GUT MICROBIOTA AND NUTRITION NEWSLETTER #20
July, 2020
Dear Friends,
It only takes a quick look at any social media platform to see how many people have (re)discovered the joys of fermented foods during the stay-at-home months of the pandemic. If you haven't yet tried to create your own fermented foods, don't be intimidated by those pictures of perfect sourdough loaves! All you need is some extra produce -- radishes, carrots, or even tomatoes -- and you can easily 'kimchi' them or ferment them using a simple salt brine. Fermenters Club is one of our favourite online resources to get you started.
In this July newsletter, we're happy to share some of the best gut microbiota & diet resources we've read lately. The articles span the topics of dyes and emulsifiers in ultra-processed foods, to benefits of the Mediterranean diet and of yogurt consumption. The practice tip this month, from Kristina, concerns the recently released American Gastroenterological Association guidelines on probiotic use.
We hope you enjoy!
Natasha and Kristina
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Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives
Molecules called 'excipients' are present in many foods and drugs. A scientific group led by Peter Turnbaugh screened 136 excipients and found, in particular, that azo dyes (responsible for bright colours in candy, baked goods, and other foods) contain excipients that interfere with drug absorption in the mouse gut. But the good news was that gut bacteria derived from healthy humans metabolized these excipients so they no longer inhibited drug metabolism. This showed the potential of gut bacteria to limit detrimental effects of food and drug additives in the body. Read more here.
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Food additive emulsifiers: a review of their role in foods, legislation and classifications, presence in food supply, dietary exposure, and safety assessment
It is clear that the consumption of ultra-processed foods has been associated with detrimental changes to the microbiota and possible undesirable health effects. As we continue to understand these effects, questions remain around food additives -- in particular emulsifiers -- and how they impact the microbiome. This excellent review provides an update of the role of emulsifiers in food, current typical exposure levels, as well as safety concerns associated with their consumption.
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The Gut Microbiome Modifies the Protective Effects of a Mediterranean Diet Against Cardiometabolic Disease Risk
More and more research supports the health benefits associated with consumption of a Mediterranean diet, especially via impacts on the gut microbiome. This new study from the Harvard T.H. Chan School of Public Health is one of the first studies to demonstrate that greater adherence to a Mediterranean diet is associated with a reduction in cardiovascular disease risk with the beneficial effects being modulated by enrichment in microbes that degrade plant-derived polysaccharides, increase short chain fatty acid production, and play a role in secondary bile acid synthesis. A specific microbial species called Prevotella copri was associated with the greatest reduction in cardiovascular disease risk.
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Association between yogurt consumption and plasma soluble CD14 in two prospective cohorts of US adults
By now we are all aware of the importance of gut health in overall health, but the contribution of diet to maintaining intestinal barrier function is an important issue that continues to be explored. A new study published in the European Journal of Nutrition examined the effect of yogurt consumption on plasma CD14 concentrations. CD14 is a glycoprotein expressed on the surface of immune cells that is associated with intestinal barrier permeability and an over-active immune response to endotoxins. This cross-sectional study examined the yogurt consumption of 1077 individuals and found that high consumption of yogurt (2 cups/week) was associated with lower levels of plasma CD14 concentrations. The effect was stronger in men than in women. The researchers hypothesize that the beneficial health effects often seen with yogurt consumption are a result of improvements in gut barrier function.
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Do the microRNAs we eat affect gene expression?
This Nature Outlook article explores a radical scientific idea: could there be benefits of diet beyond nutrition? This is the unfolding scientific story of dietary microRNAs and whether or not they can directly affect human gene expression. As it turns out, the capsules protecting the precious microRNA cargo, called exosomes (in animal foods) or exosome-like nanoparticles (in plant foods), could have great potential in dietary or drug delivery applications.
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Genome-wide associations of human gut microbiome variation and implications for causal inference analyses
More than 20 research groups got together to do an extensive analysis of genome / gut microbiome associations in multiple participant cohorts. They found associations between host genes and various microbial taxa, which supports the idea that genes contribute to which bacteria are in a person's gut. The researchers caution against assuming causality, however, since environmental factors could confound some of these associations.
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Novel Coronavirus Resource Directory
The amount of new information on COVID-19 is astounding and if you are like us it is difficult to wade through what is and what is not evidence-based. If you are seeking an extraordinary database on evidence-based Covid-19 resources, including everything from clinical guidance to research articles to textbooks, check out the Novel Coronavirus Directory compiled by Elsevier.
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PRACTICE TIP:
Interpreting the American Gastroenterological Association's guidelines for probiotic use
In June, the American Gastroenterological Association published a document called 'AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders'. This document is the result of a multi-year endeavour led by eight gastroenterology experts, who searched and reviewed the evidence that exists for probiotic use for eight different purposes related to digestive health: treatment of C. difficile infection; prevention of C. difficile infection; treatment of Crohn's disease, ulcerative colitis, pouchitis, irritable bowel syndrome (IBS), or acute diarrhea in children; and prevention of necrotizing enterocolitis (NEC) in preterm infants.
Of these eight instances, the group conditionally recommended specific probiotics for three of them: prevention of C. difficile infection, treatment of pouchitis, and prevention of necrotizing enterocolitis in preterm infants (less than 36 weeks gestational age). The guidelines represent very important, painstaking work that provide needed guidance for GI clinicians.
Here's what's important for dietitians to know about these guidelines:
1) Probiotics are not drugs but they are sometimes used in a drug-like manner.
A drug is "a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease". But according the US FDA (and similar regulatory authorities), the probiotics that are currently available on the market are classified as generally recognized as safe (GRAS) foods / supplements rather than drugs. There is a very high safety bar for GRAS substances, since any safety risks that potentially exist cannot be justified or offset by any benefits in treating a disease. These substances need to be safe, period.
The probiotics evaluated in the AGA guidelines are food-like GRAS substances, but still the document evaluates their use in a drug-like manner for specific conditions or diseases, looking for drug-level evidence. This ambiguity exists whenever probiotics are used in medical settings.
2) The guidelines are aimed at gastroenterologists, so they primarily apply to very ill individuals.
Since the guidelines were designed to apply to very ill (or potentially very ill) people that typically receive gastroenterology care, the bar for recommending probiotics was set high. In several of the conditions evaluated, the AGA group found evidence showing that probiotics were effective in the condition, but they decided there was not enough appropriate evidence, or not enough high-quality evidence.
In IBS, for example, the AGA members evaluated two endpoints -- overall symptoms and abdominal pain severity -- and excluded studies on probiotics for other related digestive symptoms, such as occasional diarrhea or constipation, gas, or bloating. So in different situations, such as when someone with IBS sees a dietitian for dietary guidance on mild digestive symptoms, a different bar may exist for recommending probiotics. The clinical decision should take into account the patient's preferences and other factors.
3) In general, the use of probiotics for GI conditions is based on very little mechanistic research.
Most of the time, when probiotics 'work' for a particular GI condition, scientists don't have a good idea of the exact scientific processes by which they work: Normalization of the gut microbiota? Interactions with specific immune cells? Competing for space with pathogens? Reinforcement of the gut barrier? Much is still unknown. So at present, the choice to study specific strains for specific conditions are often based on best guesses about which strains will work.
Further research on the mechanisms of action of probiotics will enable more precise use of probiotic strains for specific medical conditions -- or even for subgroups of individuals who have a medical condition (e.g. people with diarrhea-predominant IBS whose gut microbiota has a certain feature). These next-generation probiotics will be even more powerful tools for prevention or treatment of disease, so stay tuned!
Summary: Dietitians aim to give probiotics when they are warranted and safe, and to avoid them when not warranted or potentially unsafe. The AGA guidelines and similar guidelines by other professional associations around the world are very helpful in providing a basis for recommendations. But ultimately, recommendations should be adapted to your local professional setting and individual patients.
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