Hear from ISAPP board members in upcoming webinar covering probiotic and prebiotic mechanisms of action

New probiotic and prebiotic trials are published all the time – but when they show a health benefit, what do we know about the basic science behind it?

To provide insight into this topic, ISAPP has partnered with the International Life Sciences Institute (ILSI) Europe on a free webinar titled Understanding Prebiotic and Probiotic Mechanisms that Drive Health Benefits. This webinar will help scientists, members of the public, and media take a deep dive into what we know about the mechanisms of action of probiotics and prebiotics.

The webinar will take place on Thursday, September 17, 2020 from 3 – 4:15pm Central European Time. Registration is required here.

Short, 10-minute perspectives will be provided by the following top experts:

  • Prof. Sarah Lebeer, University of Antwerp, Belgium
  • Prof. Colin Hill, University College Cork, Ireland
  • Prof. Karen Scott, University of Aberdeen, UK
  • Prof. Koen Venema NUTRIM School of Nutrition and Translational Research in Metabolism, Venlo, The Netherlands

The presentations will be followed by a 35-minute live Q&A session, enabling participants to probe deeper into the science behind mechanisms of probiotics and prebiotics.

ILSI Europe is a non-profit organization that aims to improve public health and well-being from a science-based approach.

To learn more about probiotic mechanisms of action in advance of the webinar, see ISAPP’s blog post here.

New publication addresses the question: Which bacteria truly qualify as probiotics?

Although the international scientific consensus definition of probiotics, published in 2014, is well known—”live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”—the word is often used incorrectly in practice.

A recent article published in Frontiers in Microbiology builds on this definition and describes four criteria for accurate use of the word ‘probiotic’. Eight scientists co-authored the paper, including two ISAPP board members. The project was initiated by industry scientists affiliated with IPA Europe.

The authors explain why it’s important for scientists and companies to be sure the four identified criteria apply before using the term ‘probiotic’. Given the many misuses of the term that are evident today, however, consumers need to scrutinize ‘probiotic’ products to be sure they are legitimate.

Read the ISAPP press release on this publication here.

 

 

Early career researchers discuss the future of probiotics and prebiotics in the first ISAPP-SFA paper

By Irina Spacova, ISAPP-SFA 2019 President and postdoctoral fellow at the University of Antwerp, Belgium

Early career scientists play a vital and dynamic role in research, especially in environments supporting their enthusiasm and drive for innovation. ISAPP has long been promoting young researchers through its Students and Fellows Association (ISAPP-SFA), which is a student-led branch of ISAPP established in 2009. The SFA was championed and guided from its inception through June 2020 by Prof. Gregor Reid. Together with ISAPP, the organization encourages diversity and participation through free memberships and ISAPP meeting travel grants open to all students and fellows working in research institutions. Currently, ISAPP-SFA includes 450 members from 50 countries in Asia, Africa, North and South America, Europe, and Australia.

The 2019 ISAPP meeting in Antwerp, Belgium was a milestone for ISAPP-SFA participation with 48 early career attendees from 19 countries. Facilitated by discussion clubs and poster sessions, the Antwerp meeting created an exceptional ‘melting pot’ of ideas. It was clear that young researchers had a lot to say, and the lingering idea of creating the first ISAPP-SFA paper finally took shape during the ISAPP 2019 dinner cruise of the Antwerp Harbor.

Less than a year later, the paper “Future of probiotics and prebiotics and the implications for early career researchers” was accepted in Frontiers in Microbiology, just in time for the 2020 ISAPP meeting. This initiative was driven by the ISAPP-SFA 2019 executive committee members Irina Spacova, Hemraj Dodiya, Anna-Ursula Happel, Conall Strain, Dieter Vandenheuvel, and Xuedan Wang. The core of the paper reflects what we as early career researchers believe are the biggest opportunities and challenges in advancing probiotic and prebiotic science, and summarizes a wide array of promising in vitro, in vivo and in silico tools. We emphasize the important goal of using probiotics and prebiotics to ameliorate global issues, and give examples of current initiatives in developing countries, such as Westernheadseast.ca and Yoba4Life.org. Our advice for early career researchers is to form inter-connected teams and implement the diverse toolsets to further advance the probiotics and prebiotics field.

We had a lot of fun with this paper, but also several challenges. It was not trivial to produce a concise paper with many opinions, techniques and references that would be useful to both young and established researchers. This intercontinental endeavor between young scientists working in Belgium, Japan, Ireland, South Africa, USA, and UK required a lot of early-morning and late-night meetings. Many interactions and discussions were necessary to deliver a novel perspective to add to the many excellent reviews on probiotics and prebiotics already published. Accessibility of the publication was a decisive factor, and one of the reasons why we chose to publish open access in Frontiers in Microbiology. Of course, this publication would not be possible without ISAPP, and we are especially grateful for the input and encouragement from Gregor Reid and Mary Ellen Sanders.

ISAPP’s popular educational videos now feature subtitles in multiple languages

ISAPP’s series of six English-language videos are a useful resource for helping consumers answer important questions about probiotics, prebiotics, and fermented foods. In order to make these popular educational videos accessible to a wider global audience, ISAPP has now updated them with subtitles in multiple languages: Dutch, French, German, Indonesian, Italian, Japanese, Russian, and Spanish.

Dr. Roberta Grimaldi, a principal clinical research scientist who served as ISAPP’s Industry Advisory Committee representative from 2017-2019, led the video subtitling efforts.

“The videos are a good way to communicate information about these products, which are still not fully understood by consumers,” says Grimaldi. She says that while consumers see “a lot of miscommunication and misleading information” online, the easy-to-understand ISAPP videos help bring the scientific perspective to a broad audience.

Multi-lingual members of the ISAPP community stepped up to help with the translations, with Grimaldi managing the task and co-ordinating with the video production agency. She says, “It was definitely an amazing team effort, which I think gave us really great results.”

Science Translation Committee head Dr. Chris Cifelli underlines how worthwhile the video subtitles project has been for ISAPP. “Since ISAPP is an international organization, we have been working hard to make our educational materials accessible to as many people as possible. The subtitles allow the information in these videos to be shared much more widely, ultimately helping consumers make more informed decisions about probiotics, prebiotics, and fermented foods.”

Many of ISAPP’s infographics are also available in multiple languages.

 

How to change the language subtitles on an ISAPP video:

Step 1 – On the ISAPP videos page, click on the video.

Step 2 – Press pause and click the gear-like ‘Settings’ icon, to the right of the ‘CC’ icon.

Step 3 – Click on ‘Subtitles’ and select the language subtitle you prefer.

Step 4 – Resume the video by pressing play.

ISAPP welcomes three new board members

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

ISAPP is pleased to announce that Profs. Kelly Swanson PhD, Daniel Tancredi PhD, and Gabriel Vinderola PhD have joined the ISAPP board of directors. The expertise of these three globally recognized academic experts complements that of the current board members, together comprising a leading global group of distinguished scientific and clinical experts in the fields of probiotics, prebiotics, synbiotics, fermented foods, and postbiotics.

Read more about ISAPP’s newest board members:

Kelly Swanson is the Kraft Heinz Company Endowed Professor in Human Nutrition, a professor in the Department of Animal Sciences and Division of Nutritional Sciences and an adjunct professor in the Department of Veterinary Clinical Medicine at the University of Illinois at Urbana-Champaign. He is an expert in the field of fiber and prebiotics, and brings to ISAPP knowledge of application of these substances to companion and agricultural animals. Kelly, who trained with previous ISAPP Board member, George Fahey, is considered one of the top authorities in animal gut health, microbiome, and nutrition. His research has focused on testing the effects of nutritional intervention on health outcomes, identifying mechanisms by which nutrients impact gastrointestinal microbiota, host gene expression, and host physiology. Kelly served on the prebiotic consensus panel (here), led the ISAPP synbiotics consensus panel, and is lead author on the synbiotics outcome paper, currently in press with Nature Reviews Gastroenterology and Hepatology.

Dan Tancredi is a biostatistician with an appointment as an Associate Professor (full professor starting July 1, 2020) in Residence at UC Davis Department of Pediatrics, and is also with the Center for Healthcare Policy and Research. Dan works extensively on NIH-sponsored research and as an NIH scientific reviewer. He has an extensive record of collaboration with ISAPP; he has served as an invited expert and/or speaker at all but one ISAPP meeting since 2009, providing his perspectives on how to improve the quality and scientific impact of probiotic trials and how to conduct systematic reviews that rigorously and transparently synthesize the evidence from these trials. He has been a co-author on 6 ISAPP papers (here, here, here, here, here, here and here), including a 2020 paper “Probiotics as a Tx Resource in Primary Care” published in the Journal of Family Practice (see New publication gives a rundown on probiotics for primary care physicians). Dan was invited to author the Nature commentary on the landmark probiotics trial by Panigrahi, et al. for reducing newborn sepsis in the developing world—showing his reputation as a trusted voice for assessing the quality of probiotic research.

Gabriel Vinderola is a professor at National University of Litoral, Santa Fe, Argentina and Principal Researcher at CONICET, at the Dairy Products Institute (UNLCONICET). He is an expert in lactic acid bacteria, fermented foods, and probiotics. Gabriel has forged academic collaborations with academic and industrial scientists in numerous countries in Europe and with industrial colleagues in Argentina. He has been active in several countries in South America working with regulators to assure that their actions on probiotic guidelines are science-based, including his recent efforts consulting on guidelines for probiotics for the Codex Alimentarius. He has written blogs for ISAPP, translated ISAPP videos and infographics into Spanish, and was an expert on the ISAPP consensus panel on postbiotics. His research has focused on technological aspects of probiotics (biomass production, dehydration, storage, food matrices) and fermented foods. He is an active public science communicator in Argentina on the topics of probiotics, prebiotics, fermented foods, and the microbiome. See Growing interest in beneficial microbes and fermented foods in Argentina for some examples. Gabriel represents the first ISAPP board member from South America and we anticipate his involvement will help ISAPP expand its presence and connections in Latin America.

 

ISAPP partners with British Nutrition Foundation for fermented foods webinar

Did you miss the live webinar? Access the archived version here. Read the speaker Q&A here.

From sourdough starter tips to kombucha flavor combinations – if you’ve checked a social media feed lately, you’ll know how many people are sharing an interest in fermented foods as they self-isolate during the pandemic. And with this rise in popularity comes a host of questions about the practice and the science of fermented foods.

To meet the need for science-based information about fermented foods, ISAPP has partnered with the British Nutrition Foundation (BNF) on a free webinar titled ‘Fermented Food – Separating Hype from Facts.’ The BNF is a UK-based registered charity that brings evidence-based information on food and nutrition to all sectors, from academia to medicine.

The webinar, designed for practicing dietitians and nutrition-savvy members of the public, featured three leading scientific experts who explained the microbiology of fermented foods, the evidence for their health effects, and who might benefit from making these foods a regular part of the diet. Viewers will come away with a clear understanding of what fermented foods are and what evidence exists for their health benefits.

The webinar was held live on Wednesday, July 1, 2020 from 1pm-2pm (BST).

Webinar speakers & topics

 Understanding fermented foods: Dr. Robert Hutkins, University of Nebraska, USA

Exploring the evidence for effects of fermented foods on gastrointestinal health – how strong is it? Dr. Eirini Dimidi, Kings College London

What role can fermented foods have in our diet? A public health perspective, Anne de la Hunty, British Nutrition Foundation

For a quick primer on fermented foods, see the short ISAPP video here or the ISAPP infographic here.

New publication gives a rundown on probiotics for primary care physicians

With an increasing number of patients becoming aware of the human microbiome and its role in health, primary care physicians are faced with questions about probiotics as a possible strategy for maintaining health. Patients may see conflicting messages in the news and on product labels – so how can they know which probiotic benefits are scientifically proven?

A new publication in the Journal of Family Practice provides a quick update on evidence for the use of probiotics in different indications, so primary care physicians can equip themselves to provide evidence-based recommendations and to answer patients’ most commonly asked questions about probiotics.

Written by ISAPP board members Daniel J. Merenstein, MD and Mary Ellen Sanders, PhD, along with Daniel J. Tancredi, PhD, the article provides practical advice in the form of practice recommendations, along with comments about safety data from numerous clinical trials.

As Dr. Merenstein stated, “We wrote this article for working clinicians. They are interested in the science but are busy and want a straightforward evidence-based resource. We are hopeful this will be a go-to resource during the busy clinic day.”

Verbatim from the article are the following practice recommendations:

  • Consider specific probiotics to prevent antibiotic-associated diarrhea, reduce crying time in colicky infants, and improve therapeutic effectiveness of antibiotics for bacterial vaginosis.
  • Consider specific probiotics to reduce the risk for Clostridioides (formerly Clostridium) difficile  infections, to treat acute  pediatric diarrhea, and to manage symptoms of constipation.
  • Check a product’s label to ensure that it includes the probiotic’s genus, species, and strains; the dose delivered in colony-forming units through the end of shelf life; and expected benefits.

The full text can be accessed by logging into Medscape.

How some probiotic scientists are working to address COVID-19

By ISAPP board of directors

With the global spread of COVID-19, the scientific community has experienced an unusual interruption. Across every field, many laboratories are temporarily shuttered and research programs of all sizes are on hiatus. Principal investigators around the world are doing their part to keep their students and local communities safe, and many are donating lab safety equipment to medical first responders who urgently need it.

In this global circumstance of research being put on hold, it is enlightening to consider what some scientists in the fields of probiotics, prebiotics, and fermented foods are working on—or proposing—in the context of understanding ways to combat viral threats. These individuals are rising to the scientific challenge of finding effective ways to prevent or treat viral infections, which may directly or indirectly contribute to progress against SARS-CoV-2.

Here, ISAPP shares words from some of these scientists—and how they have connected the dots from probiotics to coronavirus-related work with potential medical relevance.

Prof. Sarah Lebeer, University of Antwerp, Belgium: Relevance of the airway microbiome profile to COVID-19 respiratory infection and using certain lactobacilli to enhance delivery or efficacy of vaccines

Could the microbes in our upper and lower airways play a role in how we respond to the virus? Significant individual differences exist in the microbes that are prevalent and dominant in our airways. Lactobacilli are found in the respiratory tract, especially in the nasopharynx. They might originate there from the oral cavity via the oronasopharynx, but we have found some strains that seem to be more adapted to the respiratory environment, for example by expressing catalase enzymes to withstand oxidative stress. Currently we have a Cell Reports paper in press that shows certain lactobacilli are more prevalent in the upper respiratory tract of healthy people compared to those with chronic rhinosinusitis. Further investigation of one strain found in healthy people showed it inhibited growth and virulence of several upper respiratory tract pathogens. Our work on other viruses shows that certain lactobacilli can even block the attachment of viral particles to human cells. This raises the possibility that lactobacilli could be supplemented through a local spray to help improve defenses against the inhaled virus. Based on these data, we are initiating an exploratory study with clinicians and virologists on whether specific strains of lactobacilli in the nasopharynx and oropharynx could have potential to reduce viral activity via a multifactorial mode of action, including barrier-enhancing and anti-inflammatory effects, and reduce the risk of secondary bacterial infections in COVID-19.

Another line of exploratory research from our lab pertains to the delivery or efficacy of SARS-CoV-2 vaccines. Currently, many groups are rapidly developing vaccines, which predominantly use the viral spike S protein or its receptor-binding domain as antigen to induce protective immunity. We are exploring the potential of specific strains of lactobacilli with immunostimulatory effects as adjuvants for intranasal SARS-CoV-2 vaccination, or the potential of a genetically engineered antigen-producing organism for vaccine delivery.

At this year’s virtual ISAPP annual meeting, Dr. Karen Scott and I will also be leading an ISAPP discussion group called “How your gut microbiota can help protect against viral infections”. We will discuss previous work that has shown bacteria can have anti-viral effects. For many years, our colleagues, Profs. Hania Szajewska and Seppo Salminen, have studied a different virus, namely rotavirus, that causes acute diarrhea in children, and have found that Lactobacillus rhamnosus GG (new taxonomy Lacticaseibacillus rhamnosus GG) binds rotavirus and disables it, thereby blocking viral infection/multiplication. This may explain why this probiotic reduces the incidence and duration of acute diarrhea in children. Similar findings have been reported for specific probiotics and prebiotics and prevention of upper respiratory tract infections.

Prof. Rodolphe Barrangou, North Carolina State University, USA: Engineering probiotic lactobacilli for vaccine development

Between NC State University and Colorado State University (CSU) there is a historical collaborative effort aiming at engineering probiotics to develop novel vaccines. The intersection of probiotics and antivirals is the focus here with expressing antigens on the cell surface of probiotics to develop oral vaccines. The CSU infectious diseases center is very much fully operational and focused on COVID-19 now, and we recently received a research exception to open our lab for two individuals assigned to this NIH-funded project, and pivot our rotavirus efforts here to coronavirus. We are actively engineering Lactobacillus acidophilus probiotics expressing COVID-19 proteins to be tested as potential vaccines at CSU in the near future, as progress dictates.

Prof. Colin Hill, University College Cork, Ireland: The microbiome as a predictor of COVID-19 outcomes

We have recently proposed a project to examine oral and faecal microbiomes to identify correlations/associations between COVID-19 disease severity and individual microbiome profiles. If funded, we propose to analyse bacterial and viral components of the microbiome from three body sites (nasopharyngeal swabs, saliva, and faeces) in 200 donors and mine the data for biomarkers of disease risk and clinical severity. We will use machine learning to identify microbiome signatures in patients who contract the virus and remain asymptomatic, those who develop a mild infection, or those who have an acute infection requiring admission to an intensive care unit and intubation. This will enable microbiome-based risk stratification of subjects testing positive, and appropriate clinical management and early intervention, and prioritization of subjects for receiving an eventual vaccine.

Dr. Dinesh Saralaya, Bradford Institute for Health Research, UK: A live biotherapeutic product for targeted immunomodulation in COVID-19 infection

The COVID-19 pandemic presents an unprecedented challenge to our healthcare systems and we desperately require the rapid development of new therapies to ease the burden on our intensive care units. As well as its appropriate mechanism of action (targeted immunomodulation rather than broad immunosuppression), the highly favourable safety profile of MRx-4DP0004 makes it a particularly attractive candidate for COVID-19 patients, and may potentially allow us to prevent or delay their progression to requiring ventilation and intensive care.

The trial is a Phase II randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of oral Live Biotherapeutic MRx-4DP0004 in addition to standard supportive care for hospitalised COVID-19 patients. Up to 90 subjects will be randomised 2:1 to receive either MRx-4DP0004 or placebo (two capsules, twice daily) for 14 days. The primary endpoint is change in mean clinical status score as measured by the WHO’s 9-point Ordinal Scale for Clinical Improvement, while secondary endpoints include a suite of additional measures of clinical efficacy such as need for and duration of ventilation, time to discharge, mortality, as well as safety and tolerability. The size and design of the trial are intended to generate a meaningful signal of clinical benefit as rapidly as possible.

Drs. Paul Wischmeyer and Anthony Sung, Duke University School of Medicine, USA: Probiotics for prevention or treatment of COVID-19 infection

We are planning several randomized clinical trials of probiotics in COVID-19 prevention and treatment. These trials are based on multiple randomized clinical trials and meta-analyses that have shown that prophylaxis with probiotics may reduce upper and lower respiratory tract infections, sepsis, and ventilator associated pneumonia by 30-50%. These benefits may be mediated by the beneficial effects of probiotics on the immune system. The Wischmeyer laboratory and others have shown that probiotics, such as Lactobacillus rhamnosus GG, can improve intestinal/lung barrier and homeostasis, increase regulatory T cells, improve anti-viral defense, and decrease pro-inflammatory cytokines in respiratory and systemic infections. These clinical and immunomodulatory benefits are especially relevant to individuals who have developed, or are at risk of developing, COVID-19. COVID-19 has been characterized by severe lower respiratory tract illness, and patients may manifest an excessive inflammatory response similar to cytokine release syndrome, which has been associated with increased complications and mortality. We hypothesize that probiotics will directly reduce COVID-19 infection risk and severity of disease/symptoms. Thus, we are proposing a range of trials, the first of which will be:

A Randomized, Double-Blind, Placebo-Controlled Trial of the PRObiotics To Eliminate COVID-19 Transmission in Exposed Household Contacts (PROTECT-EHC). Objective: Prevent infection and progression of illness in household contacts/caregivers of known COVID-19 patients exposed to COVID-19 (who have a >20-fold increased risk of infection). We will conduct a multicenter, randomized, double blind, phase 2 trial of the probiotic Lactobacillus rhamnosus GG vs. placebo to decrease infections and improve outcomes. This trial will include weekly collection of microbiome samples from multiple locations (i.e. fecal, oral). This trial will utilize a commercial probiotic, delivering 20 billion CFU of Lactobacillus rhamnosus GG, and placebo.

We are currently developing protocols to study prevention and treatment of COVID-19 in a range of other at-risk populations including: 1) Healthcare providers; 2) Hospitalized patients; 3) Nursing home and skilled nursing facilities workers. We are seeking additional funding and potential collaborators/trial sites for this work, and encourage interested funders and collaborators to reach out for further information or to join the effort at: Paul.Wischmeyer@nullduke.edu and also encourage you to follow our progress and our other probiotic/microbiome work on Twitter: @paul_wischmeyer

Prof. Gregor Reid, University of Western Ontario, Canada: Documenting anti-viral mechanisms of certain probiotic strains

While our institute is now studying the cytokine storm in COVID-19 patients, the closure of my lab has meant I have turned to surveying the literature: Prof. Glenn Gibson and I have a paper published in Frontiers in Public Health stating a case for probiotics and prebiotics to help ‘flatten the curve’ and keep patients from progressing to severe illness. There is good evidence that certain orally administered probiotic strains can reduce the incidence and severity of viral respiratory tract infections. Mechanistically this appears to be, in part, through modulation of inflammatory responses similar to those causing severe illness in COVID-2 patients, and antiviral activity — which has not been shown against SARS-Co-V2 but has been documented against common respiratory viruses, including influenza, rhinovirus and respiratory syncytial virus. Improving gut barrier integrity and affecting the gut-lung axis may also be part of these probiotics’ mechanism of action. At a time when drugs are being tried with little or no anti-COVID-19 data, probiotic strains documented for anti-viral, immunomodulatory and respiratory activities should be considered for clinical trials to be part of the armamentarium to reduce the burden and severity of this pandemic.

Rapid, collaborative effort

As the world waits in ‘lockdown’ mode, continued scientific progress for coronavirus prevention or treatment is critically important. ISAPP salutes all probiotic and prebiotic scientists who are stepping up to pursue unique solutions. Addressing the important research questions described above will require a rapid collaborative effort, from obtaining ethical approval and involving medical staff to collecting the samples, to recruiting participants as well as experts to process and analyze samples. All of this has to be done in record time – but from our experience of this scientific community, it’s definitely up to the challenge.

ISAPP provides guidance on use of probiotics and prebiotics in time of COVID-19

By ISAPP board of directors

Summary: No probiotics or prebiotics have been shown to prevent or treat COVID-19 or inhibit the growth of SARSCoV-2. We recommend placebo-controlled trials be conducted, which have been undertaken by some research groups. If being used in clinical practice in advance of such evidence, we recommend a registry be organized to collect data on interventions and outcomes.  

Many people active in the probiotic and prebiotic fields have been approached regarding their recommendations for using these interventions in an attempt to prevent or treat COVID-19. Here, the ISAPP board of directors provides some basic facts on this topic.

What is known. Some human trials have shown that specific probiotics can reduce the incidence and duration of common upper respiratory tract infections, especially in children (Hao et al. 2015; Luoto et al. 2014), but also with some evidence for adults (King et al. 2014) and nursing home residents (Van Puyenbroeck et al. 2012; Wang et al. 2018). However, not all evidence is of high quality and more trials are needed to confirm these findings, as well as determine the optimal strain(s), dosing regimens, time and duration of intervention. Further, we do not know how relevant these studies are for COVID-19, as the outcomes are for probiotic impact on upper respiratory tract infections, whereas COVID-19 is also a lower respiratory tract infection and inflammatory disease.

There is less information on the use of prebiotics for addressing respiratory issues than there is for probiotics, as they are used mainly to improve gut health. However, there is evidence supporting the use of galactans and fructans in infant formulae to reduce upper respiratory infections (Shahramian et al. 2018; Arslanoglu et al. 2008). A meta-analysis of synbiotics also showed promise in repressing respiratory infections (Chan et al. 2020).

Mechanistic underpinnings. Is there scientific evidence to suggest that probiotics or prebiotics could impact SARS-CoV-2? Data are very limited. Some laboratory studies have suggested that certain probiotics have anti-viral effects including against other forms of coronavirus (Chai et al. 2013). Other studies indicate the potential to interfere with the main host receptor of the SARS-CoV-2 virus, the angiotensin converting enzyme 2 (ACE2). For example, during milk fermentation, some lactobacilli have been shown to release peptides with high affinity for ACE (Li et al. 2019). Recently, Paenibacillus bacteria were shown to naturally produce carboxypeptidases homologous to ACE2 in structure and function (Minato et al. 2020). In mice, intranasal inoculation of Limosilactobacillus reuteri (formerly Lactobacillus reuteri) F275 (ATCC 23272) has been shown to have protective effects against lethal infection from a pneumonia virus of mice (PVM) (Garcia-Crespo et al. 2013). These data point towards immunomodulatory effects involving rapid, transient neutrophil recruitment in association with proinflammatory mediators but not Th1 cytokines. A recent study demonstrated that TLR4 signaling was crucial for the effects of preventive intranasal treatment with probiotic Lacticaseibacillus rhamnosus (formerly Lactobacillus rhamnosus) GG in a neonatal mouse model of influenza infection (Kumova et al., 2019). Whether these or other immunomodulatory effects, following local or oral administration, could be relevant to SARS-CoV-2 infections in humans is at present not known.

Our immune systems have evolved to respond to continual exposure to live microbes. Belkaid and Hand (2016) state: “The microbiota plays a fundamental role on the induction, training, and function of the host immune system. In return, the immune system has largely evolved as a means to maintain the symbiotic relationship of the host with these highly diverse and evolving microbes.” This suggests a mechanism whereby exposure to dietary microbes, including probiotics, could positively impact immune function (Sugimura et al. 2015; Jespersen et al. 2015).

The role of the gut in COVID-19. Many COVID-19 patients present with gastrointestinal symptoms and also suffer from sepsis that may originate in the gut. This could be an important element in the development and outcome of the disease. Though results from studies vary, it is evident that gastrointestinal symptoms, loss of taste, and diarrhea, in particular, can be features of the infection and may occur in the absence of overt respiratory symptoms. There is a suggestion that gastrointestinal symptoms are associated with a more severe disease course. Angiotensin converting enzyme 2 and virus nucleocapsid protein have been detected in gastrointestinal epithelial cells, and infectious virus particles have been isolated from feces. In some patients, viral RNA may be detectable in feces when nasopharyngeal samples are negative. The significance of these findings in terms of disease transmission is unknown but, in theory, do provide an opportunity for microbiome-modulating interventions that may have anti-viral effects (Cheung et al. 2020; Tian et al. 2020; Han et al. 2020).

A preprint (not peer reviewed) has recently been released, titled ‘Gut microbiota may underlie the predisposition of healthy individuals to COVID-19’ (Gao et al. 2020) suggesting that this could be an interesting research direction and worthy of further discussion. A review of China National Health Commission and National Administration of Traditional Chinese Medicine guidelines also suggested probiotic use, although more work on specific strains is needed (Mak et al. 2020).

Are probiotics or prebiotics safe? Currently marketed probiotics and prebiotics are available primarily as foods and food/dietary supplements, not as drugs to treat or prevent disease. Assuming they are manufactured in a manner consistent with applicable regulations, they should be safe for the generally healthy population and can be consumed during this time.

Baud et al. (in press) presented a case for probiotics and prebiotics to be part of the management of COVID-19. Although not fully aligned with ISAPP’s official position, readers may find the points made and references cited of interest.

Conclusion. We reiterate, currently no probiotics or prebiotics have been shown to prevent or treat COVID-19 or inhibit the growth of SARSCoV-2.

 

Connecting with the ISAPP community: Continuing to advance the science of probiotics and prebiotics

By Mary Ellen Sanders PhD, executive science officer, ISAPP

On behalf of the ISAPP board of directors, I am reaching out to the ISAPP community to say we hope you are doing well and taking all the necessary steps in your local communities to remain healthy. At present, the global ISAPP community is physically distant but digitally close, and it is important for us to remain connected and strong.

ISAPP’s activities are as important as ever during this time of increased attention to health, and ISAPP is continuing to uphold its commitment to (1) stewardship, (2) advancing the science, and (3) working with stakeholders. Although our annual meeting, which some of you may have initially planned to attend, has been cancelled, other ISAPP activities are continuing or expanding as follows:

 

  • Building on an important topic for our annual meeting, ISAPP is working to develop a strategic approach to communicating the science on probiotics, prebiotics, fermented foods, synbiotics, and postbiotics.
  • The ISAPP board of directors is pleased that our founding board members, Profs. Gregor Reid and Glenn Gibson, have agreed to remain on the board until the 2021 meeting, in particular to help with long-range planning. New academic board members will also be elected, thereby expanding the board. Working together, we will bring fresh insights, strategies and global reach.
  • The board is considering how best to approach our cancelled meeting. In lieu of re-scheduling this year’s in-person meeting, we are planning to have virtual content covering some of the originally scheduled topics. Some discussion group topics will be carried over to the 2021 meeting, while others will be addressed virtually. We will communicate further on this soon.
  • Our newsletter will continue on a monthly basis.
  • Blog postings, which are aimed at either consumers or scientists, remain timely and popular – with new contributions posted on average every 2-3 weeks. Authored by board members and other experts in the field, these blogs provide a forum for opinions and observations on current issues and controversies as well as insights on global fermented foods, critical regulatory actions, and other relevant topics.
  • ISAPP filed comments on March 17 with the American Gastroenterological Association in response to their draft recommendations for probiotic use in GI conditions.
  • Spearheaded by former ISAPP IAC representative to the board, Dr. Roberta Grimaldi, ISAPP has subtitled several of the most popular ISAPP videos in different languages, including Dutch, French, Spanish, Russian, Japanese, Italian and Indonesian. The first of these should be posted by end of April.
  • The ISAPP-Students and Fellows Association has launched a blog program to provide perspectives by young scientists on issues of importance to the probiotic and prebiotic fields. They have also submitted a manuscript to Frontiers in Microbiology discussing a toolkit needed for their future in science: “Future of probiotics and prebiotics: an early career researchers’ perspective”.
  • Three consensus panels have been conducted since May of 2019. A manuscript arising from the synbiotics panel, chaired by Prof. Kelly Swanson, is in press with Nature Reviews Gastroenterology and Hepatology. The paper summarizing the consensus panel on fermented foods, chaired by Profs. Robert Hutkins and Maria Marco, is almost ready for submission to Nature Reviews Gastroenterology and Hepatology. A manuscript from the consensus panel on postbiotics, chaired by Prof. Seppo Salminen, is currently being written. All three papers are expected to provide clarity to the field with regard to definition of terms, current evidence for health benefits, and impact on stakeholders.
  • In addition to the three consensus panel papers in progress, several different ISAPP endeavors are at different stages of publication:
    • ISAPP vice president, Prof. Dan Merenstein, and executive science officer, Dr. Mary Ellen Sanders, worked with biostatistician and frequent ISAPP contributor, Prof. Dan Tancredi, to summarize evidence for clinical endpoints for probiotics, to be published in the Journal of Family Physicians. This paper, titled “Probiotics as a Tx resource in primary care”. The paper is currently in press.
    • Several ISAPP board members and other participants in a 2019 meeting discussion group recently submitted to Current Developments in Nutrition a paper titled “Dietary Recommendation on Adequate Intake of Live Microbes: A Path Forward”.
    • Marla Cunningham, the current IAC representative to the ISAPP board, has led an effort to compile results from the IAC Learning Forum from the 2019 ISAPP meeting on the topic of matrix effects impacting probiotic and prebiotic functionality. Manuscript in preparation.
    • Colin Hill and I represented ISAPP on a paper under review at Nutrients initiated by IPA-Europe titled “Criteria to qualify microorganisms as ‘probiotic’ in foods and dietary supplements”. This paper consolidates and fleshes out minimum criteria for use of the term ‘probiotic’ published by different groups, including the 2002 FAO/WHO working group, the 2014 ISAPP consensus paper on probiotics, and the 2018 ISAPP discussion group on global harmonization.
    • Glenn Gibson and Marla Cunningham are coordinating a paper titled “The future of probiotics and prebiotics in human health” as an output from their 2019 discussion group.

See here for all published ISAPP papers.

ISAPP board members, 2019 annual meeting

Messages about probiotics and COVID-19

With many conflicting and confusing health messages circulating during this global pandemic, including some criticisms of our field as well as some unsupported claims made by certain individuals and companies, ISAPP will remain an important touchstone for scientifically accurate information. Focusing on health effects is key to demonstrating probiotic and prebiotic efficacy, and we acknowledge that human studies are the ultimate measure of efficacy, but also, elucidating mechanisms of action help us understand how these interventions interface with the immune system and other mediators of health.  Currently, there is some evidence that certain probiotics/prebiotics can reduce the risk of viral infections (discussed in other blog posts here and here), but it is important to remember that they have not been studied specifically for COVID-19 prevention or treatment. This must be acknowledged when communicating with the wider community.

We greatly appreciate the continued support of our IAC members. The ISAPP Board, colleagues, and SFA will continue to chart a course forward in preparation for life after the pandemic. Our intent is to emerge from these experiences more connected and purposeful than ever. We welcome suggestions on how collectively we can endure and strengthen the science and communications that remain foundations of our field.

 

 

 

New names for important probiotic Lactobacillus species

By Mary Ellen Sanders, PhD, and Sarah Lebeer, PhD

The genus Lactobacillus was listed as the fifth most important category of living organism to have influenced the planet throughout its evolutionary history in a 2009 book, What on Earth Evolved?. From their central role in food fermentations around the globe to their ability to benefit health in their human and animal hosts, species of Lactobacillus have great importance in our lives.

But for the past several decades there’s been a problem brewing with this genus. Using the research tools available at the time, researchers through history who discovered new bacteria grouped many diverse species under the “umbrella” of the genus Lactobacillus. Since the naming of the first Lactobacillus species, Lactobacillus delbrueckii, in 1901, microbial taxonomists assigned over 250 species to this genus.

These species were a diverse group, and when DNA analysis tools became more sophisticated, many were found to be only loosely related. A consensus grew among scientific experts that, given the genetic makeup of these bacteria, the current Lactobacillus genus was too diverse and did not conform to nomenclature conventions. Moreover, it was important to split the genus into functionally relevant groups that shared certain physiological, metabolic properties and lifestyles in order to facilitate functional and ecological studies on bacteria from this genus.

To tackle this problem, 15 scientists (see below) from 12 different institutions and 7 different countries came together, applying whole genome analysis to analyze each Lactobacillus species. Their proposal, which was accepted for publication in the official journal of record for bacterial names, is that the species once contained within the Lactobacillus genus should now spread over 25 genera, including 23 novel genera (see paper link here).

Based on this polyphasic approach, the authors reclassified the genus Lactobacillus into 25 genera including the emended genus Lactobacillus, which includes host-adapted organisms that have been referred to as the L. delbrueckii group; Paralactobacillus; as well as 23 novel genera: Acetilactobacillus, Agrilactobacillus, Amylolactobacillus, Apilactobacillus, Bombilactobacillus, Companilactobacillus, Dellaglioa, Fructilactobacillus, Furfurilactobacillus, Holzapfelia, Lacticaseibacillus, Lactiplantibacillus, Lapidilactobacillus, Latilactobacillus, Lentilactobacillus, Levilactobacillus, Ligilactobacillus, Limosilactobacillus, Liquorilactobacillus, Loigolactobacilus, Paucilactobacillus, Schleiferilactobacillus, and Secundilactobacillus.

While genus names have changed in some cases, the parts of the names that indicate species were not changed. See the table below for some examples of how names of important probiotic lactobacilli have changed. Note that all new genera proposed for this group begin with the letter “L”. Thus, the ‘L.’ genus abbreviation may still be used.

Because of the importance of this genus and the implications of the name change for both science and industry, the researchers involved in this project have developed a web-based tool that makes it very easy to determine the new names of all Lactobacillus species.

Scientifically, one exciting outcome of these new taxonomic groupings is that species that are more closely related, and therefore are more likely to share physiological traits, are grouped into the same genus. This may facilitate our understanding of common mechanisms that may mediate health benefits, as described in an ISAPP consensus paper and a publication entitled “Shared mechanisms among probiotic taxa: implications for general probiotic claims”.

To date, bacteria in the group Bifidobacterium have not changed, but nomenclature changes are expected soon for this genus, too.

The Lactobacillus taxonomy changes are summarized in this ISAPP infographic for scientists and in this ISAPP infographic for consumers.

Names of important Lactobacillus probiotic species

The following chart lists the new names for some prominent Lactobacillus probiotic species. (Note: All new genera proposed for this group begin with the letter “L”, so abbreviated genus/species – such as L. rhamnosus – remain unchanged.)

 

Current name New name
Lactobacillus casei Lacticaseibacillus casei
Lactobacillus paracasei Lacticaseibacillus paracasei
Lactobacillus rhamnosus Lacticaseibacillus rhamnosus
Lactobacillus plantarum Lactiplantibacillus plantarum
Lactobacillus brevis Levilactobacillus brevis
Lactobacillus salivarius Ligilactobacillus salivarius
Lactobacillus fermentum Limosilactobacillus fermentum
Lactobacillus reuteri Limosilactobacillus reuteri
Lactobacillus acidophilus Unchanged
Lactobacillus delbrueckii subsp. bulgaricus

(aka Lactobacillus bulgaricus)

Unchanged
Lactobacillus crispatus Unchanged
Lactobacillus gasseri Unchanged
Lactobacillus johnsonii Unchanged
Lactobacillus helveticus Unchanged

Authors

  • Jinshui Zheng, Huazhong Agricultural University, State Key Laboratory of Agricultural Microbiology, Hubei Key Laboratory of Agricultural Bioinformatics, Wuhan, Hubei, P.R. China.
  • Stijn Wittouck, Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium
  • Elisa Salvetti, Dept. of Biotechnology, University of Verona, Verona, Italy
  • Charles M.A.P. Franz, Max Rubner-Institut, Department of Microbiology and Biotechnology, Kiel, Germany
  • Hugh M.B. Harris, School of Microbiology & APC Microbiome Ireland, University College Cork, Co. Cork, Ireland
  • Paola Mattarelli, University of Bologna, Dept. of Agricultural and Food Sciences, Bologna, Italy
  • Paul W. O’Toole, School of Microbiology & APC Microbiome Ireland, University College Cork, Co. Cork, Ireland
  • Bruno Pot, Research Group of Industrial Microbiology and Food Biotechnology (IMDO), Vrije Universiteit Brussel, Brussels, Belgium
  • Peter Vandamme, Laboratory of Microbiology, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium
  • Jens Walter, Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, Canada; Department of Biological Sciences, University of Alberta, Edmonton, Canada
  • Koichi Watanabe, National Taiwan University, Dept. of Animal Science and Technology, Taipei, Taiwan R.O.C.; Food Industry Research and Development Institute, Bioresource Collection and Research Center, Hsinchu, Taiwan R.O.C.
  • Sander Wuyts, Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium
  • Giovanna E. Felis, Dept. of Biotechnology, University of Verona, Verona, Italy
  • Michael G. Gänzle, Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, Canada; Hubei University of Technology, College of Bioengineering and Food Science, Wuhan, Hubei, P.R. China.
  • Sarah Lebeer, Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium.

See ISAPP’s press release on the Lactobacillus name changes here.

ISAPP Students and Fellows Association announce blog posting: A new way to share our work and perspectives

By Anna-Ursula Happel, president ISAPP-SFA and postdoctoral fellow at the Faculty of Health Sciences at the University of Cape Town, South Africa

Our professors keep telling us to write, write, write. Reports, papers, reviews, presentations. You can’t blame them as that’s what most of them had to do, and in a competitive environment academic output is critical. But while professors urge students to produce academic outputs, there’s a whole world of research ‘impact’ in a digital world that is beginning to matter for career advancement. To further our reach along this axis, we as the ISAPP-Students and Fellows Association (SFA) are launching a blog platform, which will be regularly updated with perspectives from our members and ideas on recent developments in the field of probiotics and prebiotics.

Our very first blog post centered on an innovative project I never thought I would hear about. Through our SFA meeting, I had heard about the Reid lab from Western University in Canada trying to find a way to prevent the decline of honey bee populations. It was a shock, since their focus for years has been women’s health. My first question to one of Dr. Reid’s students, Brendan Daisley, was: How did this come about? It turns out, the interest in how environmental toxins affect humans led to wondering how it helped really important pollinators. Not such a tangential switch as I’d thought. But what’s this got to do with the field of probiotics and my career?

Well, it shows that probiotics, as the definition states, can be applied to many hosts. It also shows that the microbiome plays a role in the health of insects as well as humans. And many of the study tools are the same – microbiota analysis, bioinformatics, immune responses, etc., yet some are totally different – using Drosophila models, counting larvae, measuring honey volumes. Read more about it here. The lesson for me: think laterally, look at how you can apply your knowledge, think of ecosystem health, and learn lots of basic skills.

Then, I thought to myself, how can research provide me with opportunities for developing leadership, initiatives and skills that are valuable for my careers. How can I gain visibility as an early-career researcher, grow my networks, improve my writing and scientific communication skills and find a platform to highlight projects that matter to me? The new blog will be helpful for all of this.

As members of the SFA, we’re very fortunate to have our voices heard; to organize our own annual meeting (well, except for 2020 when the world shut down); to be exposed to amazing scientists and ground breaking ideas – and to communicate our work, ideas and perspectives to a broad audience through our new blog. Beyond formal networking at annual meetings, the SFA blog now offers a way to stay actively connected throughout the entire year on a more informal platform with our peers, may strengthen ties within the community and even lead to collaborations and career opportunities.

See here for the ISAPP-SFA blog — bookmark it or watch for new posts on social media!

Twitter: @ISAPPSFA

 

Probiotics in fridge

The FDA’s view on the term probiotics, part 2: Further down the rabbit hole

By James Heimbach, Ph.D., F.A.C.N., JHEIMBACH LLC, Port Royal, VA

A number of weeks ago I wrote on the ISAPP blog about US Food and Drug Administration (FDA) declining to file Generally Regarded As Safe (GRAS) notices that described the subject microorganism as a “probiotic” or “probiotic bacterium” (see The FDA’s view on the term “probiotics”). Now the FDA’s response to such GRAS notices has developed additional ramifications. Let me put them into two categories: Class 1 misdemeanors that will cause FDA to reject the notice, and Class 2 misdemeanors that will probably not prevent filing, but will cause FDA to raise questions. I should note that these thoughts are based on both my own direct experiences and my repeated telephone conference calls with FDA.

Class 1 Misdemeanors

  1. Using the term probiotic in any way in describing or characterizing the subject microorganism or its past, present, or intended use.
  2. Extended discussion of benefits derived from ingestion of the microorganism in animal or human research.
  3. Any mention, however brief, of the potential for the microorganism to be used in dietary supplements.

Class 2 Misdemeanors

  1. Including brief mentions of the microorganism serving as a probiotic. E.g., if you cite a study of the microorganism that you might previously have reported as “a study of the probiotic benefits” of the microorganism, change it to simply “a study of the benefits” of the microorganism. This same caution is advised when reporting opinions from the European Food Safety Authority (EFSA) or other authoritative bodies.
  2. Using the word “dose” in describing intended use. Also see #4 below.
  3. Virtually any use of the term “dietary supplement,” including in reporting past, current, or intended uses of the strain or the species in Europe or elsewhere, by anyone.
  4. Even relatively brief mentions of benefits. The recommended way of handling reporting of human studies of the species or strain is to avoid any narrative at all. Simply summarize the studies in tabular form, listing the citation, study design (RCT, open-label, etc.) and objective, study population (number, sex, age, characterization such as IBS patients, malnourished children, preterm infants), test article (microorganism binomial and strain), dose (but call it “administration level”—“dose” can be seen as indicating a drug or dietary supplement), duration, and safety-related results. Include methods used to ensure that any adverse events or severe adverse events would have been reported—medical examinations, self-report questionnaires, parental questionnaires, biochemical measures, etc.—and at what time points during or after the in-life portion of the research. Avoid ANY discussion of improvements seen in the test group.

Good luck!

The FDA’s view on the term probiotics, part 1

By James Heimbach, Ph.D., F.A.C.N., JHEIMBACH LLC, Port Royal, VA

James Heimbach, food and nutrition regulatory consultant

Over the past 20 years as a food and nutrition regulatory consultant, I have filed about 40 GRAS notices with the United States Food and Drug Administration (FDA), including 15 strains of probiotic bacteria and 5 prebiotics. This fall I submitted notices dealing with 4 strains of bacteria and on January 16 received a telephone call from FDA that surprised me and initially infuriated me, but which I have come to understand.

The essence of the call was that FDA was declining to file my probiotic notices because the notices had identified the subject bacteria as “probiotics” or “probiotic bacteria.” FDA suggested that I resubmit without calling the subject microorganisms “probiotics.”

 

 

As I said, I was surprised and frustrated, and I still would prefer that when FDA makes a policy swerve they would do it in a way that does not make extra work for me and delay my clients’ ability to get to market in a timely manner.

What I have had to do here is remove my advocate’s hat and put on my regulator’s hat. (I worked for FDA for a decade . . . long ago [1978 to 1988], but I still remember how to think like a regulator.) And here is the issue. Recall that GRAS is concerned with safety, not efficacy (generally recognized as safe, or GRAS), and the information provided in a GRAS notice is focused on safety (although benefits may be more-or-less incidentally covered). The reviewers at FDA are charged with assessing whether the notice provides an adequate basis to conclude that there is a reasonable certainty that no harm will result from the intended use. They are not charged, and they are not equipped, to evaluate what benefits ingestion of the substance or microorganism might provide. So they are not in a position to say whether the subject microorganism will “confer a health benefit on the host,” which is to say, they are not in a position to say whether or not it may be regarded as a probiotic. Remember, probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (Hill et al. 2014).

Given that the FDA reviewers cannot say whether the notified microorganism is rightly called a probiotic, they are reluctant to sign off that they have no questions about a notice that calls it one. Regulatory agencies have to be careful; things sometimes come back to haunt them. Those who have been following FDA’s GRAS-notice response letters for a couple of decades will be aware that the agency is putting more and more disclaimers into the letters—about standards of identity, about potential labeling issues, about benefits shown in clinical trials, and about Section 201(II) of the FD&C Act.

One concern that FDA likely has is that if some issue comes up in the future regarding a claim made for benefits from use of a product containing the subject bacterium, someone may make the argument that FDA had accepted that the strain is indeed a probiotic and so it presumably confers probiotic benefits. In the case of probiotics, there are also some internal FDA politics. As ISAPP meeting attendees may already be aware, FDA’s Center for Biologics Evaluation and Research (CBER) would like to claim jurisdiction over all administration of live microorganisms, and the Center for Food Safety and Applied Nutrition (CFSAN) does not seem willing to have a confrontation.

I suspect that a similar situation obtains with the term “prebiotic.” Although I have filed a number of GRAS notices for prebiotics, they haven’t been called that; they have been called fructooligosaccharides, or tamarind seed polysaccharide, or polydextrose, or 2’-O-fucosyllactose. I don’t know how FDA would respond if a GRAS determination were filed with the substance labeled as a prebiotic.

So, I’ve decided that my sympathies lie with FDA. Until and unless a microorganism has been confirmed by competent authority to have probiotic properties when used as intended in a GRAS notice, FDA is probably correct in rejecting its right to be labeled a probiotic. If it’s any consolation, this new position by the FDA has its origin in their acknowledgment of the official scientific definition of the word “probiotic”.

When Mary Ellen Sanders (ISAPP’s Executive Science Officer) reviewed my first draft of this note, she asked what I had in mind by “competent authority,” to which I don’t have a good answer at the present time except to insist that it is not FDA’s Division of GRAS Notice Review. Thirty years ago, when I was at FDA, I was in the Office of Food Science and Nutrition, and that office was charged with making determinations of that type (although I don’t recall anything about probiotics coming before us). But FDA no longer has such an office. Until it does, or until it agrees on another source of authority on designation of microorganisms as non-CBER-domain probiotics, I suspect that CFSAN will continue to be very cautious in this area.

Read part 2 of this blog series here.

ISAPP discussion group leads to new review paper providing a global perspective on the science of fermented foods and beverages

By Kristina Campbell, MSc, Science & Medical Writer

Despite the huge variety of fermented foods that have originated in countries all over the world, there are relatively few published studies describing the microbiological similarities and differences between these very diverse foods and beverages. But in recent years, thanks to the availability of high throughput sequencing and other molecular technologies combined with new computational tools, analyses of the microbes that transform fresh substrates into fermented foods are becoming more frequent.

A group of researchers from North America, Europe, and Asia gathered at the International Scientific Association for Probiotics and Prebiotics (ISAPP) 2018 conference in Singapore to discuss the science of fermented foods. Their goal was to provide a global perspective on fermented foods to account for the many  cultural, technological, and microbiological differences between east and west. This expert panel discussion culminated in a new review paper, published in Comprehensive Reviews in Food Science and Food Safety, entitled Fermented foods in a global age: East meets West.

Prof. Robert Hutkins, the paper’s lead author, says the diversity of panelists in the discussion group was an important aspect of this work. “Although we were all connected by our shared interests in fermented foods, each panelist brought a particular expertise along with different cultural backgrounds to our discussions,” he says. “Thus, one of the important outcomes, as noted in the published review paper, was how greatly historical and cultural factors, apart from microbiology, influence the types of fermented foods and beverages consumed around the world.”

The review captures the current state of knowledge on the variety of microbes that create fermented foods: whether these are starter cultures or microbes already present in the surrounding environment (i.e. the ‘authochthonous’ or ‘indigenous’ microbiota). The paper identifies general region-specific differences in the preparation of fermented foods, and the contrast between traditional and modern production of fermented foods—including the trade-offs between local and larger-scale manufacturing.

The authors of the article also took on the painstaking work of cataloging dozens of fermented foods from all over the world, including fermented milk products, fermented cereal foods, fermented vegetable products, fermented legume foods, fermented root crop foods, fermented meat foods, fermented fish products, and alcoholic beverages.

The expert panel discussions held every year at the ISAPP annual meeting provide a much-anticipated opportunity for globally leading scientists to come together to discuss issues relevant to scientific innovation and the direction of the field. This paper is an example of a concrete outcome of one of these discussion groups.

For more on fermented foods, see this ISAPP infographic or this educational video.

ISAPP helps inform UK Parliament

By Prof. Glenn Gibson, University of Reading, UK

An All Party Parliamentary Group (APPG) was inaugurated in February 2019 in the UK. Its purpose is: “to highlight the role of the gut microbiome in physical and mental health and its capacity to prevent many disorders and improve or slow others; to inform debate about how this will save money for the Treasury and NHS; and to enable communications between interested parties and relevant parliamentarians.” At this stage, over 80 MPs and Peers are currently involved, with Julie Elliott MP as chair.

iStock photo. Credit: Vladislav Zolotovby. Houses of Parliament and Big Ben at sunset, London, UK.

The APPG meetings (6 per year) provide opportunities to share information based on sound science and reality, not hype, so that parliamentarians can take appropriate action when opportunities arise. Specific experts are invited to give the evidence, and the topics discussed so far include:

  • overview of gut microbiology and health
  • potential savings for the NHS/treasury if evidenced probiotics and prebiotics were to be applied to specific clinical states
  • management of gut health in elite athletes
  • benefits of pro- and prebiotics for the wider community

Alan Barnard presents about the APPG at the 2019 ISAPP annual meeting.

Scientific advisors for the APPG are ISAPP board of directors member Dr. Glenn Gibson, Dr. Kirsty Hunter (Nottingham Trent University), and Dr. Gemma Walton (University of Reading).  The secretariat is Alan Barnard. Kirsty and Alan attended the ISAPP 2019 annual meeting in Antwerp to give an overview of the aspirations and format of the APPG. The advisors use ISAPP science to drive the communications, including the organization’s review articles, consensus statements, infographics, videos, and selected working group summaries from the annual meetings. ISAPP anticipates further involvement with the APPG, including a future meeting featuring Gregor Reid’s outstanding probiotic research in the developing world.

 

Harmonized Probiotic Guidelines to be discussed at Codex Alimentarius meeting November 24 – 29

By Mary Ellen Sanders PhD, Executive Science Officer, ISAPP

In 2017, the International Probiotics Association (IPA) proposed that Codex Alimentarius consider the topic of global harmonization of probiotics, and Argentina offered to propose an approach. The final proposal developed by Argentina is here.

This set into motion activities among many stakeholders that led to a final proposal, to be discussed at the Joint FAO/WHO Food Standards Programme, Codex Committee on Nutrition and Foods For Special Dietary Uses, Forty-first Session, Dusseldorf, Germany, being held 24 – 29 November 2019. The agenda for this meeting includes “Harmonized Probiotic Guidelines for Use in Foods and Dietary Supplements”, agenda item #11.

ISAPP has long championed the need for the term ‘probiotic’ to be used on product labels only when the scientifically recognized definition is met. In June 2018, ISAPP convened a large group of industry and academic scientists, chaired by Profs. Seppo Salminen (Finland), Yuan Kun Lee (Singapore), and Gabriel Vinderola (Argentina), to discuss global harmonization. Prof. Vinderola later served as a member of the Argentinian committee that developed the proposal now under consideration. From this discussion group, a white paper “ISAPP position statement on minimum criteria for harmonizing global regulatory approaches for probiotics in foods and supplements” was prepared, describing the minimum criteria for use of the term ‘probiotic’. These outputs frame an overall position of ISAPP on this issue: any global regulations should impose only the minimum criteria necessary to ensure truthful product labeling.

Issues such as requiring specific safety tests, stipulating specific in vitro or animal studies, or expecting manufacturers to automatically re-conduct clinical trials when changing delivery matrices, will serve to inhibit innovation and impose expensive requirements that may not be necessary.

Although probiotics can be considered unique in that they are live microorganisms, their use as dietary ingredients is not substantively different from other ingredients. Every ingredient needs specific analytical techniques and has specific requirements for identity, purity, and stability. So if truth in labeling can be assured regarding proper commercial use of the term ‘probiotic’, there may not be a need for carved-out global regulations on probiotics.

The position of the United States on this agenda item is: “The United States is still reviewing the discussion paper and has not formed a position at this time. We note however that in our view this work is lower in priority than proposed work on nutrient profiles.”

Reflections on a career in probiotic science, from ISAPP founding board member Prof. Gregor Reid

Past President and founding board member Prof. Gregor Reid is stepping down from the ISAPP Board in Banff in June 2020, as he retires from Western University and his Endowed Chair position at Lawson Health Research Institute the following month. In this blog post, he shares thoughts on his career and the opportunities for his replacement and for others to continue probiotic research. See here for information on the position of Research Chair in Human Microbiome and Probiotics at the Lawson Health Research Institute.

By Gregor Reid BSc (Hons), PhD, MBA, ARM CCM, Dr HS, FCAHS, FRSC

A mere blue dot. A pinhead, if that. But it’s us, all we have been and all we will be – for a while at least. The planet Earth.

Its magnificence is there for all to see.

Creative Commons Earth Illustration, Pixabay

Creative Commons Earth Illustration, by Pixabay

I’ve been fortunate to have visited over 60 of the countries on this majestic globe. One of the perks of being a scientist. And for those who know me well, I’ve taken my camera and my music with me on the journey. In this blog post, I’ll share some pieces of both and how they form part of who we are and what we study.

Across the vast surface of our planet, and within it, there are countless microbes. As life emerges from the surface, we shouldn’t be surprised that microbes climb on board. Whether plants, honey bees, fish, birds, lions, humans, microbes accompany each.

Photo by Andrew Pitek. Used with permission.

Just being human is a guest house1.

Understandably, since some of these microbes can be deadly to humans, our ancestors had to find ways to stop them. Whether plague, diphtheria, smallpox, influenza, wound infections, or other fatal diseases. And so, the marvels of vaccination and antibiotics were born.

Arguably, these miraculous interventions also brought complacency as a societal side-effect, despite the warnings of people like Alexander Fleming. The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin2.

We all but ignored the collateral damage, pacified by label warnings of diarrhea and nausea until Clostridium difficile woke us from our slumber. When the antibiotics stopped working, we went out into left field and started using human poop! Too ridiculous to work, until it worked. Really well.

We’re running through the dark, and that’s how it starts. Don’t know what you’re doing to me. And it might be getting better3.

Prior to that radical step, an awakening had occurred through people like Metchnikoff but more recently Savage, Tannock, McKay, Costerton, Bruce, and others who led us to the microbes that have been helping us all along. In the case of Andrew Bruce, he wondered if replenishment of lactobacilli into the urogenital tract of women might help prevent recurrence of infection. But in the late seventies and early eighties, the collective ‘we’ wasn’t ready to listen.

You came like a comet, blazing your trail. Too high, too far, too soon, you saw the whole of the moon4.

In 2001 in the city of Cordoba, Argentina, a group of experts were assembled and asked to come up with a definition for probiotics5. This helped set a path that we remain on today.

But a definition is nothing without application and acceptance and stewardship. It requires passage to voices across the world. That is why the International Scientific Association for Probiotics and Prebiotics (ISAPP) has been a mountain overseeing the field. Led so wonderfully by Mary Ellen Sanders, Glenn Gibson and other outstanding scientists, it is symbolic of the climb many have had to make.

If you understand or if you don’t. If you believe, or if you doubt. There’s a universal justice, and the eyes of truth are always watching you6.

There’s always gonna be another mountain. I’m always gonna wanna make it move. Always gonna be an uphill battle. Sometimes I’m gonna have to lose. Ain’t about how fast I get there, ain’t about what’s waiting on the other side. It’s the climb7.

It has certainly been a climb. For each of us. Cynicism too often outweighing optimism. Hype outweighing truth. Profit ahead of science. Ignorance over understanding. But together, we have reiterated the message, the importance of studies and data. Not in experimental mice or test tubes, but in the ultimate host where benefits are sought.

The road has taught me to fight our corner, but also that there is a magnificence and mystery in this planet we share. From the birth of a baby to the honey bee that pollinates our crops, to the salmon that crosses from salt to fresh water and back. All from the Mother we share8.

I’ve been fortunate that my career has allowed me to pursue my dream, although it’s never quite as it seems9. One song sums it up for me: While I’m alive I’ll make tiny changes to earth10.

I hope that I have made some tiny changes, especially in the poorest regions of Africa where the probiotic fermented foods of Western Heads East and Yoba-for-life are impacting lives of the young and old. Such inspiring people!

I think if each person is able to make tiny changes, we can leave this life better than whence we came.

As retirement looms, it’s funny how the same question is asked repeatedly. “So, what will you do now?” My answer is I’m moving to America. It’s an empty threat11. Actually, I think back to second year of my honours’ degree at Glasgow University and second year of my PhD at Massey University when my answer was “I don’t know for sure, but I’ll do my best.” I think we need to follow the voice inside us and hope that tomorrow brings wellness and satisfaction.

I won’t fill my walls with framed degrees or awards. Those are for photo albums of a blessed past. They were made possible because of hard work, an incredible family, and a set of friends and talented colleagues too numerous to name.

I’m proud of my publications and students, and hope they inspire others. But I only have two hands12, and we need the Big Ideas for you and me13. So, the laboratory, supplies, offices, and amazing staff and students at the St. Joseph’s Hospital site in London, Ontario await a new direction and someone to carry the fire14. For whoever is my successor, I will wish that tomorrow brings another day, another ray of hope15 and that he or she remembers you only get what you give16, and you only get one shot, do not miss your chance17.

Scientific endeavour, an open mind, supportive colleagues, and taking chances all make for an exciting career. I followed a path barely walked. It ostracized me from many in mainstream microbiology. When grant panel reviewers don’t believe your work has value or is needed, life gets challenging. So, you follow your heart, you lean on those who agree with you, and publish on peripheral topics to stay noticed. Then you smile when your critics actually start studying beneficial microbes and probiotics, and understand what you’ve been saying all along.

Probiotics are more than science. They encompass a philosophy, an anthropological perspective, a bridge between past and future. They are a mountain range of possibilities. As researchers we are still people. We should never shut out the disciplines and sounds and voices that surround us. We need to awaken them like adding medium to a dried Lactobacillus and watching it grow.

The possibilities are just as endless as when I started. But they need younger hands with the latest and future technical skill-sets to pursue the big ideas and to be a steward in defending probiotic science and excellence. These are indeed exciting times.

In closing, I hope you enjoy the music selection — and the irony of some of the album names.

As for me heading into the sunset of this journey: Let the music play. I just wanna dance the night away18.

References (unlike any you’ve seen before)

  1. Coldplay. 2017. Kaleidoscope, from A Head Full of Dreams.
  2. Alexander Fleming. 1945. In, The New York Times.
  3. British Sea Power. 2017. What You’re Doing, from Let the Dancers Inherit the Party.
  4. The Waterboys. 1985. The Whole Of The Moon, from This is the Sea.
  5. Food and Agriculture Organization of the United Nations and World Health Organization. 2001. Probiotics in Food. http://www.fao.org/3/a-a0512e.pdf
  6. Enigma. 1993. The Cross Of Changes from album of the same name.
  7. Miley Cyrus. 2009. The Climb, from Hannah Montana: The Movie.
  8. Chvrches. 2013. The Mother We Share, from The Bones of What You Believe.
  9. The Cranberries. 1992. Dreams, from Everybody Else is Doing It.
  10. Frightened Rabbit. 2008. Head Rolls Off, from Midnight Organ Fight.
  11. Kathleen Edwards. 2012. Empty Threat, from Voyageur.
  12. Avicii. 2013. Wake Me Up, from True.
  13. The Boxer Rebellion. 2016. Big Ideas, from Ocean by Ocean.
  14. Editors. 2010. No Sound But The Wind, from the Twilight Saga: New Moon.
  15. Bill Nelson. 1983. Another Day, Another Ray of Hope, from Chimera.
  16. New Radicals. 1998. You Get What You Give, from Maybe You’ve Been Brainwashed Too.
  17. Eminem. 2002. Lose Yourself, from the movie 8 Mile.
  18. Barry White. 1975. Let The Music Play, from the album of the same name.

See here for information on the position of Director of Human Microbiome and Probiotics at the Lawson Health Research Institute.

Researchers submit recommendations for revised Lactobacillus taxonomy

By Mary Ellen Sanders PhD, Executive Science Officer, ISAPP

A team of researchers has submitted their recommendations for new classification for the heterogeneous group of species currently considered to belong to the genus Lactobacillus. The paper is under review by the International Journal of Systematic and Evolutionary Microbiology, the premier journal for bacterial taxonomy.

Three research teams that were independently working on comparative genomics and taxonomic inconsistencies among lactobacilli (see here, here, here, here, here, and here) came together to openly collaborate on this publication. These teams included scientists from Italy, Canada, Belgium, Germany, China, Ireland, and Japan.

Several species important from a commercial perspective will be impacted, including Lactobacillus casei, Lactobacillus plantarum, Lactobacillus sakei, Lactobacillus salivarius, Lactobacillus reuteri and Lactobacillus brevis. New genus names are expected for these. Lactobacillus delbrueckii, Lactobacillus acidophilus, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus helveticus and Pediococcus are not expected to undergo name changes. Since L. delbrueckii (which includes the subspecies L. delbrueckii subspecies bulgaricus, the yogurt starter culture) was the first Lactobacillus named, convention in naming bacterial genera requires that species from this taxonomic clade will keep the Lactobacillus name.

Driving this effort is the pressing need to apply modern phylogenetic methods to establishing relationships among the many species of Lactobacillus (see previous post). The genus Lactobacillus currently comprises more than 240 species, and has been growing rapidly for decades. In 1980, 36 Lactobacillus species were recognized. By 2012, there were 152. Scientists recognized the need to reorganize the phylogenetic assignments of this genus; they are proposing splitting the Lactobacillus genus into more than 20 genera.

Once the paper is published, the task of disseminating the message about new genus names for commercially important species will begin.

See here for a detailed article on this topic.

new_website

ISAPP launches new website, furthering its mission of educating stakeholders on probiotic and prebiotic science

The ISAPP Board of Directors is pleased to announce the launch of the organization’s new website, which has now gone live at ISAPPscience.org. The website has been redesigned for easier navigation by different stakeholder groups—scientists, consumers, clinicians, and students—enabling ISAPP to continue with its mission of providing accurate, science-based information to its readers about probiotics, prebiotics and fermented foods.

ISAPP Executive Science Officer Dr. Mary Ellen Sanders says, “The scientists comprising the ISAPP Board of Directors realize that consumers and clinicians often struggle to find science-based information on probiotics and prebiotics. ISAPP is working to fill this gap, and we have streamlined our website to help individuals from each of these groups easily find the information they’re looking for.”

At the ISAPP annual meeting held earlier this year, advancing probiotic and prebiotic evidence to a variety of audiences was the topic of a special ‘springboard discussion’ session.

“Probiotic and prebiotic science has made significant progress in the past few decades,” says Sanders, “but this progress has not always been communicated effectively or correctly to those outside the scientific community.” Sanders continues, “Some studies describe an expanding array of health benefits but other studies show the limits of these interventions. Our goal is to counter the abundance of misinformation and be the go-to source of accurate materials about probiotics and prebiotics.”

ISAPP is building its capacity to produce more science-focused educational materials tailored to different audiences. Infographics, some of which are translated into 10 different languages, short videos and targeted blogs are featured on the new website. In coming weeks, ISAPP will make additional resources available on the website, including frequently asked questions about probiotics and prebiotics, and a downloadable white paper for clinicians. Signing up for the ISAPP newsletter is the best way to stay up to date on educational materials being added to the website.

ISAPP’s 2019 annual meeting in Antwerp, Belgium: Directions in probiotic & prebiotic innovation

Kristina Campbell, Microbiome science writer, Victoria, British Columbia

We live in a time when a simple Google search for ‘probiotics’ produces over 56.8 million hits; a time when almost everyone has heard of probiotics through one channel or another, and when an ever-increasing variety of probiotic and prebiotic products is available in different regions of the world.

The next five to ten years will be telling: will probiotics and prebiotics join the ranks of other trendy health products that experienced a wave of popularity before something else took their place? Or will they be recognized as important contributors to health through the lifespan, and establish a permanent position in the clinical armamentarium?

According to the global group of 175 academic and industry scientists who met for the ISAPP annual meeting in Antwerp (Belgium) May 14-16, 2019, one thing above all is necessary for the world to recognize the significance of probiotics and prebiotics for health: scientific innovation. Not only are technological capabilities advancing quickly, but also, new products are being evaluated by better-educated consumers who demand more transparency about the health benefits of their probiotics and prebiotics.

Participants in the ISAPP conference came together to talk about some of the leading innovations in the world of probiotics and prebiotics. Here are three of the broad themes that emerged:

Better health through the gut-brain axis

Gut-brain axis research is rapidly growing, with many investigators in search of probiotic and prebiotic substances capable of modulating brain function in meaningful ways. Phil Burnett of Oxford (UK) presented on “Prebiotics, brain function and stress: To what extent will prebiotics replace or complement drug therapy for mental health?”. Burnett approached the challenge by administering prebiotics to healthy adults and giving them a battery of psychological tests; in one experiment he found people who consumed a prebiotic (versus placebo) showed benefits that included reduced salivary cortisol and positively altered emotional bias. For those with diagnosed brain disorders, Burnett concludes from the available data that prebiotics have potential anxiolytic and pro-cognitive effects in these populations, and that prebiotics may eventually be used to complement the established treatments for some mental disorders.

Short-chain fatty acids (SCFAs) are of interest as potential modulators of brain function, but so far very little research has been carried out in this area. Kristin Verbeke of Leuven (Belgium) gave a talk entitled “Short-chain fatty acids as mediators of human health”, which covered the extent to which interventions with fermentable carbohydrates can alter systemic SCFA concentrations (rather than gut SCFA concentrations)—since the former are more relevant to effects on the brain.

Also, a students and fellows feature talk by Caitlin Cowan of Cork (Ireland) explored a role for the microbiota in psychological effects of early stress. She spoke on the topic “A probiotic formulation reverses the effects of maternal separation on neural circuits underpinning fear expression and extinction in infant rats”.

A clear definition of synbiotics

Immediately before the main ISAPP meeting, a group of experts met to propose a consensus definition of ‘synbiotic’, with the objective of clarifying for stakeholders a scientifically valid approach for the use of the increasingly-popular term. A key point of discussion was whether the probiotic and prebiotic substances that make up a synbiotic are complementary or synergistic. And if the two substances have already been tested separately, must they be tested in combination to give evidence of their health effect? The group’s conclusions, which will undoubtedly steer the direction of future R&D programs, will be published in a forthcoming article in Nature Reviews Gastroenterology & Hepatology.

Probiotics and prebiotics for pediatric populations

Probiotics and prebiotics have been studied for their health benefits in pediatric populations for many years, but in this area scientists appear to have a renewed interest in exploring new solutions. Maria Carmen Collado of Valencia (Spain) covered “Probiotic use at conception and during gestation”, explaining some of the most promising directions for improving infant health through maternal consumption of probiotics.

In recent years, technical advancements have made possible the large-scale production of some human milk oligosaccharides (HMOs); it is now an option to administer them to infants. Evelyn Jantscher-Krenn of Graz (Austria) presented a novel perspective on HMOs, with “HMOs in pregnancy: Roles for maternal and infant health”, giving a broad overview of the many ways in which HMOs might signal health status and how they might be fine-tuned throughout a woman’s pregnancy.

A discussion group on “prebiotic applications in children”, chaired by Dr. Michael Cabana of San Francisco (USA) and Gigi Veereman of Brussels (Belgium), discussed evidence-based uses of prebiotics in children in three areas: (1) prevention of chronic disease; (2) treatment of disease; and (3) growth and development. While the latter category has the best support at present (specifically for bone development, calcium absorption, and stool softening), the other two areas may be ripe for more research and innovation. The chairs are preparing a review that covers the outcomes of this discussion group.

Next year in Banff

ISAPP’s next annual meeting is open to scientists from its member companies and will be held on June 2-4, 2020 in Banff, Canada.

 

Photo by http://benvandenbroecke.be/ Copyright, ISAPP 2019.

Thank You to ISAPP’s 2019 Industry Advisory Committee Members

by Dr. Mary Ellen Sanders

This year, a record 50 companies that are dedicated to a science-based approach to the probiotic and prebiotic industries joined ISAPP. As members of the Industry Advisory Committee (IAC), these companies provide critical insights to ISAPP’s all-academic board of directors as they leverage ISAPP to address challenges facing these and related industries.

ISAPP will welcome representatives from each IAC company at the ISAPP Annual Meeting – taking place next week May 14th-16th in Antwerp, Belgium.

Industry dues provide support for ISAPP activities, which would not be possibly without funding by our IAC members. Summaries of ISAPP activities are found here.

Thank you IAC!

ISAPP Tests the Water with a New Session Format at Annual Meeting: The Springboard

By Mary Ellen Sanders PhD, Executive Science Officer, ISAPP

Along with more traditional lectures, the distinctive five-minute rapid-fire late breaking news session and the small, topical discussion groups have been staples of the annual ISAPP meetings. This year in Antwerp, ISAPP is trying yet another innovative approach – a session we are calling “The Springboard.” The witty Prof. Glenn Gibson will chair, sure to make the session entertaining as well as inspiring.

The Springboard is a session designed to integrate audience and facilitators’ viewpoints in an interactive format. The topic:  What can scientists and industry do to spring probiotics and prebiotics into mainstream health management? Four facilitators, each focused on a different perspective (industry, politics, medical/clinical or science/research), will present their visions. The audience, which will be divided into 10 subgroups, is challenged with the task of generating innovative ways to achieve the visions.

ISAPP plans to write up the most interesting solutions for publication. Watch for the output from this new session after the 2019 ISAPP annual meeting – May 14-16.

The Art of Interpretation

By Prof. Gregor Reid, BSc Hons PhD MBA ARM CCM Dr HS, Lawson Research Institute, University of Western Ontario, Canada

It takes a certain degree of intelligence to become a scientist, and certainly hard work to be able to fund a lab and students. Yet, is it not bemusing when scientists cannot interpret simple things like definitions and the results of human studies?

I’ve written repeatedly, as have others, about the definition of probiotics (in case you forgot – “Live microorganisms that, (or which) when administered in adequate amounts, confer a health benefit on the host”),1,2 and yet people look at it and must think that ‘dead’ fits, as does ‘consume’, as does ‘colonize’. It beggar’s belief how such a simple definition can be so badly interpreted by intelligent people.

Time after time papers I review mis-write and/or misinterpret the definition. Conference after conference, I hear dieticians, pharmacists, physicians, scientists not only get the definition wrong, but say things like ‘the probiotics in kombucha’ when there are none, ‘we have lots of probiotics in our gut’ when you don’t unless you consumed them, ‘the lactobacilli need to colonize’ when this was never a prerequisite nor does it happen except in rare instances.

The interpretation gets more difficult when people use terms that are completely undefined like ‘psycho-biotics’ and ‘post-biotics’. Even ‘dead probiotics’ have been used in clinical trials – God help us when the authors can’t even define it. Why stop at killing probiotic strains? Why not just kill any bacterial strain? Even the gut-brain axis which is now mentioned everywhere in the literature is undefined and unproven. The vagus nerve links to many body sites as does the nervous system, making it exceedingly difficult to prove that brain responses are only due to the gut microbes.

Everyone can site a manuscript that has been badly analyzed, interpreted or peer-reviewed, or whose findings are overblown. But let’s not excuse this as ‘it’s just science’ or ‘it’s just the way it is.’ No, it is not. When a paper uses a product that is stated to be ‘probiotic’, there is an onus on the authors to make sure the product meets the appropriate criteria. These have been stated over and over again and reiterated this March, 2019.3

If scientists and science writers are really that smart, then how do they keep getting this wrong? How do we let a poorly analyzed paper get published and allow authors to say that Bacteroides fragilis is a probiotic that can treat autism?4,5 And when this leads to companies claiming probiotics can treat autism, why do other scientists convey cynicism for the field instead of against their colleagues and specific companies making the false claims?

Where does opinion cross the line with ignorance or stupidity? Martin Luther King Jr. must have predicted life today when he said, “Nothing in all the world is more dangerous than sincere ignorance and conscientious stupidity.”

Is it envy or anger that drives the anti-probiotic sentiments? It seems to go far beyond a difference of opinion. When the BBC and JAMA fail to comment on two much better and larger studies on the effects of probiotics published6,7 at the same time as the ones in Cell8,9 that were promoted by press releases, what is driving opinion? The science or the press releases? Are the journalists and communications’ people interpreting study results vigorously? One cannot believe they are.

In an era where anyone can write anything at any time and pass it along to the world, what are we recipients to do? Just go with our instincts? Soon, we will not know the difference between fact and fake news. The avatars will be so real, we will act on falsehoods without knowing. When all news is fake, where does that leave us as people, never mind scientists?

Manuscripts are sent for peer-review but how many reviewers are experts in bioinformatics, molecular genetics, clinical medicine, biostatistics and what happens on the front line of products to consumers or patients? Like it or not, poor studies will get out there and it will be the media who will tell the story and interpret the findings or press releases.

One must hope that confirmatory science will continue and if it fails, the writers and readers will stop citing the original incorrect report. But how often does that happen? And what are we left with?

It takes effort to object or fight back, but if we don’t then the fake news will become the norm.

Try interpreting that if you will.

 

Literature Cited

  1.  FAO/WHO. 2001. Probiotics in food.  http://www.fao.org/food/food-safety-quality/a-z-index/probiotics/en/
  2. Hill C. et al. 2014. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotics. Nat. Reviews Gastroenterol. Hepatol. 11(8):506-14.
  3. Reid G. et al. 2019. Probiotics: reiterating what they are and what they are not. Front. Microbiol. 10: article 424.
  4. Hsiao et al. 2013. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 155(7):1451-63.
  5. Sharon G, et al. 2016. The central nervous system and the gut microbiome. Cell. 167(4):915-932.
  6. Korpela K. et al. 2018. Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants. Microbiome. 6(1):182.
  7. De Wolfe, T.J. et al. 2018. Oral probiotic combination of Lactobacillus and Bifidobacterium alters the gastrointestinal microbiota during antibiotic treatment for Clostridium difficile infection. PLoS One. 13(9):e0204253.
  8. Suez J. et al. (2018). Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell. 2018 Sep 6;174(6):1406-1423.e16.
  9. Zmora N. et al. 2018. Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell. Sep 6;174(6):1388-1405.e21.

University confers Distinguished University Professor status on ISAPP board of directors member Gregor Reid

ISAPP board of directors member Dr. Gregor Reid has received a Distinguished University Professorship (DUP) award from his institution, University of Western Ontario in Canada, in honour of his exceptional scholarly career achievements. Reid, a Professor of Microbiology & Immunology, and Surgery, was aptly described as ‘a Canadian and international pioneer’ in research related to probiotics and the microbiome. A special area of research focus is how these relate to women’s health.

The many letters after Reid’s name reflect his extensive qualifications: BSc Hons, PhD, MBA, ARM CCM, Dr HS, FCAHS, FRS; he also has over 500 scientific publications to his name. But more than that, the impact of Reid’s work is seen all over the world. He has researched novel probiotic therapies that are now being used in different countries and settings, and his innovations have resulted in numerous probiotic-related patents. Reid also makes a point of empowering those in need: in Uganda, Kenya, and Tanzania, for example, he participated in a project to establish probiotic yogurt kitchens that allowed local women to further build sustainable yogurt businesses.

Reid’s connection with ISAPP goes back a long way—he hosted the first ever ISAPP meeting in London, Canada in May of 2002, and served as ISAPP’s second president. Still a dedicated member of the ISAPP board of directors, he is respected for his innovative ideas to move ISAPP forward and his incredible efficiency. As his colleagues know, no one gets more done more quickly than Gregor!

Today he is known as a steward of the proper use of the term ‘probiotic,’ a fitting description since he chaired the FAO/WHO expert consensus that published the now globally-recognized definition of the word probiotic back in 2001.

The ISAPP colleagues of Dr. Gregor Reid extend a warm congratulations on his Distinguished University Professorship award; they applaud his remarkable scientific accomplishments, his energy, and his determination to help the field advance.

See here for the full news article about the award.