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60 Minutes’ 13 minutes on probiotics

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer 

On June 28, 60 Minutes aired a 13-minute segment about probiotics titled, “Do Probiotics Actually Do Anything?” Unfortunately the media segment did not provide listeners with a nuanced perspective.

‘Probiotics’ were treated as if they were one entity, ignoring the best approach to addressing the topic of what probiotics do: evaluate the evidence for specific strains, doses and endpoints, and then make a conclusion based on the totality of the evidence. They would have found that many experts agree that actionable evidence exists for certain probiotics to prevent antibiotic associated diarrhea (here, here), prevent upper respiratory tract infections (here), prevent morbidity and mortality associated with necrotizing enterocolitis (here,), treat colic (here), and treat acute pediatric gastroenteritis (here). (For an overall view of evidence, see here.)

Importantly, not all retail probiotics have evidence (at least evidence that is readily retrievable, see here and here). But that does not mean that none do.

The 60 Minutes segment also highlighted questions about probiotic safety. No intervention is without risk, and no one claims as much for probiotics. Prof. Dan Merenstein, MD, just one clinical investigator of probiotics, has collected over 20,000 pediatric clinical patient days’ worth of safety data over the past eight years of clinical investigation, with no indication of safety concerns. In fact, participants in the placebo group generally have more adverse events than in the probiotic groups. But importantly, the safety standard for probiotics was mischaracterized by 60 Minutes. According to Dr. James Heimbach, a food safety expert (not interviewed in the segment) who has conducted 41 GRAS determinations on probiotics, over 25 of them notified to the FDA, he objects to the statement that GRAS is a lower safety bar than a drug. He clarifies:

“The safety standard that applies to food additives and GRAS substances, “reasonable certainty of no harm,” is a far higher standard than that applying to drugs. Drugs are judged against a risk/benefit standard, which can potentially allow quite dangerous drugs on the market provided they offer a significant benefit. The safety standard for drugs also applies only to prescribed doses for specific individuals over prescribed durations. The food-additive/GRAS substance standard, on the other hand, requires safety at any biologically plausible level of intake, for any person (child, adult, elderly; pregnant; etc.), over a lifetime. And it is a risk-only standard—no potential benefit is allowed to override the “reasonable certainty of no harm” standard. Additionally, in the case of GRAS substances (which includes most probiotics), the evidence of safety must be published in the peer-reviewed scientific literature and be widely accepted by the scientific community as well as by government regulators.”

Finally, the story implied that benefits people claim for themselves when using probiotics are due to a placebo effect. This ignores the many properly controlled studies directly comparing the effects of specific probiotics to placebos. A positive trial on probiotics, such as observed in this recent trial on irritable bowel syndrome symptoms (here) and in most trials included in Cochrane meta-analyses on prevention of C. difficile-associated diarrhea (here), means that positive effects were observed beyond any placebo effect. The placebo effect is real, equally applicable to probiotics and drugs, but as with all clinically evaluated substances, properly controlled trials control for this effect.

The probiotic field has come a long way over the past 20 years with regard to number and quality of clinical trials. In that time, well-done systematic reviews of the evidence have found benefits for specific probiotics for specific conditions, while also finding a lack of evidence for beneficial effects in other contexts. There are of course well-conducted clinical trials that have failed to demonstrate benefit (here, here, here). This should not be equated to mean that probiotics do not do anything.

Many challenges remain for improving the quality of the evidence across the wide range of different strains, doses, endpoints and populations. More clinical research needs to be conducted in a manner that minimizes bias and is reported according to established standards. Confidence in the quality of commercial products could be improved by industry adopting third party verification (here), and the quality of products targeting compromised populations need to be fit for purpose (here). Companies should stop using the term ‘probiotic’ on products that have no evidence warranting that description. We need to understand much better how a person’s individual situation, such as diet, microbiome, use of medications and fitness, impact the ability of a probiotic to promote health. Much remains to be learned in this evolving and exciting field. As Dr. Merenstein says, “The key question is not, ‘Do probiotics actually do anything?’, as that is easily answered ‘yes’ when you look at robust placebo-controlled trials of specific probiotics. Better questions are ‘Which probiotics do anything, and for what?’”

Further reading:

Misleading press about probiotics: ISAPP responses

ISAPP take-home points from American Gastroenterological Association guidelines on probiotic use for gastrointestinal disorders

New publication gives a rundown on probiotics for primary care physicians

Safety and efficacy of probiotics: Perspectives on JAMA viewpoint

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 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.

 

 

 

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

 

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.

The small intestinal ‘mysteriome’: A potentially important but uncharted microbiome

By Eamonn MM Quigley MD FRCP FACP MACG FRCPI, Lynda K and David M Underwood, Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital, Houston, Texas, USA

 

Over recent years, countless publications have documented the status of the microbiota of the gastrointestinal tract by examining fecal samples. While this approach does provide a “snapshot” or representation of what is going on in the gut, and especially in the colon, it is a crude measure of the complex interactions between micro-organisms in the gut, as well as between these same microorganisms and us (their hosts). Fecal samples comprise a terminal microbial ecosystem, characterized by depletion of readily fermentable substrates, with a concomitant change in microbial composition, even compared to those farther upstream in the colon. It is unlikely, for example, that studies using fecal samples provide a full picture of what happens when bacteria (or other microorganisms) “talk” to the lining of the gut (the mucosa) or interact with the immune system of the intestine. Even less likely is that they provide any insights into bacterial populations in the small intestine, where most of the digestion of food and absorption of nutrients takes place. The small intestine also possesses the most abundant immune tissue of the entire gastrointestinal tract.

Yet, details of which bacteria actually inhabit this long and important organ, the small intestine, are sketchy. This lack of knowledge has apparently not restricted much theorizing and speculation about the role of an overgrowth of colonic-type bacteria (referred to as small intestinal bacterial overgrowth – SIBO) in the small intestine in many symptoms, disorders, and diseases. According to one especially popular theory – the “leaky gut” hypothesis – the list of conditions is nearly endless. The “leaky gut” hypothesizes that dysbiosis in the small intestine (in other words SIBO) and a disruption of the gut barrier leads to “leakage” of bacteria and bacterial products into the circulation causing inflammation, allergy, and autoimmunity.

There are several leaps of faith involved in “leaky gut” including, of course, the definition and diagnosis of SIBO. Traditional methods of diagnosing SIBO (obtaining fluid samples directly from the upper small intestine or a variety of breath tests) are fraught with problems and, in essence, have precluded a universally accepted definition of SIBO.

Fundamental to this dilemma is the definition of the normal small intestinal microbiome – how can we diagnose abnormal when we do not know the limits of normality? I would contend that, while there are situations where it is undoubted (based on the clinical context and various laboratory and other findings) that SIBO is an issue, there are countless more instances where SIBO is over-diagnosed and incorrectly implicated as the cause of an individual’s symptoms. This is an important issue as it can lead to the inappropriate use of antibiotics – something we all wish to avoid.

There is some good news – clever techniques exist for obtaining uncontaminated fluid samples from the small intestine, a capsule technology that permits live sampling of intestinal gases (generated by bacteria) as it traverses the intestine and the application, at last, of high-throughput sequencing, metagenomics, metabolomics, and metatranscriptomics to small intestinal microbiota suggest that the accurate definition of the normal small intestinal microbiome is not far off. At that time, we can all agree on an accurate and clinically meaningful definition of SIBO.

 

Is probiotic colonization essential?

By Prof. Maria Marco, PhD, Department of Food Science & Technology, University of California, Davis

It is increasingly appreciated by consumers, physicians, and researchers alike that the human digestive tract is colonized by trillions of bacteria and many of those bacterial colonists have important roles in promoting human health. Because of this association between the gut microbiota and health, it seems appropriate to suggest that probiotics consumed in foods, beverages, or dietary supplements should also colonize the human digestive tract. But do probiotics really colonize? What is meant by the term “colonization” in the first place? If probiotics don’t colonize, does that mean that they are ineffective? In that case, should we be searching for new probiotic strains that have colonization potential?

My answer to the first question is no – probiotics generally do not colonize the digestive tract or other sites on the human body. Before leaping to conclusions on what this means for probiotic efficacy, “colonization” as defined here means the permanent, or at least long-term (weeks, months, or years) establishment at a specific body site. Colonization can also result in engraftment with consequential changes to the gut microbiota composition and function. For colonization to occur, the probiotic should multiply and form a stably replicating population. This outcome is distinct from a more transient, short-term (a few days to a week or so) persistence of a probiotic. For transient probiotics, it has been shown in numerous ways that they are metabolically active in the intestine and might even grow and divide. However, they are not expected to replicate to high numbers or displace members of the native gut microbiota.

Although some studies have shown that digestive tracts of infants can be colonized by probiotics (weeks to months), the intestinal persistence times of probiotic strains in children and adults is generally much shorter, lasting only few days. This difference is likely due to the resident gut microbiota that develops during infancy and tends to remain relatively stable throughout adulthood. Even with perturbations caused by antibiotics or foodborne illness, the gut microbiome tends to be resilient to the long-term establishment of exogenous bacterial strains. In instances where probiotic colonization or long-term persistence was found, colonization potential has been attributed more permissive gut microbiomes specific to certain individuals. In either case, for colonization to occur, any introduced probiotic has to overcome the significant ecological constraints inherent to existing, stable ecosystems.

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

This leads to the next question: Can probiotics confer health benefits even if they do not colonize? My answer is definitely yes! Human studies on probiotics with positive outcomes have not relied on intestinal colonization by those microbes to cause an effect. Instead of colonizing, probiotics can alter the digestive tract in other ways such as by producing metabolites that modulate the activity of the gut microbiota or stimulate the intestinal epithelium directly. These effects could happen even on short-time scales, ranging from minutes to hours.

Should we be searching for new probiotic strains that have greater colonization potential? By extension of what we know about the resident human gut microbiota, it is increasingly attractive to identify bacteria that colonize the human digestive tract in the same way. In some situations, colonization might be preferred or even essential to impacting health, such as by engrafting a microbe that performs critical metabolic functions in the gut (e.g. break down complex carbohydrates). However, colonization also comes with risks of unintended consequences and the loss of ability to control the dose, frequency, and duration of exposure to that particular microbe.

Just as most pharmaceutical drugs have a transient impact on the human body, why should we expect more from probiotics? Many medications need to be taken life-long in order manage chronic conditions. Single or even repeated doses of any medication are similarly not expected to cure disease. Therefore, we should not assume a priori that any observed variations in probiotic efficacy are due to a lack of colonization. To the contrary, the consumption of probiotics could be sufficient for a ripple effect in the intestine, subtly altering the responses of the gut microbiome and intestinal epithelium in ways that are amplified throughout the body. Instead of aiming for engraftment directly or hand-wringing due to a lack of colonization, understanding the precise molecular interactions and cause/effect consequences of probiotic introduction will lead to a path that ultimately determines whether colonization is needed or just a distraction.

The threat of disease – Ignore science at your peril

By Dr. Karen Scott, University of Aberdeen

We live in an age when life expectancy has increased and many diseases that used to be fatal are curable. Much of this is the result of years of efforts by dedicated scientists, painstakingly working out the causes of diseases, and then the best way to treat or prevent them. Yet the high profile of social media can boost the profile of results from poorly conducted studies, sometimes even beyond the publicity received by the original seminal results. Responsible scientists are partly to blame for this. We are a cagey bunch, frequently suffixing stories about our wonderful successes with caveats, maybes and the recurring refrain “more research is needed”. Those spreading sensationalist publicity have no such qualms.

Take vaccination for diseases caused by viruses. In 1796, Dr Edward Jenner realised that milk parlour girls did not seem to get small pox and theorised that they were protected from the devastating disease due to their continual exposure to the less dangerous cow pox virus. He proceeded to prove his theory by inoculating many people with cow pox, and then exposing them to the small pox virus. Although the experiment would nowadays perhaps be considered unethical, it worked and people infected with cow pox did not get small pox. This heralded the start of vaccination, a huge medical advance that has since protected millions of people from contracting polio, measles, mumps, rabies, tuberculosis and many more devastating diseases. In the 19th Century, Louis Pasteur advanced the method, using inactivated viruses as the inoculation. Vaccination has been so successful that small pox was ‘officially’ eradicated globally in 1979, and the polio vaccine, which was developed in 1955, has led to the virtual world-wide elimination of polio.

But more and more people people are declining to vaccinate their children. The very success of the vaccination scheme may be why it is now in danger. People have forgotten the devastating consequences and lasting effects of these diseases. In the western world it is now unusual to see people crippled by the effects of childhood polio. What about measles? Prior to vaccination, measles was a highly contagious disease, spreading through water droplets in air when an infected person sneezed. Forty percent of those with measles develop complications including pneumonia (which is often the case of measles-related deaths), deafness, blindness and encephalitis (brain swelling), which can even cause brain damage. If the patient survives, the effects of such complications can last for life. Yes – measles, a disease fully preventable by vaccination, kills. I was struck by a recent story about Roald Dahl, whose daughter sadly died after contracting measles when she was seven (see here). In 1986 Roald Dahl wrote an open letter describing his experience, encouraging people to vaccinate their children. The post was illustrated with a picture of a ward full of children suffering from polio, all confined in iron lungs as their breathing had been so badly affected due to paralysis of their chest muscles. No one can want to return to that.

Another contributor to reduced vaccination rates are reports that vaccinations cause more harm than good. Such reports are sustained in part by non-science-based social media claims. Even when original scientific reports are discredited, many parents continue to decide not to vaccinate their children.

How will these “anti-vaccination” parents/carers feel, sitting at the bedside of their critically ill child trying to make sense of the doctor’s explanation that even if their child pulls through, they will never be able to see again? Or explaining to their grown up child that he will never be able to father children due to an almost forgotten childhood disease? All because Mum and/or Dad paid more attention to a campaign on social media with no scientific basis, than to medical advice supported by decades of evidence? Yes, there are instances of people becoming ill with the diseases themselves, or suffering rare side effects of vaccination, but these are rare and pale in comparison to the morbidity and mortality prevented by vaccinations. After all, these same people do not stop driving their car to work when they hear that someone else had an accident doing so. The huge decline in epidemics of viral diseases following the introduction of vaccination programmes speaks to their effectiveness. The vaccine for measles was introduced in 1968 and is estimated to have prevented 20 million cases of measles and 4,500 deaths. In fact the vaccination programme was so successful that it led to the UK being declared ‘measles free’ in 2017.

 

 

 

 

 

 

 

Source – Public Health England; University of Oxford Vaccine Knowledge Project

Yet countries that we travel to on holiday still have measles outbreaks so it is still crucial to get children vaccinated. Even in the US and UK, the large increase in non-vaccinated children means that measles outbreaks (starting with people catching the disease abroad) are becoming more common – evidenced by the second graph above. An alarming statistic is that there are more cases of measles in 2018 than there were in 1998.

Increased numbers of unvaccinated people pose a threat to society at large. Herd immunity can protect a small number of unvaccinated individuals. Indeed, some individuals cannot be effectively vaccinated, including very young infants or when there is a problem with their immune system. But when the number of unvaccinated people rises, these viruses can ‘find’ susceptible hosts and take root once again in the population. This puts our most vulnerable society members at risk. The decision to not immunize is not a victimless decision. We need to maintain vaccination programmes on a global scale, to maintain ‘herd immunity’ and halt the current increase in the numbers of cases occurring.

Bottom line – vaccination works and prevents needless suffering from preventable diseases.

Another day, another negative headline about probiotics?

By Prof. Colin Hill, PhD, APC Microbiome Ireland, University College Cork, Ireland

Scientists have a particular job. We try to discover what is unknown and we want to help to create a better understanding of the underlying forces, both physical and biological, that underpin our amazing universe. It is usually a slow and meticulous process. Gathering data usually takes weeks, or months, or years of work and so there is plenty of time to consider the numerous possible interpretations and the limitations and gaps in our understanding. Everything has to be repeated and subjected to statistical analysis. Finally, we publish our findings and our interpretation of that carefully accumulated data. Even this process takes weeks or months (or years) because of discussions with fellow authors and colleagues, numerous drafts of the manuscript, peer review and editorial comment. We are very aware that whatever we have published will almost certainly be repeated, or built upon, and if we are wrong (in either our data or our interpretation) that it will not withstand the test of time. Thus, we are slow and cautious and often qualify our findings with “this suggests” or “this strongly suggests” and we often finish with the unavoidable conclusion that “more research needs to be done”.

Journalists have a particular job. Journalists have to react quickly, perhaps in minutes or hours, to a breaking story or a commission from their editors, on topics with which they may not be familiar, and write short articles or present short pieces to camera that will appeal to the public and have a clear message. Nuance and complexity must often be left for long-form journalism or that as-yet unwritten novel. Being slow and complete and debating all of the possible interpretations is simply not an option. Finishing up with a cautious, equivocal “on the one hand, but also on the other hand” is also not really an option. Very few journalistic pieces end with “more journalism needs to be done”. It may also be difficult to construct a story along the lines of “some good science was well performed and led to careful and understated conclusions, which should really be repeated before we get too excited”.

It is not surprising then that scientists and journalists can sometimes find themselves at loggerheads. “Do probiotics work?” is a very reasonable question that a journalist can ask a scientist. “Well,” responds the scientist, “that depends on what you mean by ‘work’, and which probiotic you are asking about, and for what condition, and quite often strains are called probiotics but they do not fit the definition, and of course, there was that paper published last year which showed ……”. Cue frustration on both sides. Why can’t the scientist just answer the question? And why can’t the journalist understand that just because a question can be simply stated does not mean that it has a simple answer? Ask a doctor “do pills work?” and you might very well get a similarly convoluted answer, but no one would think it evasive. No wonder the scientist sometimes ends up reading the resultant article in frustration – how did the journalist come to that conclusion, where did all my careful explanations go? Of course, most scientists are imagining his or her scientific colleagues reading the article and wondering at the ‘incomplete’ or ‘trivial’ response. While the journalist may well wonder what planet the scientist lives on if he or she thinks that the editor is going to publish a long essay capturing all of the subtlety of the research.

This almost certainly comes across as me implying that scientists are impeccable purveyors of truth and that journalists are willing to sacrifice truth for simplicity, but I truly am not suggesting that. In almost every instance there is no bad faith involved from either party, it is simply the consequence of the different demands placed on two very different and very valuable roles in society.

So, these things will happen. We will see newspaper articles and online pieces (or editorial comments in journals) that do not contain all the nuance and complexity of the complex paper which it is based. We will see press articles that draw simple and reader-friendly conclusions. “Probiotics quite useless”, “Are probiotics money down the toilet? Or worse?”, etc. So, how should we respond? Do we write erudite articles pointing out the limitations of the commentator, coming across perhaps as arrogant or supercilious? [And yes, of course I use the words erudite and supercilious because it makes me feel better than you.] Do we send angry missives complaining about the article, and perhaps risk drawing further attention to it?

If you are asked by a journalist to comment on a paper, or if your local/national paper or favourite website has published an article that you think is unfair, perhaps the way to respond is to have a few simple questions of your own which can be put to journalists and/or readers. Perhaps we can use a checklist such as the following:

  • Is the article describing an original piece of research and was it published in a reputable, peer-reviewed journal?
  • What evidence is there that the strain or strain mix in question is actually a probiotic? Does it fit the very clear probiotic definition?
  • Was the study a registered human trial? How many subjects were involved? Was it blinded and conducted to a high standard?
  • What evidence was presented of the dose administered and was the strain still viable at the time of administration.
  • Were the end points of the study clear and measurable? Are they biologically or clinically significant to the subjects?
  • Did the authors actually use the words contained in the headline? “Useless”, or “waste of money”, etc?

Once these relatively simple questions are answered, then we can move on to the details and the complexities, but that is not where we should start. Of course, if a study is well performed and reaches a negative conclusion we should absolutely acknowledge that. But we can still point out that one strain or strain mix not working under one set of conditions is only evidence of the fact that one particular strain or strain mix does not work under one particular set of conditions. It does not warrant a blanket condemnation or criticism of all probiotics. Maybe ask the journalist to think about the obvious flaws in the headline ‘Headache pill does not cure cancer, all pills obviously a waste of money!”, and ask why the same standards should not be applied to probiotics?

Scientists and journalists have different roles in society, that is clear, but we can assume a priori that both have clear motives and do not want to mislead readers. Let’s start from there and make it easier for both sides to work together to make the public aware of the very real potential, and very real limitations, of probiotics and prebiotics in preserving health in a society in dire need of practical solutions.

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.

ISAPP Releases New Infographic – Probiotic Checklist: Making a Smart Selection

Not all products labelled “probiotic” are true probiotics. ISAPP just released a new infographic focused on helping consumers make smart selections when examining probiotic products. The infographic addresses identifying products backed by science, effective dosing, and more.

See and download the full infographic here.

See all ISAPP infographics here.

 

science hard blog

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

By Dr. Colin Hill

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

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

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

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

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

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

hill blog industry

Academics working with industry  

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

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

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

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

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

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

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

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

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

Talking Science with ISAPP’s Science Translation Committee

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

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

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

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

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