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With current advances in medicine and nutrition, a transition is taking place from a one-size-fits-all approach towards personalized therapy. Indeed, the close link between host and gut microbiota, as well as with the environment in which those two elements evolve, makes each patient a unique case. Dr. Purna Kashyap exemplified the problem of the huge variability in patient response to treatments with irritable bowel syndrome, where, for instance, patients with IBS who have symptoms of diarrhea have a very different gut microbiota compared to those who are constipated. Furthermore, every individuals relapse profile is different.
The gut-brain axis is the two-way link between the gastrointestinal tract and the brain. In fact, chronic stress can impact the gut microbiota to the point of increasing the likelihood of irritable bowel syndrome and decreased gut microbiota health in general. Dr. Emeran Mayers work focuses on cognitive behavioral therapy, by teaching patients relaxation strategies such as progressive muscle relaxation, controlled breathing and hypnosis to treat irritable bowel syndrome symptoms. The correlation between the gut microbiota of patients with IBS and response to cognitive behavioral therapy is being studied by Dr. Mayers team. So far, findings have shown that gut microbiome profiles could predict which patients with IBS would respond to cognitive behavioral therapy.
To continue with the gut microbiotas role in disease treatment, the summit welcomed Dr. Jennifer A. Wargos team, which is working on how bacteria in tumors can affect chemotherapy or immunotherapy. In two of their findings, they noticed that the gut microbiota can modulate the toxicity of cancer therapy and found that people who respond to immunotherapy have a greater gut microbiota diversity, which is related to eating a high-fiber diet. Thus, gut microbiota-targeted interventions may help improve treatment responses in patients with low remission diseases such as metastatic melanoma.
As the gut microbiota is part of our system and forms a symbiosis with the host, bacteria will react to food intake, blood glucose level and circadian cycle. In the context of diabetes prevention and treatment, Dr. Purna Kashyap showed that, based on a persons gut microbiota profile, blood glucose levels following food intake can be predicted.
The circadian cycle is what allows us to fall asleep at night and get up in the morning. Stimuli such as light, sun exposure and food intake regulate that cycle. Dr. Dirk Haller and his team showed that 15% of the gut microbiota follows the same rhythm. Furthermore, by studying patients with type 2 diabetes and their gut microbiota, they found that the gut microbiota of those patients lost its rhythmicity.
Studies on identical twins help scientists understand the effect of diet and environment on gut microbiota. Strikingly, there is a wide variation in gut microbiota from person to person and only 37% of the same gut microbes are shared by identical twins still living together, making diet responsible for that variation. The current challenge presented by Dr. Nicola Segata is that there are many ways of analysing the food consumption of individuals: according to food items, food groups, nutrients or dietary patterns. In that regard, Dr. Segatas team has found a strong association between unhealthy food (high in sugar and saturated fat) and specific bacteria and obesity, high body mass index and cardiometabolic diseases, while healthy food (vegetables, non-transformed products) was mostly associated with the beneficial bacteria Prevotella copri.
Thanks to the high number of studies on the effect of diet on the intestinal microbiota, we know that the gut microbiota is highly malleable. In other words, after only 24 hours of a change in diet, the microbiota will be different. It is also highly resilient, which implies that if changes in diet do not persist, the intestinal microbiotas composition will return to its original state in less than 24 hours.
Dr. Rachel Carmody brought up an interesting point at the summit about how certain foods are better absorbed by the host when eaten cooked than when raw and that heat inactivation of antimicrobial compounds in food may also play a role in foods impact on gut microbes. Some foods appear to be better digested cooked than raw, which could be explained by the long period during which fire has been part of human evolution. In addition, raw food not absorbed by the host will be fermented by bacteria, which will then bring calories to the host, in what is known as energy return.
Food intake, digestion and gut microbiota are linked and work together. For instance, the body secretes bile acids during digestion to absorb any fat that has been consumed. Dr. Sloan Delvin is interested in how the gut microbiota can assimilate bile acids and change their conformation, as well as their effect on health. Furthermore, by converting those bile acids, some bacteria also have anti-inflammatory and anti-infectious properties.
Dr. Dan Knights and his team looked at the evolution of the composition of the intestinal microbiota in second-generation immigrants to America. It is known that gut microbiota diversity and richness in individuals living in Westernized countries are much lower than in those living in developing countries. It was therefore interesting to note that even though the diets of second-generation immigrants did not vary that much from the diets consumed in their countries of origin, the environment in which they livewith antibiotics, pesticides, C-sections and infant formulacan lead to a reduction in gut microbiota diversity and richness to the same level as the American population. In Dr. Knightss study, it appears that diet explains only 4% to 6% of gut microbiota variation, which means that the Westernized lifestyle of second-generation immigrants has a huge impact on their gut microbiota. It is also important to keep in mind that foods are more than just nutrients and are composed of many molecules that vary from one food to another, thus shaping the gut microbes in a different way.
Dr. Gary D. Wu focused on how to reduce symptoms in patients with inflammatory bowel disease using diet. His research team compared three diet options: vegan, omnivorous and exclusive enteral nutrition. A vegan diet seems to reduce symptoms and the duration of flare-ups compared to an omnivorous diet but, interestingly, exclusive enteral nutritionliquid food containing 0% fiberis the gold-standard diet for patients with IBD. However, it has been shown that exclusive enteral nutrition slows gut microbiota recovery and alters carbohydrate and amino acid gut metabolites.
As your knowledge about the gut microbiota develops, it will come as no surprise to readers that the most common probiotics are based on the Lactobacillus and Bifidobacterium species. However, Dr. Phillippe Langellas team is now working on next-generation probiotics, which include both new species of bacteria such as F. prausnitzii, which has been found to have anti-inflammatory properties, and genetically modified lactic acid bacteria, which can deliver key components to host cells to mediate inflammation in IBD patients or restore healthy gut function.
Similarly, Dr. Eric Alms team found that certain strains of Lactobacillus probiotics could reduce salt-induced hypertension and that the presence of F. prausnitzii was higher in patients who did not have diarrhea after taking antibiotics.
Fecal microbiota transplantation and its beneficial healing effect under certain conditions was discussed during the session, with information shared about how transplantation of the intestinal microbiota is not yet safe and does not cure everyone of diseases beyond Clostridioides difficile infection.
By creating a predictive model, Dr. Eric Alms team can tell what a patients gut microbiota composition will look like after receiving a gut microbiota transplant from a specific donor, allowing doctors to find the ideal donor for each patient. Interestingly, patients colonized with new species of bacteria from a donor are more likely to be colonized with bacteria belonging to the same species from their own environment. The team found that two distinct species from a single donor were more similar than the same two species from different donors. That could be explained by the fact that in the environment, gut bacteria communicate and exchange information via gene transfer. The team also found that gene transfer from one bacterium to another occurs more in Western populations.
Currently in clinical trials, defined microbiome therapeutics can be given with or without prior antibiotic treatment, in one or more doses, with a mixture of donor stool or a pool of freeze-dried Firmicutes. Defined microbiome therapeutics can be used for other pathogenic infections, such as the Klebsellia infection studied by Dr. Kenya Honda. Through impressive work that screens stool from several donors and then specific bacteria, and then individually identifies the necessary bacteria among the dispensable species, Dr. Honda and his team hope to find a new treatment. The preliminary evidence on the effect of defined microbiome therapeutics on pathogen infection suggests their potential use in ulcerative colitis, food allergy and some cancers, among others.
One of the most exciting topics currently under study is the connection between the gut microbiota and the COVID-19 virus. During the pandemic, many researchers have tried to identify factors that explain the severity of symptoms and side effects associated with vaccination. Dr. Siew C. Ng presented the results of studies showing that people with type 2 diabetes and obesity, as well as the elderly, were at risk of developing more severe symptoms from COVID-19. Interestingly, those individuals also have an altered gut microbiota, which would affect immune system responses and therefore the severity of COVID-19 symptoms.
The researchers also found that people with adverse effects from the vaccination had a distinct gut microbiota profile from those without symptoms. Armed with that observation, the researchers are now focusing on restoring the health of the gut microbiome through fecal microbiota transfer, diet and probiotic administration. It is difficult to have a definite answer in such a short period of time, but in the meantime, the one piece of advice remains: follow a healthy diet!
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What's the latest in gut microbiota science? Some insights from this year's GMFH Summit - Gut Microbiota for Health
