The American College of Gastroenterology recommends against use of probiotics for primary or secondary prevention of C. difficile

By Prof. Daniel Merenstein MD, Georgetown University School of Medicine and Prof. Eamonn Quigley MD FRCP FACP MACG FRCPI,  Houston Methodist Hospital and Weill Cornell Medical College

The American College of Gastroenterology (ACG) recently published ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. This review considers probiotics for prevention of CDI. The ACG’s recommendations regarding probiotics and C. difficile infection (CDI) are:

  1. We recommend against probiotics for the prevention of CDI in patients being treated with antibiotics (primary prevention) (conditional recommendation, moderate quality of evidence).
  2. We recommend against probiotics for the prevention of CDI recurrence (secondary prevention) (strong recommendation, very low quality of evidence).

The ACG guidelines take a different approach to the evidence relating to probiotics than that of the American Gastroenterological Association (AGA) or the Cochrane Collaboration. The most recent Cochrane review on prevention of C. difficile-associated diarrhea (CDAD) concluded in brief, “moderate certainty evidence suggests that probiotics are effective for preventing CDAD”. In the AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders, the recommendation was:

In adults and children on antibiotic treatment, we suggest the use of S. boulardii; or the 2-strain combination of L. acidophilus CL1285 and Lactobacillus casei LBC80R; or the 3-strain combination of L acidophilus, Lactobacillus delbrueckii subsp bulgaricus, and Bifidobacterium bifidum; or the 4-strain combination of L. acidophilus, L. delbrueckii subsp bulgaricus, B. bifidum, and Streptococcus salivarius subsp thermophilus over no or other probiotics for prevention of C difficile infection. (Conditional recommendation, low quality of evidence.)

In both the AGA and ACG guidelines the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used. How, then, did they come to such different conclusions and recommendations?

The ACG guideline stated,  “a meta-analysis of 19 RCTs that concluded that probiotics were helpful at prevention of CDI in hospitalized patients if given close to start of antibiotics, with a 70% lower risk if probiotics were started within 2 days but falling to a 30% risk reduction if probiotics were started after 2 days of antibiotic therapy”. But then they did not take timing of probiotic administration into account as they assessed the evidence. Instead, they use the negative PLACIDE trial to override all other evidence for primary prevention. The PLACIDE trial was a well-done trial, but participants started their probiotic treatment 3- 7 days after antibiotics. Thus, it would seem that the ACG guideline’s conclusion could favor probiotics as long as they can be started within 2 days of the antibiotic and not recommend against probiotic use.

The ACG guideline objects to combining data on different probiotic strains in meta-analyses in order to provide evidence in favor of probiotics: “Evidence to support probiotics for this indication comes mainly from meta-analyses that pool data from small trials of different probiotic formulations and methodologies.” This is true, but the Cochrane review found thirty-nine studies (8,672 participants) that met their eligibility criteria and it is noteworthy that several different probiotics were found to be effective. The Cochrane number needed to treat (NNT) to prevent CDI is 42. However, if the ACG thought this was driven by too many negative trials, they could have qualified their recommendation. The Cochrane review found in subgroup analyses that probiotics are most effective (NNT=12) among trials with a CDI baseline risk >5%. But to conclude there is no benefit of probiotics for primary CDI is not supported by the evidence.

It is puzzling that ACG insists that the probiotic literature be pooled in a strain-specific manner, yet they support conclusions on fecal microbial transplant (FMT) even though FMT interventions are much more heterogeneous than probiotics in regard to composition and mode of administration. They recommend FMT for treatment of C. difficile based on only three double-blinded randomized clinical trials (here, here and here), only one of which was positive. The positive FMT study was conducted at two sites and compared donor stool (heterologous) versus patient’s own stool (autologous) administered by colonoscopy. Overall, 91% of patients in the FMT group achieved clinical cure compared with 63% in the control group. At site #1, the cure rate with donor FMT was 90.0% (CI, 51.8% to 98.7%) versus 42.9% with autologous FMT, whereas in site #2 the cure rate was essentially identical between the two groups. At site #2, donor FMT cure rate was 91.7% (CI, 57.2% to 98.9%) compared with 90.0% (CI, 51.8% to 98.7%) after autologous FMT. We mention this to question the consistency of evidence standards that the ACG guideline authors impose. They admonish pooled data from small trials of different probiotic formulations and methodologies yet ignore heterogeneity in FMT interventions. The data reviewed for probiotics was primarily from double-blinded randomized trials, while for FMT they rely on case series, uncontrolled studies or retrospective studies.

The authors go on to state, “… high quality evidence to support probiotics for most conditions is scarce.” How do they define “scarce” and “most conditions”? As mentioned, Cochrane found thirty-nine studies (8,672 participants) for prevention of CDAD. Under “summary of evidence”, the authors address issues such as size of the market, regulatory oversight, product cost and quality control problems with commercial products, all of which may reflect practical concerns with some probiotic products in the marketplace, but have nothing to do with available evidence. Furthermore, it is the only intervention where the financial value of the industry and cost of interventions is mentioned. Why are the size of the market or costs for FMT or drugs not just as relevant to this review? Cost is discussed throughout the recommendation but without performing or citing a formal cost analysis or cost-effectiveness analysis, even though there are approaches for doing so to inform evidence-based decision-making (here).

The authors indict probiotics for concerns about safety, citing not the thorough review sponsored by AHRQ and conducted by the RAND corporation that looked at 622 studies and found no statistically significant increased relative risk of the overall number of experienced adverse events (RR 1.00; 95% confidence interval [CI]: 0.93, 1.07, p=0.999), but by referring to a review article that cites case reports of blood infections and refers to one study with microbiota, not clinical, endpoints done in Israel on one commercial product. The data actually show that for well characterized, clinically tested probiotics with high levels of quality control the evidence for infectious complications in non-vulnerable populations is virtually nil. ACG does not mention that FMT was shut down due to safety concerns as soon as the pandemic started.

In summary, we are not convinced that the authors have justified their recommendation against the use of probiotics in relation to CDI prevention. They fail to clarify why the results of their GRADE evaluation of probiotic evidence for prevention of C. difficile resulted in totally different conclusions compared to the AGA document, which found evidence sufficient for conditional recommendation of four probiotic preparations. Further,  the review of evidence for probiotics, whether in terms of efficacy or safety, should be addressed in a manner consistent with other interventions considered and editorializing on issues such as market size, profits and product cost, in the absence of an objective approach using appropriate instruments, should be avoided.

Should the concept of postbiotics make us see probiotics from a new perspective?

By Dr. Gabriel Vinderola, PhD,  Associate Professor of Microbiology at the Faculty of Chemical Engineering from the National University of Litoral and Principal Researcher from CONICET at Dairy Products Institute (CONICET-UNL), Santa Fe, Argentina

In early May 2021 an ISAPP consensus panel  defined postbiotics as “a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host“. The fact that non-viable microbes may still deliver health benefits is not new for the scientific community and was reviewed more than 20 years ago. More recent studies demonstrating health effects of non-viable microbes spurred interest in this topic, leading ISAPP to carefully consider the emerging use of the term ‘postbiotic’ and provide a clear, modern, concise definition.

Postbiotics can be contrasted with probiotics: live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. In practice, probiotics  have likely always coexisted with inanimate microbes, as live microbes will die at all phases of production of a product. In the past, it seems the presence of inanimate microbes as part of probiotic products was not really considered. We all knew they were there, but made a default assumption that they had limited significance. As we consider postbiotics, though, we should perhaps look again at how to address the inanimate components of probiotic products.

The presence of inanimate cells in probiotic preparations: from lab to product

A loop of a fresh, overnight, live culture of a probiotic strain may still contain non-viable cells (Fig. 1). During the biomass production of a probiotic culture, an abundance of live cells can be observed in the exponential growth phase, but as the culture enters the stationary phase, a significant increase in the proportion of non-viable cells occurs (Fig. 2). Yet the culture may display a satisfactory high number of viable cells as verified by traditional plating on agar media. Some years ago, it was reported that a fresh culture of a lactobacilli strain may display a live/dead cells ratio of ca. 100/1. However, this ratio may change to 1:1 after freeze-drying, as studied using flow cytometry, a technology that allows the quantification of both live and dead cells in a culture-independent way. Therefore, a recently freeze-dried culture of a probiotic strain may contain 1010 log CFU/g of live cells, but also the same amount of non-viable cells.

Food supplements may have a shelf life between 12 and 24 months at room temperature and over this time, a proportion of cells will likely lose viability along the shelf life. This depends on the intrinsic resistance of the strain, the nature of the matrix used for freeze-drying, the water activity remaining after lyophilization, the package and the storage conditions. Taking this into consideration, the probiotic supplements industry overfills probiotic capsules or sachets with 1.5 to 4 times more live cells, in order to warrant the delivery at the end of shelf life of the minimum amount of live cells to be able to deliver the expected health benefit. Considering that both freeze-drying and long-term storage may significantly increase the proportion of inanimate microorganisms in a probiotic supplement, a probiotic supplement could easily consist of more inanimate microorganisms than live ones. Yet if the products delivers the minimum amount of live cells to confer a health benefit, this makes the product fit the definition of probiotics so it must be considered a probiotic product. The probiotic focus has been prevalent during previous clinical trials and also during the shelf life of a probiotic product. Maybe we were just overlooking what was going on beyond the information obtained by CFU. These new insights do not change the status of a probiotic, but with due attention given to postbiotic components, offers the possibility to have better and better characterized products in the future.

Figure 1, above – Fluorescence microscopy images of an overnight (18h) culture of bifidobacteria (left) and lactobacilli (right) showing live (green) and non-viable cells (red). The Live/dead BackLight Invitrogen® kit was used for staining cells.

Figure 2, above – Fluorescence microscopy images of a culture of lactobacilli in the exponential (left) and late stationary (right) growth phase showing live (green) and non-viable cells (red). The Live/dead BackLight Invitrogen® kit was used for staining cells.

Are dead probiotics ‘postbiotics’?

What is the contribution of these inanimate cells to the overall health benefit observed for the probiotic culture? In most cases, no evidence exists documenting health benefits of inanimate probiotics. But we may have reason to suspect it may be relevant. For example, a live culture of Bifidobacterium bifidum MIMBb75 significantly alleviated irritable bowel syndrome symptoms and improved quality of life in a double-blind, placebo-controlled study when delivered at 109 CFU, but also the same strain performed equally well for the same end-point when delivered as a heat-inactivated culture. Also, a novel next-generation probiotic strain of Akkermansia muciniphila performed equally well in its live and pasteurized form for improving several metabolic parameters in overweight and obese volunteers. In these cases, it can be said that both strains fit simultaneously the probiotic and the postbiotic definitions.

However, does this mean that as the strain gradually loses viability during storage it gradually becomes a postbiotic? No! This is because method of strain inactivation may play an important role in the health benefit observed. For example, the health benefit delivered by a strain that underwent a heat inactivation can not be assumed to have the same functionality if it is left to die on its own on the shelves. A heat treatment may, for instance, modifiy the spatial display of surface proteins and this may lead to a different immunomodulating capacity of the strain when compared to spontaneous and gradual cell viability lost along storage.

Characterizing probiotic products with an eye to the presence of non-viable cells

By definition, probiotics must be quantified. In the past, this quantification has been limited to numbers of viable cells, typically using a colony count method. This is wholly appropriate, as probiotics must be alive. Yet for the future, will it become necessary to quantify the numbers of non-viable microbial cells as well? With evidence emerging that these non-viable cells may be functional components, then a reasonable argument can be made that this component of a probiotic product should also be quantified. This has implications for characterizing products for use in intervention trials and for the marketplace. The challenge for the marketplace is that probiotic products should deliver the functionality observed in intervention trials.

Reports of trials typically indicate a viable count of the probiotic being tested, but these can be reported in different ways. For example, the statement may indicate delivery of 1.9 × 107 CFU/day of the strain XXX, or delivery of > 1.9 × 107 CFU/day of the strain XXX. These are very different and neither gives any indication of the level of non-viable microbes. The first expression is a specific measure of the viable count at a particular point in time. The second indicates a target minimum and the actual count of viable cells could be much greater. Counts all along the intervention are rarely reported, even though that count could change substantively over time. Papers rarely report if the same batch or different batches of the probiotic preparation were used. The potentially increasing proportion of inanimate microbes is never reported.

In light of postbiotics, future studies should report quantifications of both live and inanimate microbes. Although it is not clear at this time what role inanimate microbes may play in probiotic efficacy, a first step is understanding the composition of probiotic products.

 

ISAPP members can access Dr. Vinderola’s webinar on this topic here. Email info@nullisappscience.org if you require the password.

The future is microbial: A post-pandemic focus on identifying microbes and metabolites that support health

By Prof. Maria Marco, Department of Food Science and Technology, University of California Davis, USA

The COVID-19 pandemic has been a sobering reminder of the significance that microorganisms have on human life. Despite the tremendous scientific and medical advances of the twentieth century, our best precautions against the virus have been to practice the oldest and most simplistic of all public health measures such as washing hands and maintaining physical distance from others. At the same time, the effectiveness of the new SARS-CoV-2 vaccines and the speed in which they were developed show how sophisticated and advanced our understanding of viruses has become. Taken together, the limitations and successes of responses to the pandemic underscore the power of investment in microbiology research. This research, which was first catalyzed by the pioneering work of Louis Pasteur, Robert Koch, and contemporaries in the late 1800s, was the basis for the overall reduction in infectious diseases during the twentieth century. Continued investment in these efforts will prepare us for the next pandemic threat.

Beyond pathogens to health-promoting microbes

As our attention turns to the promise of the New Year, we may also take this moment to appreciate the fact that microorganisms can also do good. Our “microbial friends” were first promoted by the lauded biologists Élie Metchnikoff, Henry Tissier, and Issac Kendall at the turn of the twentieth century. Since then, nearly another century passed before the power of microorganisms to benefit human health reached wider acceptance.

Marked by the emergence of laboratory culture-independent, nucleic-acid based methods to study microbial communities, there is now excitement in the identification of microorganisms that are important for health promotion. This interest is catalyzed by the urgency to find ways to prevent and treat cardiovascular diseases, cancers, and other non-communicable, chronic conditions that are now the leading causes of death worldwide. Much like the pressure to address infectious diseases as the primary cause of mortality prior to the twentieth century, so too is the need today for sustained research investments in studying how certain microorganisms contribute to, or may be essential for, preventing and treating the greatest threats to public health in the modern era.

Exemplified by the growing number of human microbiome studies, it is now broadly understood that the human microbiome contributes positively to digestive, immune, and endocrine systems function. Systematic reviews and meta-analyses of clinical trials support the use of probiotics for a variety of conditions and there are positive associations between the consumption of fermented dairy foods and good metabolic health. To understand how microbes can be beneficial, numerous mechanisms have been proposed (for example, modulation of the immune system and production of neurochemicals that can impact the gut-brain axis), and these mechanisms apply to both autochthonous microbiota and probiotics alike. However, our understanding of exactly how this occurs lags far behind what is currently known about microorganisms that cause harm.

Identifying microbes & metabolites that maintain health

The future of beneficial microbes is in identifying the specific, health-promoting metabolites, proteins, and other compounds that they make. Presently only a handful of such examples are known. Perhaps most recognized are the short chain fatty acids, butyrate, propionate, and acetate, which are known to bind specific human cell receptors to modulate numerous cell pathways including those that affect metabolism. Other microbial compounds generated as intermediate or end products of microbial metabolism (such as metabolites of amino acids), secondary metabolites (such as bacteriocins), and bacterial cell surface constituents (such as certain membrane proteins) were shown to benefit health, although a more complete description of mechanistic details for their effects remains to be discovered. Precise mechanistic descriptions of “beneficial factors”, or the microbial enzymatic pathways and molecules that induce desired cellular and systemic responses in the human body, will be pivotal for elucidation of the precise ways microorganisms sustain health and well-being (for more detail on this topic see here).

Based on what we know about the complexity of the human microbiome and the now many decades of probiotics research, this effort will require innovation and multi-disciplinary coordination. Just as early microbiologists raced to address the high rates of mortality due to microbial pathogens, we are in a new age where again microorganisms are regarded as emerging public health threats. However, we now have to our advantage the knowledge that not all microorganisms cause harm but instead the majority may offer solutions to the greatest health challenges of the twenty-first century.

 

 

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.