news probiotics UK

ISAPP works to have evidence-based usage of probiotics to prevent antibiotic-associated diarrheoa implemented in UK

January 12, 2018. Antibiotics are amongst the most commonly prescribed drugs in UK hospitals. However, as well as treating infection they can cause disruption to the gastrointestinal microbiota. This can lead to the relatively common side-effect of antibiotic-associated diarrhoea (AAD) which often delays discharge. More concerning is that a disruption to the normal gut microbiota can lead to reduced resistance to opportunistic pathogens such as Clostridium difficile, leading to C. difficile infection, a potentially severe or fatal infection. Based on the available evidence, probiotics are a safe and effective adjunct to antibiotics to reduce the risk of developing AAD and for the primary prevention of CDAD. The International Scientific Association of Prebiotics and Probiotics has reviewed available data and supports several published assessments, which recommend probiotics as adjunctive therapy for prevention of AAD and CDAD.

This effort was led by Dr. Claire Merrifield BSc MBBS PhD, Speciality Registrar in General Practice, St. Mary’s Hospital, Imperial College Healthcare Trust, Imperial College London and Prof. Daniel Merenstein, MD, Department of Family Medicine, Georgetown University Medical Center and ISAPP Board Member and Treasurer.

Read full recommendation here, which will be sent to NICE and Public Health England.

baby crying colic

ISAPP Digs Deeper into Evidence on Probiotics for Colic with New Meta-Analysis

January 3, 2018.

Evidence exists for gut microbiota differences between infants with and without colic, with one probiotic strain of particular interest therapeutically for colicky infants: Lactobacillus reuteri DSM17938. Discussion groups convened at the 2014 and 2016 ISAPP meetings, both led by Prof. Michael Cabana MD MPH of University of California, San Francisco, and member of ISAPP’s board of directors, focused on the existing randomized, controlled trials and how they might inform medical recommendations.

The discussion group at the 2014 ISAPP meeting in Aberdeen Scotland resulted in a paper describing the individual patient data meta-analysis (IPDMA) protocol, which was published in BMJ Open.  The 2016 ISAPP meeting in Turku Finland culminated in the publication of this IPDMA in the journal Pediatrics: Lactobacillus reuteri to treat infant colic: a meta-analysis. Dr. Valerie Sung, Royal Children’s Hospital, The University of Melbourne and Murdoch Children’s Research Institute, was lead author of this paper, whose coauthors included a team of 11 other experts spanning three continents.

This high quality meta-analysis used individual patient data rather than group means to get a more accurate picture of the efficacy of the probiotic. The paper concluded that L. reuteri DSM17938 is effective and can be recommended for breastfed infants with colic. However, data are lacking for efficacy in formula-fed infants.

“Any single randomized clinical trial involves a great deal of time and resources from investigators, institutions and most importantly, patients. By working together, our team was able to combine data to learn more about the effects of L. reuteri DSM 17983 on the treatment of infant colic. This analysis is a great example of the power of close international collaboration by clinical investigators.”


Probiotics for Colic—Is the Gut Responsible for Infant Crying After All? (Open access through Jan 10, 2018)

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

The Times They Are A-Changin’ With Probiotics

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

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

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

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

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

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

Bob Dylan, Nobel Laureate

The Times They Are A-Changin’

Columbia Records, 1964

probiotics for healthy people infographic

ISAPP releases new infographic: “Probiotics for Healthy People”

November 20, 2017. Probiotics are most commonly studied with for populations with a specific condition—frequent examples include diarrhea, irritable bowel syndrome, and pouchitis. But what kind of evidence exists on probiotics for healthy people?

A new ISAPP infographic gives an overview of what we know about the use of probiotics in healthy individuals. The resource was developed by ISAPP’s Science Translation Committee and approved by  the ISAPP board of directors.

“Studying health benefits in healthy people is a challenge. But there is evidence that probiotics can provide dietary management of some digestive conditions that don’t reach the level of diagnosed disease as well as prevent of some common infectious diseases and. These, and other benefits, are of value to healthy people,” says ISAPP’s Executive Science Officer, Dr. Mary Ellen Sanders. The new infographic  emphasizes it is not necessary to take probiotics to be in good health, but they may serve as a useful addition to a healthy lifestyle.

Research investigating how probiotics can affect healthy individuals through their microbiomes is ongoing in laboratories around the world, and ISAPP continues to track the latest findings.

stethoscope and keyboard

Interpreting Risk Reduction in Probiotic & Prebiotic Clinical Trials

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

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

What type of risk reduction is being reported?

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

Is the risk reduction clinically significant?

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

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

Look for the “Number Needed to Treat”

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

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

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

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


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

salminen and hutkins at YINI

Fermented Foods in Nutrition & Health

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

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

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

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

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

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ISAPP Releases Series of Informational Videos on Probiotics and Health

October 10, 2017. Probiotics are a hot topic—an online search for information yields millions of hits. But how much of this easily-accessible information is scientifically accurate?

The clinicians and scientists serving on the ISAPP Board of Directors constantly receive questions about what’s true when it comes to probiotics and prebiotics. That’s why ISAPP decided to commission a series of four informational videos on probiotics. These videos were overseen by members of our board of directors without input from industry, but industry provided educational grants for their production.

The four new videos focus on these topics:

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

Watch for the videos to roll out during the month of October 2017! They’ll appear here on the ISAPP website video page.

With our mission to advance scientific excellence in probiotics and prebiotics, ISAPP is committed to helping consumers access science-based information on probiotics and prebiotics. To stay up to date on ISAPP news, please sign up for our monthly newsletter!

brain-gut relationship illustration

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

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

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

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

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

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

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

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