Significant alteration of gut microbiota in patients with symptomatic uncomplicated diverticular disease

Abstract Mechanisms underlying symptomatic uncomplicated diverticular disease (SUDD) remain unclear. Here, we explored alterations in the gut microbiota associated with SUDD. Patients visiting outpatient clinics for refractory abdominal pain at five Japanese centers between February 2021 and May 2022 were prospectively enrolled. Patients diagnosed with SUDD ( n = 29) and those with diverticulosis but not meeting the SUDD criteria (non-SUDD; n = 35) were included. Asymptomatic individuals served as healthy controls (HC; n = 68). Fecal samples were analyzed using 16 S rRNA gene sequencing. α-diversity indices were significantly lower in the SUDD and non-SUDD groups than in the HC group. β-diversity also differed significantly among groups. The abundance of the Ruminococcus gnavus group was higher in the SUDD group than in the non-SUDD and HC groups, whereas that of Coprococcus was lower. Butyrate-producing bacteria were less abundant in the SUDD group. Prediction-based (PICRUSt2) metagenomic analysis suggested upregulation of pathways, such as exopolysaccharide biosynthesis and cell cycle, in the SUDD group. Patients with SUDD exhibited dysbiosis, which may contribute to pathogenesis via impaired epithelial homeostasis, such as decreased mucosal butyrate concentration. The findings of this exploratory, observational study represent associations that require confirmation via direct functional and metabolomic measurements.