Even though we have continued to face the consequences of COVID-19 in 2021, that has not prevented the emergence of relevant advances around the gut microbiome. The latest research in the field focus on: a better understanding of how gut microbiome-targeted diets improve immune status; the potential of targeting the mycobiota and bacteriophages for treating gastrointestinal diseases; new candidates for next-generation probiotics; an updated definition of postbiotics; and clinical trials demonstrating the efficacy and safety of microbiota-based live therapeutics for reducing the recurrence of Clostridioides difficile infection.
So let’s take a closer look at some of the breakthroughs witnessed in 2021.
Plant-based fiber and fermented foods may have a positive impact on immune status in healthy adults
The COVID-19 pandemic has led to increasing interest in the role of diet for ‘immune boosting’, yet few dietary intervention studies have looked at changes in immune markers resulting from an intervention.
A recent prospective, randomized multi-omics study showed a diet rich in fermented foods or high levels of plant-based fiber may shape immune status and gut microbiome function in healthy adults.
Six servings a day of fermented foods—including yogurt, sauerkraut, kefir, kombucha and kimchi—led to increased gut microbiome diversity, altered microbiome composition and decreased levels of inflammation markers. On the other hand, the subjects who doubled their fiber intake from about 22 grams to 45 grams a day had an increased expression of glycan-degrading enzymes and some reductions in inflammation, the latter being apparent in participants who started out the study with higher levels of microbial diversity.
A diet rich in fermented foods or high levels of plant-based fiber may shape immune status and gut microbiome function in healthy adults
Although the findings of the 10-week study show how a diet rich in fiber or fermented foods influences the gut and inflammation, participants did not report feeling any different when the study ended. Finding out the extent to which the findings relate to specific health outcomes will therefore require follow-up interventional studies.
As we continue to get a better understanding of how non-pathogenic microbes found in food impact health through their effects on the gut microbiota, scientists have suggested that it would be a good idea to adapt the concept of a Recommended Dietary Allowance to safe live microbes, in addition to the existing RDAs for macronutrients, vitamins and minerals.
Key studies suggest the potential of gut fungi and bacteriophages for treating gastrointestinal diseases
While the gut microbiome is dominated by bacteria, other microorganisms such as fungi and phages are also present. Scientists are just beginning to investigate the role of the overlooked fungal component of the microbiota, namely the mycobiota, in digestive diseases such as inflammatory bowel disease.
New studies show food-associated Candida species such as Debaryomyces hansenii, which is enriched in inflamed tissue in patients with Crohn’s disease, prevent wound healing in mice by turning protective macrophages into macrophages expressing the chemokine CCL5 that impair wound healing, which is, in itself, affected in IBD. Furthermore, targeting Candida albicans adhesins and secreted virulence factors that are dysregulated in patients with Crohn’s disease is another mechanism by which the gut mycobiota can shape host immunity.
The findings suggest that specific diets aimed at excluding pro-inflammatory foods and restoring microbial diversity could help induce and maintain remission in IBD, highlighting the need for further research on precision nutrition in patients with IBD. A major translational advance in targeting the gut mycobiota in IBD was the finding that, in mouse models, an engineered Saccharomyces cerevisiae regulates levels of pathogenic metabolites in the gut, providing protection against colitis.
Specific diets aimed at excluding pro-inflammatory foods and restoring microbial diversity could help induce and maintain remission in IBD
For further information, you can check out this review article in Nature Reviews Gastroenterology & Hepatology summarizing the implications of mycobiota-host immune interactions in the context of IBD management.
Beyond gut fungi, recent discoveries have revealed the potential of gut bacteriophages for treating inflammatory bowel disease and chronic liver disease, with patients with those conditions showing a distinct phageome composition. Nonetheless, there are major challenges involved in manipulating the gut microbiota with phages, which include safety issues related to phages’ interaction with human immune cells and the narrow host range receptors that limit their therapeutic utility.
Beyond traditional probiotics: next-generation probiotics candidates identified for targeting functional dyspepsia and obesity
To date, the most widely studied strategies for targeting gut microbes have involved diet, prebiotics and transferring microbes either in the form of entire microbial communities (via fecal microbiota transplants) or a single microorganism or defined microbial consortia (via probiotics). In 2021, we have learned that some strategies for altering the gut microbiota may work better together than alone, such as in the case of supplementing low fermentable fiber after FMT to improve insulin sensitivity in individuals with severe obesity.
When it comes to probiotics, species other than Lactobacillus and Bifidobacterium are being explored as candidates. According to a pilot, double-blind, randomized controlled trial, treatment with Bacillus coagulans MY01 and Bacillus subtilis MY02 with a maltodextrin prebiotic for 8 weeks reduced symptoms of functional dyspepsia involving a suppression of Th17 signaling in blood, increased Faecalibacterium in stools and reduced small intestinal bacterial overgrowth.
As for obesity, the newly discovered bacterium Dysosmobacter welbionis, which is highly prevalent in the human gut, showed potential for counteracting some obesity-related outcomes.
Bifidobacterium longum APC1472 is another promising probiotic that showed potential for helping with reducing specific markers of obesity and conditions of heightened blood glucose, such as type 2 diabetes.
The newly discovered bacterium Dysosmobacter welbionis showed potential for counteracting some obesity-related outcomes
Although postbiotics are not new to the scientific literature, they represent a novel concept in the field that require a scientific consensus that adds clarity. A group of experts under the auspices of the International Scientific Association for Probiotics and Prebiotics has updated the definition of postbiotics to “preparations of inanimate microorganisms and/or their components that confer a health benefit on the host”. The potential clinical effects of postbiotics include preventing common respiratory and gastrointestinal infections, alleviating irritable bowel syndrome symptoms and abrogating the negative effects of stress.
New clinical trials show the efficacy and safety of microbiota-live biotherapeutics in reducing recurrence of C. difficile infection
- difficile infection (CDI) is still the most common type of healthcare-associated infection and hospital-associated diarrhea, leading to substantial mortality and morbidity. In parallel with the identification of clinical, immunological and microbiological predictors of poor outcomes in C. difficile infection, major advances have been made regarding the use of microbiome therapeutics, in the form of entire microbial communities (via fecal transplants) or purified bacterial spores.
- difficile is one of the few ailments for which microbiome treatments in the form of fecal microbiota transplants are supported by solid scientific evidence. In that regard, new clinical data presented in 2021 showed that a broad consortium of live microbes administered via enema and a consortium of purified Firmicutes spores reduced the risk of recurrent C. difficile infection with a good safety profile.
In the current context of COVID-19, screening of donors for severe acute respiratory syndrome coronavirus 2 is recommended, following reports of several patients with CDI developing systemic infection with antibiotic-resistant bacterial infections following FMT and taking into account concerns about possible infections with SARS-CoV-2. In that regard, a guidance document has been published on FMT during the COVID-19 pandemic.
The importance of language and communication in microbiome research
Last but not least, as microbiome research continues to make progress, it is also important that significant discoveries are properly communicated to the lay public to avoid overhype and misunderstandings.
Words matter in the gut microbiome field. For instance, one particular inexactitude in microbiome research is the concept of ‘dysbiosis’, which implies an abnormality in the gut microbiome that it is not always harmful. In addition, scientists are not sure yet about what a healthy or normal microbiome actually means. As such, terms such as ‘altered’, ‘changes’ or ‘different’ are preferred over dysbiosis.
The closely related terms “fiber”, “microbiota-accessible carbohydrates” and “prebiotics” provide another area of confusion. Fiber is a broad umbrella that includes microbiota-accessible carbohydrates (MACs) and prebiotics. While both prebiotics and MACs are utilized by the gut microbiota, not all MACs are considered prebiotics and the latter is reserved for substrates selectively used by gut microbes with scientific evidence to support their health effects.
Although we missed out on holding the Gut Microbiota for Health World Summit due to COVID-19 restrictions, we are planning to hold the 10th edition of the GMFH World Summit in Washington, D.C. and via livestream in March 2022.
After that retrospective, that’s all that is left to do now is to wish you a very happy 2022! Don’t forget to stay tuned over the coming year for more relevant gut microbiome-related reading and resources to support your everyday clinical practice!
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