Association of gut microbiome composition and function with colonic diverticulosis

Introduction

Colonic diverticula are outpouchings of the large bowel. As the association between diverticulosis with gut microbiome has been less studied, we aim to characterise the gut microbiome of patients with diverticulosis.

Methods

364 consecutive patients underwent colonoscopy between 2017–2020 at National University Hospital, Singapore. Stool samples were collected prior to colonoscopy. DNA was extracted using FastDNA™ Spin Kit (MP Biomedicals)). Metagenomic libraries were generated using the NEBNext® Ultra™ IIDNA Library Preparation kit and sequenced with the NovaSeq 6000 system (Illumina®). Metagenomic taxonomic and functional profiles were generated using the bioBakery meta’omics workflow. All analyses were performed in R v3.6.2. Microbial diversity indices were calculated using Vegan v2.5. Association analyses were performed using an additive general linear model of log-transformed abundances via MaAsLin2. Statistical significance was corrected for multiple testing with significant associations identified at FDR <0.05.

Results

One third of the subjects (33.8%) had diverticulosis. Subjects with diverticulosis were significantly older (mean age 65.1±7.5 vs 61.3±7.6 years old). There were no significant differences in the microbial diversity amongst subjects with or without diverticulosis. Correcting for age, we identified 16 microbial species and 63 microbial enzymes associated with diverticulosis. There was increased abundance of Ruminococcus species in subjects with diverticulosis, such as R. bromii, R. torques and R. inulinivorans, Subjects with diverticulosis were found with increased microbial L-glutamate metabolism, microbial methanogenesis, fatty acid synthesis, and bile acid dihydroxylation. Those without diverticulosis had have increased 4-aminobutanoate metabolism.

Conclusions

Subjects with diverticulosis have distinct stool microbial signatures. The increased abundance of Ruminococcus bromii amongst subjects with diverticulosis, which is usually associated with increased intake resistant starches, may call to question the traditional concept of a fibre-deficient diet attributing towards diverticulosis.