website and our resources and start learning!

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Global FoodOmics: A Crowd-Sourced Window Into Microbes In Our Foods

January 25, 2018. By Mary Ellen Sanders, PhD , Dairy & Food Culture Technologies

Among the factors under our control, diet may be the most important determinant of our gut microbiota. Observations from the American Gut Project suggest that foods containing live microbes increase fecal bacterial diversity, which is generally associated with a healthy gut.

An initiative, Global FoodOmics, was launched earlier this year at the University of California San Diego under the auspices of the American Gut Project to learn more about bacteria in foods and the small molecules they produce. Dr. Julia Gauglitz is the project manager. Food samples (over 2000 have been collected to date) have been analyzed for their small molecule composition and will be tested by 16S rDNA sequencing to determine the bacterial species present. Although currently in its early stages, the aim for this project is to inventory the vast different foods consumed by people around the world.

Although many fermented foods (beer, bread, wine, kefir, many cheeses and others) rely on yeast or molds as fermentation or ripening agents, this project will aim to detect bacterial DNA, but these DNA approaches cannot distinguish between life and dead bacteria.  Labels and other descriptors accompanying submitted food samples may help determine if the species detected are likely to be alive. Fermented foods that retain live bacteria are more likely to influence our colonizing microbiota.

The small molecules being assayed are not limited to the ones produced by microbes. They may be due to microbial growth in the food (by food fermentation microbes or perhaps by spoilage or food poisoning microbes), may be innate to the food, or may be intentional or incidental (e.g., pesticides) additives to foods.

The intent is to turn Global FoodOmics into a crowd-sourced project. It will join the American Gut Project as an avenue for citizens to directly participate in science and enable the project to make all of the data publically available to other researchers and clinicians.

It is notable that this project is not the first attempt to understand the microbial components of food. Food microbiologists for decades have been assaying foods for microbes used to produce food, responsible for food spoilage and linked to food poisonings.  Recently, Prof. Bob Hutkins, University of Nebraska, on behalf of the International Scientific Association for Probiotics and Prebiotics (ISAPP) and with support from the National Dairy Council, embarked on a project to learn the state of knowledge about levels of live microbes in fermented foods. They dug into the published literature and emerged with “A survey of live microorganisms in fermented foods”, In Press at Food Microbiology. This paper gives us a summary of what is known about populations of live microbes in fermented foods, information that is very useful for people wanting to add live microbes to their diet.

Another effort to understand microbes in foods is the Consortium for Sequencing the Food Supply Chain, a partnership between IBM Research and Mars Inc. This project, focused on food safety, aims to develop a baseline of normal microbial communities in foods.

Both Global FoodOmics and the Consortium for Sequencing the Food Supply Chain will leverage modern DNA sequencing technologies to allow us better understand the microbes associated with foods. Global FoodOmics is the first project to understand the microbes and molecules in foods, by pairing small molecule metabolomics measurements with rDNA sequencing.

blog reid elderly

Do dietary effects on gut microbiota promote health in older individuals? Reid and colleagues gain insights into microbiota composition across the lifespan

January 22, 2018. By Dr. Gregor Reid

ISAPP Board of Directors member Dr. Gregor Reid recently co-authored a cross-sectional study in a cohort of over 1000 very healthy Chinese participants from 3 to over 100 years of age in order to gain insights on ‘healthy’ microbiota composition and whether this changes with age. Using next-generation sequencing (Illumina MiSeq platform) and large-scale compositional data analysis techniques, the study demonstrated that there was very little difference in the fecal microbiota composition of individuals between the around 30 years of age and around 100—as long as the individuals were extremely healthy.

The concept of consuming live microorganisms that offer a benefit to the host (probiotics), or a substrate that is selectively utilized by host microorganisms conferring a health benefit (prebiotics), to promote health in aging populations is becoming more popular. However, it is not currently known what constitutes a ‘healthy’ gut microbiota composition, or what specific prebiotic/probiotic might help establish it.

Discussing the study results in a Reddit Ask Me Anything session, Reid explains, “It is hard to pin down outcomes to one factor such as food, and which components of those foods are critical, but seeing the super-healthy elderly having the same microbiota profile as the super-healthy young adult might make us see if some food practices from 75 years ago have returned.”

Although the study design (cross-sectional) does not allow for a cause and effect relationship to be established, the results may signify that the similarity of gut microbes across ages is a consequence of an active lifestyle and good diet—in contrast with previous hypotheses that aging per se affected gut microbiota composition. Based on these findings, it is reasonable to hypothesize that reestablishing a dysbiotic microbiota composition in older adults, to mirror that of a 30-year-old, may promote health. Moreover, the results offer an established baseline microbiota composition by which other cohorts with chronic or acute disease may be compared.

blog post resilience figure 1

Resilience as a measure of health: implications for health claims for foods

January 16, 2018. By Mary Ellen Sanders PhD, Sylvie Binda PhD, Seppo Salminen PhD, Karen Scott PhD

Demonstrating health benefits for healthy people is a challenge faced by those attempting to communicate claims on a health promoting food. Foods, in many global regulatory frameworks, are intended for the general population. Therefore, any benefits ascribed to them, the logic goes, must be demonstrated in the generally healthy population.

An old concept has new-found notoriety in the context of offering an approach for establishing health benefits for healthy people. It is the concept of resilience. In an ecological sense, resilience refers to the ability of an ecosystem to withstand perturbation and continue normal function, i.e. maintain homeostasis. In the context of human physiology, resilience enables a host to remain healthy even when exposed to a stress, or to recover from a stress faster. A variety of external challenges such as drugs, pathogens, emotional stress, poor diet among others, may perturb normal physiological function or disrupt the gut ecosystem. Individuals more able to maintain stability of physiological functions when exposed to such challenges would be healthier than those who cannot maintain stability.  Thus, a food would be considered to have a beneficial effect if it could increase the resilience of the consumer to a challenge.

This concept was described in an EFSA guidance document on biological relevance of data in scientific assessments:

“When subject to a disturbance, a biological system enters in a transient state: a process variable has been changed and the system has not yet reached steady state. Some systems, including humans, have the capacity to regulate their internal environment and to maintain a stable, relatively constant condition of properties; it is called ‘homeostatic capacity’. Resilience represents the amount of disturbance that can be absorbed by a system before the system changes or loses its normal function, or the time taken to return to a stable state, within the normal operation range following the disturbance…” [Reducing] “homeostatic capacity … might be detrimental, whereas increasing the capacity could be beneficial.”

This concept aligns with the definition of ‘health’, which includes the ability to adapt to the environment.

Resilience of gut microbiota

This concept of resilience can be applied to the human microbiota as an ecosystem. Once established in early childhood, our colonizing microbiota reaches a relatively stable state. Although brief fluctuations occur, especially in relation to daily diet and medicines used, the microbial ecosystem of a healthy adult provides relatively stable functionality.  Disruption of the microbiota by repeated stressors can be associated with poorer health. There seems to be a solid rationale that the ability of the colonizing microbiota to resist, or recover quickly from, perturbations reflects a person’s ability to remain healthy. The microbiota stability may be indicated in either populations of bacteria or their metabolic output.

Homeostasis and health: a statistical approach

“A statistical approach to measuring improved health was proposed by Dr. Dan Tancredi at the 2010 ISAPP meeting. It is reprinted here from: Sanders, et al. 2011. Health claims substantiation for probiotic and prebiotic products. Gut Microbes 2:3, 1-7.

An approach to measuring improved health may be to measure homeostasis, as suggested by D. Tancredi. From a statistical point of view, if an intervention were able to minimize the variation around the mean for a specific measure (even in the absence of changing the mean; Fig. 1), it could be a reflection of improved health, assuming a biological rationale exists that tighter control of the parameter is physiologically advantageous. In other words, lessening the fluctuation around an individual’s biomarker could be interpreted as contributing to improving health. This novel idea emphasizes the importance of homeostasis as a focus of studies on health, and provides a rationale based in solid statistical theory as a way to measure this.

One challenge to demonstrating the value of this approach is to identify appropriate biomarkers that could be studied. The following properties would be important to a relevant biomarker for homeostasis:

blog resilience figure one

  • maintaining moderate levels of the biomarker is associated with good health;
  • high or low values are associated with ill health;
  • biomarker levels in the same person can fluctuate over time; and
  • reducing the magnitude or duration of such fluctuations in healthy people is considered desirable (Fig. 2).

Such a biomarker could be an individual endpoint or be formed as a ratio of two other biomarkers, when maintaining the same relative amounts of the two component biomarkers would be desirable.

Assuming a biomarker with the above properties is available, it could be used as the outcome measure in a randomized controlled trial to provide evidence that the experimental food is able to improve the maintenance of health in humans. Statistically, the trial would be set up to address the hypothesis that the experimental substance is associated with lower variation in biomarker levels, compared to the control arm, in subjects who were healthy at baseline. Such a trial would be able to use information on within-person variations in biomarker levels, even those who did not become ill. Partly as a result of the more efficient use of study data, such a trial would require far fewer subjects than an intervention that instead addressed the hypothesis that treatment is associated with fewer healthy persons becoming ill.

A mounting understanding of the value of stability of the colonizing microbial communities makes this endpoint an attractive one to consider. Perturbation of gut microbiota is associated with intestinal dysfunction, as illustrated during antibiotic treatment. Specific probiotics have been shown to promote a quicker rebound from antibiotic-induced microbiota disruption, including a study on Lactobacillus rhamnosus GG (LGG) (Cox et al. 2000). This paper concludes ‘…that a key mechanism for the protective effect of LGG supplementation on the subsequent development of allergic disease is through the promotion of a stable, even and functionally redundant infant gastrointestinal community.’

However, it would be useful to define additional biomarkers that would be appropriate targets for this type of investigation.

In pediatric nutrition, the measurement of metabolic homeostasis has become a standard approach when developing infant formulas (Heird, 2005).  The concept of homeostasis as a model to distinguish between foods (including food supplements) and medicinal products was explored by the Council of Europe (2011), and is an interesting correlate to the above hypothesis.”

Conclusions

The recent recognition by EFSA that maintenance of homeostasis is a valid measure of health provides an opportunity to apply this concept to validate health benefits of specific foods and food ingredients. Stability of microbial populations, microbial metabolism or host physiological readouts could be measured to reflect the concept of resilience. Since there is no definitive composition of a ‘healthy human microbiota’, a more reasonable target for measuring positive impacts of a probiotic on the microbiota would be reflected not in absolute levels of specific microbes but in the ability of a specific probiotic or prebiotic to bolster the resilience of the microbiota.

 

References:

Council of Europe. Homeostasis, a model to distinguish between foods (including nutritional supplements) and medicinal products 2008; (Accessed February 24, 2011, at http://www.coe.int/t/e/social_cohesion/soc-sp/homeostasis%20%282%29.pdf ).

Cox MJ, Huang YJ, Fujimura KE, Liu JT, McKean M, Boushey HA, et al. Lactobacillus casei abundance is associated with profound shifts in theGunderson LH, 2000. Ecological resilience: in theory and application. Annual Review of Ecology and Systematics, 31, 425–439.

EFSA guidance document:  Guidance on the assessment of the biological relevance of data in scientific assessments; July 12, 2017; EFSA Journal 2017;15(8):4970

Heird WC. Biochemical homeostasis and body growth are reliable end points in clinical nutrition trials. Proceedings of the Nutrition Society 2005; 64:297-303.

Huber M, Knottnerus JA, Green L, van der Horst H, Jadad AR, Kromhout D, Leonard B, Lorig K, Loureiro MI, van der Meer JW, Schnabel P, Smith R, van Weel C, Smid H (2011). “How should we define health?” BMJ. 343:d4163.

Sanders, et al. 2011. Health claims substantiation for probiotic and prebiotic products. Gut Microbes 2:3, 1-7; May/June 2011

 

 

 

 

 

 

 

 

 

watch with times they are a-changin quote by bob dylan

The Times They Are A-Changin’ With Probiotics

December 15, 2017. By Prof. Daniel Merenstein, MD, Department of Family Medicine, Georgetown University Medical Center, Washington DC.

I had a surprising encounter a few weeks ago in the clinic. I was caught off guard, had to take a step back and think about what happened. I recommended to my patient that she take a probiotic with the antibiotic I was prescribing. She said to me, “What is a probiotic?” My response was, “A probiotic,” as if it didn’t require any further explanation. It was nearly incomprehensible to me that she didn’t know what a probiotic was and maybe she just didn’t hear me or just didn’t understand me (I tend to speak too fast). But no, she just didn’t know what one was. I then realized how unusual this encounter was.

Something has been a-changing. It hasn’t been a quick process and I am not sure when it changed, but it did. Even just a few years ago when I recommended supplementing a course of antibiotics with a probiotic, people were generally receptive and had a vague idea about probiotics. However we generally had to talk about what probiotics were and how to use them. Fast forward to today and it appears to me that 95% of people respond, “I already take one.” Much more common than hearing “What’s a probiotic?” is to hear, “Of course, you always have to take a probiotic when taking an antibiotic.”

I am currently recruiting for my 8th probiotic clinical trial (PLAY ON). My team has recruited over 1,400 participants for previous studies. We have a system and a great team, but we are having the most difficult time recruiting for this study. I have thought a lot about why and I think it comes down to the times they are a-changin’. When we started on this research path 12 years ago, our research team and the subjects we recruited were excited about probiotics and their potential. But today the public doesn’t see the potential of probiotics; they know probiotics impact the gastrointestinal tract and should be used when taking antibiotics. Therein lies our challenge: to be in our study a subject has to be willing to take the chance of being in the placebo group. That makes little sense to a public that already knows to take a probiotic when on antibiotics.

My first two NIH studies were funded by the National Center for Complementary and Integrative Health, while my current study is funded by the National Institute of Child Health and Human Development. The shift has occurred from complementary, to mainstream. One need no longer attend a microbiome or probiotic conference to hear talks on probiotics; nearly all clinical conferences will now have probiotic talks. I am confident my team will adjust to these changing times but I think more important is how researchers and clinicians adjust. Probiotics are not alternative options anymore, the evidence base is robust and some indications well-studied. The discussions need to shift from, “You should have probiotics on formulary” to specific recommendations of which probiotics should be used for what indications. Similarly when discussing other disease states in the gut (e.g. necrotizing enterocolitis, infantile colic, and irritable bowel syndrome), it is time to take the next step and discuss specific recommendations. I am sure I will see another patient who has never heard of probiotics, but I’m willing to bet that doesn’t happen for many months. More likely, I expect I will be discussing the efficacy of the products my patients are already taking. That is an important change that docs need to think about.

Come gather ’round people
Wherever you roam
And admit that the waters
Around you have grown
And accept it that soon
You’ll be drenched to the bone.
If your time to you
Is worth savin’
Then you better start swimmin’
Or you’ll sink like a stone
For the times they are a-changin’.

Bob Dylan, Nobel Laureate

The Times They Are A-Changin’

Columbia Records, 1964

stethoscope and keyboard

Interpreting Risk Reduction in Probiotic & Prebiotic Clinical Trials

November 2017. By Prof. Michael Cabana MPH MD, Professor of Pediatrics, Epidemiology & Biostatistics and Chief, Division of General Pediatrics, University of California San Francisco.

Over the last few decades there has been a rapid acceleration in the number of published studies and clinical trials focused on probiotic and prebiotic interventions.  One common result that is reported is the change in risk of a condition or outcome after taking a probiotic or prebiotic supplement.  News articles and broadcasts commonly highlight claims in clinical trials (e.g., “this trial suggests a 33% reduction in X…).  However, in a world where news is sometimes transmitted in 140 characters or less, much nuance from a proper clinical trial can be lost. When assessing claims of risk reduction, it is important to evaluate and interpret these results in their proper context.  Here are a few tips.

What type of risk reduction is being reported?

When assessing the claims from a clinical trial, determine whether the claim is being presented as a relative risk reduction or an absolute risk reduction.  Sometimes the report may describe the risk of the outcome or disease directly compared to the normal incidence of the disease (i.e., incidence seen in the control group). This is a report of an absolute risk reduction. For example, if the control group had a 15% frequency of disease X and the probiotic group had a 10% frequency of disease X, then the absolute risk reduction is 5% (15%-10%=5%). Sometimes the report may describe a relative risk reduction, which is the % change between the risk in the probiotic group compared to risk in the control group. If the control group had a 15% frequency of disease X and the probiotic group had a 10% frequency of disease X, then the probiotic reduced your relative risk by 33% ([15%-10%]/15% = 5%/15% = 33%).

Is the risk reduction clinically significant?

If you notice that a relative risk reduction is being reported as statistically significant, you then need to ask yourself if the outcome is clinically significant. It is possible that a very large change in the relative risk reduction may not be clinically important. For example, if a probiotic intervention decreases the relative risk of disease X by 33%., this percentage sounds very impressive. However, if the baseline risk of contracting disease X is only 0.06% (e.g., it is a very rare condition), then the risk after the probiotic intervention is only 0.04% (still very rare, as reflected in the absolute risk reduction of 0.02%). Although the decrease of 33% that is reported as relative risk seems large, if you take into account the baseline risk, you realize that this is not clinically significant. The risk of 0.06% and 0.04% are essentially the same.

When evaluating an intervention, the context of the disease makes a difference. How often is this disease or condition occurring in the population being studied? The problem with reporting a relative risk reduction is that it is easy to overlook how common or uncommon the disease is to begin with.

Look for the “Number Needed to Treat”

One way to better assess the impact of an intervention is to calculate a “Number-Needed-to Treat” (NNT).  The NNT is the inverse of the absolute risk reduction.

From our example above, a 33% relative risk reduction of a condition with a prevalence of 0.06% (e.g., a very rare condition), means that the probiotic intervention had an absolute risk reduction of 0.02%. The NNT would be equal to 1/[0.0002]= 5000. This NNT of 5000 means that you’d need to treat 5000 patients with the probiotic intervention to change the outcome of only one patient.

Take a different scenario. If the disease was much more common (e.g, 9% prevalence) and the relative risk reduction was still 33%, then absolute risk reduction would be 3%. The NNT in this case would be equal to 1/(0.03)=33.3. This NNT of 33.3 means that you’d need to treat only 33 patients with the probiotic intervention to change the outcome of one patient. This treatment is much more likely to be meaningful in the population.

The NNT is a quick way for clinicians to evaluate an intervention to take into account the risk reduction in the context of the baseline risk.

Conclusion

When examining the results from clinical trials, just looking at percentage changes can be deceiving. Unfortunately, relative risk reduction often results in more sensational headlines, so beware of how the press, and even top quality journals, report study results. When assessing the clinical trial results in the context of clinical care, keep in mind how common or rare the disease is. Even a large percentage change may not make a big difference overall in patient outcomes if the initial risk was very low to begin with. Evaluate and interpret clinical trial results in their proper context.

salminen and hutkins at YINI

Fermented Foods in Nutrition & Health

November 2017. Discussed at International Union of Nutritional Sciences (IUNS) Congress session. By Prof. Seppo Salminen, Director of the Functional Foods Forum, University of Turku.

Recently, the Yogurt in Nutrition Initiative (YINI) convened a scientific session as part of the International Union of Nutritional Sciences (IUNS) Congress, held in Buenos Aires from October 22-27, 2017. The session focused on how yogurt and other fermented foods affect the composition and activity of the gut microbiota and health. Lectures covered microbiota development in humans, metabolic effects of yogurt and fermented foods, the role of fermented dairy foods on health, and the role of yogurt and fermented foods in nutritional guidelines

Professor Robert Hutkins and I presented at the YINI session. Dr. Hutkins spoke about “Health benefits of fermented dairy foods: microbiota and beyond” and started by defining the role of microorganisms during food fermentations. He then reviewed current research findings on the impact of fermented foods on the human intestinal microbiota. He also distinguished between the microbes that perform the fermentation and those added specifically as probiotics. Although they are often closely related, they are not the same. Both culture-based and molecular methods have shown that although microbes consumed in fermented foods often survive transit, they rarely persist after consumption has ended. Still, they may be able to modulate functional activity in the gut and, in the case of yogurt bacteria, improve tolerance to lactose.

My presentation was titled “Improving your diet with fermented foods: harmonizing dietary guidelines including fermented milks” and I reviewed the role of yogurt in dietary guidelines and recommendations in different countries along with the regulatory status of yogurt and health claims. The talk focused on existing guidelines in Europe; specifically, the live bacteria in yogurt and lactose intolerance claim approved by the European Food Safety Authority. This claim states that yogurt cultures improve lactose digestion (and tolerance) in individuals with lactose maldigestion. Additionally, I suggested that fermented dairy products should be included in dietary guidelines in a more consistent manner, as recommendations currently vary from country to country. A special focus was also given to an Argentinian social program which provides at present over 200,000 school children with locally produced yogurt with a probiotic to improve their health and well-being.

The role of fermented foods and especially yogurt has gained substantial attention among researchers, clinicians, public health workers, and consumers. In addition to the live organisms present in fermented foods, peptides and other metabolites produced by these organisms may also mediate important health benefits. Thus, cultured dairy foods and other fermented products may have important effects on public health and their consumption should be encouraged.

stool sample for lab

Microbiome Analysis – Hype or Helpful?

September 2017. By Karen Scott, PhD, Rowett Institute, University of Aberdeen, Scotland.

Since we have realized that we carry around more microbial than human cells, and that these microbial inhabitants are important to maintain our health, searching for the bacterial species that are implicated in causing disease has become the holy grail of microbiology. However, to understand which bacteria are unnaturally present or absent in a disease state, we first have to understand what constitutes normal. This is hampered by the fact that we are all different – and our microbial communities are also all different. In fact, the faecal bacterial community in samples taken months apart from one person will be identifiable as coming from that specific healthy adult, but the community will be quite distinct from samples from any other healthy adult. In the same way, the microbial community of two individuals suffering from the same disease will be different.

Despite these differences, scientists have managed to establish some facts over the past 15 years. Too many Proteobacteria, which includes Enterobacteria and E.coli, in your large intestine is not generally good news. Firstly, it means that conditions in the large intestine are probably not as anaerobic as they should be. Secondly, an expansion in these populations usually means a decline in something else – after all food and places to live are finite resources. Bacterial diversity in the adult intestine is also important. The main factor that has been found across many different diseases is that bacterial diversity is lower in diseased individuals than their healthy counterparts. This does not necessarily mean that a low diversity is causing the disease, as various features of the disease (including any antibiotic therapy, inflammation, decreased or increased transit time) may all themselves affect the diversity of the microbiota.

Although scientists have not succeeded in defining a ‘healthy microbiota,’ there is an increasing trend to get your microbiome tested. Entrepreneurial microbiome companies are bombarding us with offers to “send in a small sample and find out about your gut microbiota”. All of course, for a ‘reasonable’ price. So, should you?

This really depends why you want to know, and what level of detail of analysis is being offered. Remember the orders of taxonomy? Kingdom, phylum, class, order, family, genus, and species.  Some companies identify the bacteria in your faeces only to the phylum level. This is a taxonomic level above the level needed to differentiate mammals and fish (these are ‘classes’). If you told someone that there were more fish in the Indian Ocean than mammals would this be a surprise? It would be such an expected fact it would be meaningless. This is similar to describing the microbiota at a phylum level – Bacteroidetes numbers versus Firmicutes numbers. Such numbers are meaningless. However, continuing the fish analogy, if you said that there were more mackerel than tuna in the North Atlantic Ocean this becomes a bit more meaningful. The fisherman immediately knows what type of fish he is more likely to catch, and perhaps even which net to use. The same is true of the microbiome. Telling someone that he/she has a lot of Enterobacteria and few Roseburia is actually useful as we know from studies that this represents an abnormal balance of bacteria and something should be done to redress this. Yet the bottom line health consequence of this abnormal balance of bacteria remains to be determined. So getting your gut microbiome sequenced could be useful – depending on what level of information you will receive, and what you are prepared to do about it.

And so we come to the next problem. Having established what your gut microbiota is, how are you going to make it better? And will that make YOU better? At the moment scientists don’t really have a good answer to these questions. Specific prebiotics can certainly be useful to increase the numbers of some bacteria generally assumed to be beneficial – such as Bifidobacterium, Faecalibacterium prausnitzii and even Roseburia species. But it is not really clear what the exact health benefits of such an increase in bacterial numbers would be. Health claims on prebiotics are currently limited to ‘improve intestinal transit’ and ‘lower the glycaemic response’. If you found out that your microbiota had a low diversity, increasing the variety of foods in your diet, in particular the fibre component, could certainly improve this. Our gut microbiota basically relies on our undigested food to survive, so providing a greater amount and more types of food containing fibre and prebiotics will definitely encourage populations of diverse bacteria to expand. In addition to improving digestive health, fibre fermentation by gut bacteria also results in the production of microbial products that have been shown to have health benefits.

So by all means get your gut microbiome analyzed if you want to, but perhaps instead, save your money and just increase your prebiotic and fibre consumption, which will increase levels of the potentially beneficial bacteria that are already there in your gut.

brain-gut relationship illustration

Bugs on the Brain: the Microbiota-Gut-Brain Axis

September 2017. By Eamonn M. M. Quigley, Chief Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Professor of Medicine, Weill Cornell Medical College, Houston, Texas, USA.

We can all remember those instances of diarrhea (or at least frequent bowel movements) and “butterflies” that we suffered before a critical test, interview or presentation. These are examples of stress originating from the brain influencing gut function. Extensive research over the past several decades has revealed that this is a two-way street – the gut constantly signals to the brain, too. This bidirectional channel of communication between the “big brain” in the cranium and the “little brain” (i.e. the enteric nervous system) in the gut came to be referred to as the gut-brain axis. This link relies on neurons of the sympathetic and parasympathetic nervous systems, as well as circulating hormones and other neuromodulatory molecules.

We now understand that mental symptoms of stress, anxiety or depression have a clinical impact on the gut. These include situations where the brain, the gut and their channel of communication, the autonomic nervous system, are affected by the same pathologic process. Parkinson’s disease is a prime example. Indeed, a hypothesis has evolved to suggest that Parkinson’s disease actually originates in the gut and ascends to the brain. Other scenarios include those instances where neurologic symptoms are a consequence of a primarily gastrointestinal pathology. This occurs in malabsorption syndromes when nutrients such as folic acid and B12, which are critical to brain function, become deficient. Finally, and most commonly, are those situations such as irritable bowel syndrome (IBS) where it is widely believed that symptoms result from dysfunction or disturbance somewhere along the gut-brain axis. In some individuals the problem may lie primarily in the gut; in others the main issues may be a distorted representation of gut stimuli in the brain.

Recently the concept of the gut-brain axis has been extended to include the microbiota (the microbiota-gut-brain axis) and tantalizing evidence suggests that bacteria resident in the gut could have an impact on the “big brain”. Indeed, some researchers have raced ahead to suggest that assessing alterations in the microbiome could assist in the diagnosis of a host of neurological disorders and that therapies targeted at the microbiome could play a central role in disorders as diverse as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, autism, stroke, depression and drug addiction.

We should remember that the microbiota-gut-brain axis is far from a novel concept as it was clearly described over 60 years ago with research on hepatic coma. Metabolic products of gut bacteria lead to this much feared complication of advanced liver disease and an intervention targeted at the microbiome, namely, the administration of antibiotics, was shown to be dramatically effective. In these pioneering studies the role of bacterial overgrowth in the small bowel by coliforms and other bacteria, which are normally confined to the colon, was found to be important. Subsequently, these same bacteria and the inflammatory response that they evoke have been incriminated in the pathophysiology of another common consequence of chronic liver disease, portal hypertension, as well as in other complications such as spontaneous bacterial peritonitis, systemic sepsis and hemostatic failure. Indeed, there are several manifestations of this tripartite resonance between microbiota, the liver and the central nervous system. Gut health factors such as small bowel bacterial overgrowth, an abnormal microbiota, impaired gut barrier function, a pro-inflammatory state and the appearance in the systemic circulation of neuro-active molecules generated by bacterial metabolism are all postulated to play important roles in the actual pathogenesis of a number of common liver diseases. So what is new?

From the basic science laboratories and a variety of animal models a pretty coherent message has emerged. Firstly, the microbiome can influence brain development, structure and function and lead to changes in cognition and behavior. Secondly, the manipulation of the microbiome – for example, with probiotics – can ameliorate certain brain disorders and reverse impaired function. Thirdly, the inoculation of microbiota samples from individuals with a number of neuropsychiatric disorders into animal models can recapitulate features of the human disease. So far so good.

As always, extrapolation from animal studies to humans is fraught with difficulties: differences between animal and human brains and microbiota, the limitations of animal models of psychiatric and functional bowel disorders, and, above all, the challenges of studying brain function in humans. The good news is that these challenges are being addressed. Researchers are utilizing various technologies that provide dynamic images of brain function in various parts of the brain in response to a variety of situations, stimuli and exposures. These are now beginning to provide evidence that our microbiota can influence brain function and that the gut microbiota might, indeed, be a therapeutic target for patients with disorders such as depression, Parkinson’s disease and autism. Data are preliminary and certainly not at a stage where we can offer diagnostic testing based on a fecal sample or recommend antibiotics, prebiotics, probiotics or fecal microbiota transplantation for a given neuropsychiatric disease or disorder. But watch this space!

kombucha

Kombucha: Trend or New Staple?

September 2017. By Prof. Bob Hutkins, Khem Shahani Professor of Food Science, University of Nebraska, Department of Food Science and Technology, Lincoln.

This blog post is adapted from a piece published by the Lincoln Journal Star. The article, first published May 4, 2016 and written by Prof. Bob Hutkins, appeared as a response to a reader’s question: “I keep hearing about kombucha… What is this stuff?”

Kombucha (pronounced kom-BOO-chuh) is made by fermenting sweetened tea using a combination of yeasts and bacteria. This mixture of live cultures that starts the fermentation is called SCOBY, short for “symbiotic colony of bacteria and yeast.” The SCOBY takes the form of a gooey mat that can be re-used for each batch or shared with friends.

Kombucha is one of many trendy fermented foods, like kimchi and kefir, that are now found everywhere. No longer just the fare of hipster cafes and posh restaurants, you can find kombucha at your local grocery store—or even at Walmart.

Kombucha’s origins go back at least 2,000 years, to China; the drink gradually spread throughout Asia and Europe. In the U.S., kits for home-brewing kombucha became available to consumers in the early 1990s, and bottled versions soon appeared on grocery store shelves.

Several factors may explain the popularity of kombucha. First, many people like the flavor: uniquely sweet and sour, with a vinegary overtone. Some ethanol (alcohol) may also be present, although commercial products must contain less than the legal limit of 0.5 percent. The fermentation reaction yields carbon dioxide, which gives kombucha a pleasant fizziness. Flavor combinations are endless, from ginger, mango, and blood orange to lavender and cinnamon.

It’s probably the suggested health properties that are most responsible for the kombucha craze. The live cultures in some blends have antimicrobial activity, which may have been valuable in past eras when antibiotics were not available. However, these properties depend on the particular mix of microbes, which varies from batch to batch or brand to brand. Other suggested health benefits range from improved gut health and digestion to treatment of cancer and other diseases. Unfortunately, there is no scientific evidence to support these health claims.

It may be that kombucha is not for everyone—the acidic nature of the drink may not sit well for some people. Microbiologists have also expressed concern that home-brewed kombucha could possibly contain toxin-producing fungi. (See related post on making safe fermented foods at home.)

Nonetheless, there’s no doubt that many consumers are drinking kombucha. Annual sales in the U.S. are over $500 million, with double-digit growth. Around half of the coveted 25-to-34 age group (i.e. millennials) are kombucha drinkers. Yes, it’s popular now, but it also seems that kombucha is likely to be around for a while.

 

Bob Hutkins is the Food Doc. He is a professor at the University of Nebraska-Lincoln, where he teaches and conducts research in food science and food microbiology. Questions on any topic related to food, food safety, food ingredients and food processing can be sent to the Food Doc at features@nulljournalstar.com.

bowl of yogurt with strawberries

Advice from a Nutritionist:  Eat More Fermented Foods.

September 2017. By Christopher Cifelli, PhD, VP of Nutrition Research, National Dairy Council.

Whenever I tell someone that I have a degree in nutrition science, I usually get asked, “Are carbs bad?” or “Should I avoid added sugars?” Rarely do I get asked “What should I be eating more of?” While vegetables, fruits, dairy and whole grains would all be perfectly suitable answers to that question, my go-to response is fermented foods.

Fermented foods have been around for thousands of years. Fermentation is the process of using specific microbes – for example, bacteria, yeast, and molds – to transform one food into another. For example, the fermentation process transforms milk into yogurt. Fermented foods are unique because they can contain live microbes, which can confer health benefits beyond simple nutrition. For instance, did you know that the microbes in fermented foods can help inhibit pathogen growth in the gut? Or, that eating certain fermented foods, such as yogurt, is associated with reduced chronic disease risk?

Government organizations across the globe provide dietary recommendations to help guide people choose the type of foods or diets that promote health. Commonalities include eating more fruits, vegetables, whole grains, beans, legumes and dairy. Another commonality – albeit a disconcerting one – is the lack of a recommendation for consuming fermented foods even though fermented foods, including red wine, kimchi, soya, and yogurt are key parts of healthy diet patterns.

Several recent publications have discussed the need to encourage the consumption of foods that can directly and beneficially impact our gut microbiota to improve overall health (e.g., Bell et al. or Gordon et al.). Identifying and consuming foods that can selectively impact the microbiota to benefit the host health should be a priority.

The time is now. Health professionals should review available evidence to determine how fermented foods fit into dietary recommendations to promote a healthy microbiota. They should encourage the public to increase their consumption of fermented foods to support the health of their microbiota and body. That way, the next time any of us are asked “What should I be eating” we can point to dietary recommendations and say — Fermented Foods!

Read more on fermented foods here and here.

Bacteria illustration

Suggestions for Making Safe Fermented Foods at Home

September 2017 – By Drs. Bruno Pot and Frédéric Leroy, Vrije Universiteit Brussels, Brussels, Belgium.

The impact of lifestyle on the composition and diversity of the human gut microbiota over the last five decades has been tremendous. This is thought to be mainly the result of a cumulative effect ascribed to the increased use of antibiotics and other drugs as well as dietary changes, including consuming less fermented foods that contain live microorganisms.

Fermented foods are important for a healthy diet, as they have the potential to improve the microbiota quality and diversity, are related with reduced disease risk, and can provide essential nutrients.  Consumers are constantly being informed about these benefits, leading to pleas for a return to home-made fermented foods. However, there is rarely mention of the risks that home-made natural fermentations can entail. While making fermented foods at home can be a good idea and help you consume more beneficial microbes, we should realize that the empirical knowhow, skills and equipment to make safe food fermentations may have disappeared over time. This blog is a gentle warning about the possible risks of non-controlled fermentations.

  • Use a starter culture: The use of specific starter cultures at sufficiently high concentration is recommended to properly initiate the fermentation of specific foods and to obtain sufficient control over the process. Relying on spontaneous fermentation (i.e., hoping that environmental bacteria or yeasts initiate the fermentation) increases the risk that uncontrolled fermentations by unsuitable bacteria, yeasts and molds will result in bad or variable quality. In the worst case, dangerous end-products will be obtained.
  • Twice is nice: Starters should not be used repeatedly. Because bacteria multiply several times per hour, their genetic material is changing continuously and the quality of the starter will change over time. It is therefore not a good idea to re-use your ‘old’ product to restart a ‘new’ fermentation all too often, although some fermented food ecosystems such as sourdough or water kefir may usually be ‘backslopped’ frequently. The risks are that off-flavours will be formed or that acidification, which protects your food against the growth of spoilage or pathogenic bacteria, will be too slow.
  • Choose wisely: Not all starters are necessarily safe, although commercially available ones should in principle have been checked for safety (See Helpful Information links below for guidance on findings the right starter). Some yeasts and lactic acid bacteria (LAB) can form compounds (for example, biogenic amines from amino acids) that can result in many health troubles like headache, blood pressure drops, diarrhoea, and even heart problems. You can avoid the production of biogenic amines by using selected starters that do not have the metabolic machinery to make them.
  • To breathe or not to breathe: Some fermentations, like the production of water kefir (usually using dried figs), should be performed in the absence of air and thus require a rubber sealing. For other fermentations, a complete submerging in brine or a covering with oil is necessary. Kombucha, on the contrary, needs a wide opening covered by a cloth that allows oxygen into the vessel. Uncontrolled anaerobic conditions can increase the risk for the growth of clostridia. In cheese making they can be the cause of cheese blowing up, in other conditions they may produce the deadly botulin toxin.
  • Avoid Moulds. Moulds are another problem linked to (too much) oxygen. Moulds can make mycotoxins which can make one very sick and any visible contamination should ring bells! It is not wise to scrape them off, as often they have produced toxins already, left spores or will remain present through their ‘roots’ which most of the time are not visible.
  • Hold the alcohol: During fermentation, sugars are converted to lactic and acetic acids, but also to ethanol. Therefore, the concentration of sugar added may impact the final alcohol levels of the end-product.
  • Pass the gas: In the case of water kefir, the use of a water lock can be necessary, as the CO2 gas which is formed during the fermentation may increase the pressure in the vessel, leading to potential breaking or surprises during opening. Therefore, blown fermented foods products should never be consumed.
  • Party crashers and acid balance: Not all bacteria are your friends. Some undesirables can be present on fresh vegetable products and can in themselves lead to spontaneous fermentation. Therefore, it is important to not let your fermentation be hijacked by these bacteria. The good bacteria should grow and produce acid quickly for a safe fermentation. Pathogens generally cannot grow in high acid environments (below pH 4 is a safe target). This acidity should be reached as quickly as possible during fermentation to avoid the growth of bacteria which can produce toxins or off flavours.
  • Nothing lasts forever: While high acid is essential, it does not protect the food indefinitely. Some yeasts and fungi can grow in high acid. As they grow, some can reduce acidity locally so that (mainly at the surface) other (potentially pathogenic) bacteria can develop
  • Use good quality raw materials. Use only good quality and fresh ingredients when deciding to ferment. While fermentation helps to preserve your fresh foods longer, it will not rescue (almost) spoiled products!
  • Summer and winter milk. If you use milk in your fermentation, it is also possible that the quality of the end product will be different along with the season, as summer milk, harvested from cows in the field, has a different composition from milk harvested from cows fed winterfeed.
  • Temperature. Temperature control is important. While for sauerkraut room temperature 18-22 (65-72°F) is fine, yoghurt fermentation is much better at 37°C (100°F). You, therefore, can expect differences in summer and winter if you do not control the temperature. Find the right spot in the house for both summer and winter.
  • Water activity. In addition to acidification, microbial control is often achieved by reduction of the water activity, generally by sufficient salting and/or drying. This is of major importance to produce fermented sausages. It is important to point out that raw meat is a particularly hazardous matrix, requiring even more care and attention when performed at home.
  • Salt and acetic acid (vinegar) concentration. Both ingredients help keep the pathogens at bay. Stick to recipes that have proven to be reliable.
  • Fermentation time. This is an important factor which can vary a lot and, in turn, impact the quality of your end product. Its critical nature is well known from wine making, in which the duration of the primary and secondary fermentation is well known to be crucial to the quality of the result. While in wine the primary fermentation usually takes between 3 to 7 days, the secondary fermentation can take much longer and will depend on the vial, the alcohol concentration and the yeast used. The fermentation of sauerkraut goes in three stages. ALL three are essential for a safe and tasteful product; a minimum of three to four weeks is necessary. Industrially produced yoghurt can be made in 8 hours, but at home it may take a few hours more. How much more again depends on the milk quality, the starter and the temperature.
  • Do’s and don’t’s: Do invest in a kitchen weighing scale and a thermometer that goes from 0 – 100 °C. Don’t even think about home-made sausage.  Don’t even think about raw-milk cheese.  Do start with simple foods like yogurt or kefir.  There are fool-proof kits for making beer (although they require some hardware).  Sauerkraut and kimchi are relatively easy to make.

Being aware of these simple concepts can help ensure the production of a healthy, tasty fermented food. Consumers should expect that the quality of the resulting fermented food will vary from lot to lot and they should be able to judge when a product is still safe for consumption and when it is not. Consumers should also be aware of the risk factors above and know how to select and handle equipment and execute procedures that will yield safe and nutritious end products.

For additional information:

Fermented Foods on the www.ISAPPscience.org website.

Preparing Fermented Foods and Pickled Vegetables

The University of Georgia Cooperative Extension, the National Center for Home Food Preservation

Safe Preserving: Fermented Foods From the University of Wisconsin Extension

ISAPP Annual Conference photos

ISAPP – Going beyond the science at our annual meetings.

June 2017. By Prof. Glenn Gibson, The University of Reading, UK.

Having never wrote a blog in my life (nor sent a twit nor Instamatic-gram nor facial networking book message), I had to consult my social media savvy children on what this blogging business was all about and who cares anyway. Both looked at me with exasperation, as if I had just crawled out of a cave, and gave me the highly informative answer “Write about what you want, you luddite, but try to make it less boring, than normal. If you write it, then it should perhaps be called clogging not blogging.”

What you might call a total vote of no confidence; anyway it did get me thinking. If this blog was for the ISAPP website, then surely it must have to at least mention probiotics and prebiotics – but that is what I have written about each day for as long as I can remember, and none of that ever had any impact! So, if you are reading this expecting to be educated on bugs, guts, health, faeces, etc, then please do move along to your next Google page.

When I think about what ISAPP has done differently, the science springs to mind, but then there has also been our annual meeting and the associated “fun” (for some people anyway….) activities that have been a hallmark. So, here is my reflection on these. This is all from my-  rapidly fading – memory and all mistakes are my own. I apologise if you have never attended ISAPP and hope that the below text does not discourage you from ever doing so!

It all began in London, Ontario in May 2002 with a treasure hunt in the woods and various ball games (remember, all delegates take part in these exercises). Bob Rastall eventually emerged as the winner and came out of the nearby woods clutching his hard earned treasure like it was a golden fleece. Actually it was a cuddly teddy bear – pink I think, to match his eyes. To this day, he still brags to students about the riches that can be gained with perseverance and unstinting application – as well as several pints of cold drink before tackling the task.

Next year, it was off to Henley UK for the epic Team Probiotics vs Team Prebiotics cricket match. Perhaps about 1% of participants fully understood the rules. Highlights included the Americans pitching the ball like a baseball (known as a beamer in cricketing parlance and highly illegal); Willem de Vos taking mobile phone calls while fielding at deep mid-wicket (which as you know is equidistant between deep square leg and cow corner but at the opposite side of the wicket to cover, point and extra cover i.e. 45o from mid on and fine leg); various attempts to catch the ball with one hand while clutching a full beer in the other; me being out for nothing (a duck) to the worse ever ball bowled in cricket history; the Americans (again) dropping the bat when running. As befitting a game that can last for 5 whole days, a draw was declared.

2004 saw us in the dizzy heights of Copper Mountain resort in Colorado. Here, the fun event took on added sophistication with a GPS driven game and various tasks to be completed. Have you ever seen over 100 highly trained scientists trying to master a small electronic gadget? (think Keystone Cops on amphetamines). Mary Ellen and family were the official adjudicators with Rick being introduced by her as “the nearest thing I’ll get to a secretary.” Gregor’s late night turn in the bar as a hybrid between Dave Lee Roth and one of the Supremes was not to be missed either.

On to Coleraine, Northern Ireland for a tour of the local attractions, including the spectacular Giants Causeway and Carrick-a-Rede rope bridge. Next, was London UK for an open meeting in 2007 where we were entertained by Jimmy Bright the professional comedian. He won over the notoriously tough scientific audience with his tales of British eccentricities and foibles – at least true for those who understood his accent.

The only venue to have hosted ISAPP twice is London, Ontario to where we returned in 2008. The social event here was a user friendly guide to social media by Amber MacArthur. Almost a decade later I write my first blog – well, these things do take time.

In 2009, we visited Newport Beach, California. Here, we hosted a joint meeting with NAS Sackler and therefore had to be on our best behaviour (for proof of this see the image). One highlight was seeing dolphins in the wild from Newport pier.

It was back to sporting excellence in 2010 at Castelldefel. Lots of Spanish family Sunday afternoons were completely ruined by the entire ISAPP descending on their beach for games, loudness and hilarity. This included football (Gregor acting as referee and goalscorer), volleyball, sand pictionary, quiz. Team Black Cats triumphed (had to mention that).

The next meeting was in Berkeley, I was not there so have no thoughts on the social prowess of the conference, but I did hear rumours of broken buses.

Cork in October 2012 featured a distillery trip and céad míle fáilt or póite (a hundred thousand hangovers). The next one in 2013, was joint with New York Academy of Sciences and featured one of the best views ever from a lecture hall. We also took time for a night boat trip on the Hudson.

Aberdeen was our location in 2014 for a joint meeting with the Rowett Institute of Nutrition and Health and INRA. Full scientific humiliation was evident at the Scottish Country Dancing event.

Georgetown, Washington had the ISAPP experience in 2015. This featured a once in a lifetime visit to the National Academy of Sciences for a posh dinner, and many contrived poses in the lecture auditorium.

Last year, we visited Turku, Finland and were transported back to the 1600’s for a medieval banquet hosted by Duke John and Princess Katherine, including the use of bread as a plate.

The 2017 meeting is almost upon us and we turn our mixture of science and fun towards Chicago. There is to be a bowling and beer event. Who knows what will happen, it won’t be pretty but it will definitely be competitive and, hopefully, memorable.

Goodness knows what new humiliation lies ahead for Singapore in 2018?