Microbial associations with Microscopic Colitis

ABSTRACT BACKGROUND AND OBJECTIVE Microscopic colitis is a relatively common cause of chronic diarrhea and may be linked to luminal factors. Given the essential role of the microbiome in human gut health, analysis of microbiome changes associated with microscopic colitis could provide insights into the development of the disease. METHODS We enrolled patients who underwent colonoscopy for diarrhea. An experienced pathologist classified patients as having microscopic colitis (n=52) or controls (n=153). Research biopsies were taken from the ascending and descending colon, and the microbiome was characterized with Illumina sequencing. We analyzed the associations between microscopic colitis and microbiome with a series of increasingly complex models adjusted for a range of demographic and health factors. RESULTS We found that alpha-diversity was significantly lower in microscopic colitis cases compared to controls in the descending colon microbiome. In the descending colon, a series of models that adjusted for an increasing number of co-variates found taxa significantly associated with microscopic colitis, including Proteobacteria that was enriched in cases and Collinsella enriched in controls. While the alpha-diversity and taxa were not significantly associated with microscopic colitis in the ascending colon microbiome, the inference p-values based on ascending and descending microbiomes were highly correlated. CONCLUSION Our study demonstrates an altered microbiome in microscopic colitis cases compared to controls. Because both the cases and controls had diarrhea, we have identified candidate taxa that could be mechanistically responsible for the development of microscopic colitis independent of changes to the microbial community caused by diarrhea. Significance of this study What is already known about this subject? Microscopic colitis is a common cause of chronic diarrhea. The exact etiology of microscopic colitis is unknown, but the gut microbiome is considered to play an important role. Prior studies have reported microbial changes associated with microscopic colitis, but the results are not consistent. Prior studies have generally involved small numbers of patients, fecal samples, and comparison to healthy controls. What are the new findings? The microbiome was altered in microscopic colitis patients. Microscopic colitis was associated with lower alpha-diversity, increase of inflammation related taxa and decrease of Collinsella in the descending colon microbiome independent of diarrhea status. The changes of microbial features were consistent between ascending and descending colon microbiomes, but with smaller changes in the ascending colon microbiome. How might it impact on clinical practice in the foreseeable future? The altered microbial communities in patients with microscopic colitis suggest that the patients might benefit from prevention or treatment with live biotherapeutic products.