Microbiota highlights from ueg week virtual 2020

MICROBIOTA, ENVIRONMENTAL AND HOST FACTORS IN HEALTH AND DISEASE

The gut microbiome has been associated with a large number of diseases, but it is still not clear how a healthy or unhealthy microbiome should be defined. A large Dutch population-based study (OP178 R Gacesa et al.) demonstrated common microbial patterns across several diseases (including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), asthma, diabetes and mental disorders), making it possible to define clusters of health- and disease-linked gut microbes and functions. Specifically, the microbiome associated with diseases was found to be characterized by a significant increase in prevalence and abundance of opportunistic pathogens of genera Clostridium, Gordonibacter and Eggerthella, by a reduction in carbohydrate catabolism, synthesis of amino-acid and vitamins, and by an increase in synthesis of long-chain fatty acids. On the other hand, the healthy microbiome showed high abundances of butyrate-producing commensals from genera Alistipes, Roseburia, Faecalibacterium and Butyrivibrio. The authors also showed that the microbiome was primarily shaped by the environment and lifestyle, and therefore concluded that alterations through improving diet, lifestyle and the environment, and use of probiotics can be advocated to improve general health. Furthermore, a longitudinal follow-up study (OP201 L Chen et al.) highlighted that microbial changes over time seem to be driven by environmental exposures and can affect the metabolic health of the host.

MICROBIOTA IN INTESTINAL DISEASES

Lactose restriction is the cornerstone of treating gastrointestinal (GI) complaints in subjects with lactose malabsorption due to lactase deficiency. However, the severity of gut symptoms, such as flatulence, bloating and diarrhea, after lactose intake in these subjects varies substantially, and the reason for this remains unclear. Via analyses from the Dutch Microbiome project (OP177 MDF Brandao Gois et al.), a plausible mediating role of the gut microbiome between dairy intake and the occurrence of gut symptoms in subjects with lactase deficiency was demonstrated, and in particular the Bifidobacterium genus was found to be of potential relevance. Hence, modulating the gut microbiota composition may influence the sensitivity to dairy products in subjects with lactose malabsorption.

Even though the exact mechanisms that explains food-related GI symptoms in patients with IBS remains unclear, different dietary adjustments improves GI symptoms in subsets of patients. A posthoc analysis of a previously published clinical trial (P0786 E Colomier et al.) revealed patterns of psychological, nutritional, and microbial factors that can predict treatment response to both the traditional NICE (National Institute for Health and Care Excellence) diet for IBS and the low fermentable oligo-, di-, monosaccharides, and polyols (FODMAP) diet for specific symptoms. This indicates that individual tailoring of dietary treatment advice in IBS will be possible in the near future.

Gut microbes and their metabolites are involved in the pathophysiology of a number of intestinal diseases, including IBS and IBD, with several abstracts at UEG week 2020 highlighting this. In IBD, a large cohort study nicely confirmed the presence of gut dysbiosis in both ulcerative colitis (UC) and Crohn’s disease (CD) (OP002 A Vich Vila et al.), and that this was translated into the fecal metabolite profile, which could be used as a potential biomarker to distinguish between IBD and non-IBD and between UC and CD. Specifically, metabolites related to sphingolipid synthesis were increased in IBD, whereas fatty acid metabolites were decreased. Furthermore, in a proof-of-concept study (OP045 L Oliver et al.), a combination of four microbiome markers (Faecalibacterium prausnitzii and one of its phylogroups (PHG-II), Ruminococcus sp., and Methanobrevibacter smithii) could predict the treatment response to anti-TNF treatment with a positive predictive value of 100% and negative predictive value of 75%. This indicates that microbiome analyses can be used to personalize treatment in IBD in the near future. The role of gut microbiota in IBS was highlighted in several abstracts, including a study supporting good long-term effects of fecal microbial transplantation in IBS (OP059 M El-Salhy et al.), which was associated with changes in the faecal bacterial and short chain fatty acid profile and increase in enteroendocrine cells (P0783 M El Salhy et al.). Moreover, another study demonstrated a distinct intestinal microenvironmental profile in IBS with a link to the predominant bowel habit of the patient (P0651 C Iribarren et al.), with the separation between IBS and health and among IBS subtypes (IBS with diarrhea versus IBS with constipation) being mostly driven by metabolites involved in e.g. amino acid metabolism and certain cellular and molecular functions. Hence, it seems to be more important what the microbes do than the composition per se. There were also abstracts focusing on animal models of relevance for IBS pathophysiology. These studies highlighted the importance of gut microbiota for the development of abnormal gutbrain interactions (P0052 M Constante et al.), as well as the role of stress in inducing gut dysbiosis and visceral hypersensitivity (OP056 C Petitfils et al.). These studies are of great relevance for our understanding of gut-brain interactions in IBS and the role of gut microbes and their metabolites in these interactions, and fits well into the concept that IBS and other functional GI disorders are now called disorders of gut-brain interactions.

MICROBIOTA IN EXTRAINTESTINAL DISEASES

Finally, there were also studies focusing on the gut microbiome in extraintestinal diseases. Gut microbiome alterations were demonstrated in both renal and liver transplant recipients (OP180 JC Swarte et al., and OP112 y Li et al.). Patients with end stage renal disease were characterized by low gut microbial diversity, increased richness of virulence factors, and antibiotic resistance genes. The microbial diversity decreased further post-renal transplantation and gut microbiota composition was not restored. Furthermore, immunosuppressive agents had a profound effect on gut microbiota composition. The authors concluded that these changes could have far-reaching implications for the outcome of renal transplantation. Similar findings regarding microbial diversity, gut microbiota composition and effect of immunosuppressive agents were noted also in liver transplant recipients, and intriguingly microbial diversity was associated with survival post liver transplantation, therefore revealing a new potential biomarker or therapeutic target.