A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients

TLDR

Inflammatory bowel disease is a chronic gastrointestinal inflammatory condition linked to alterations in the gut microbiome. The study aimed to identify strain‑specific functional correlates of IBD outcomes by performing metagenomic sequencing of monthly stool samples from 20 IBD patients and 12 controls. Researchers profiled taxa with MetaPhlAn2, functions with HUMAnN2, identified differentially abundant species via MaAsLin, analyzed strain‑specific pangenome haplotypes with PanPhlAn, and expanded the R. gnavus pangenome by sequencing nine patient isolates.

Abstract

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that is associated with changes in the gut microbiome. Here, we sought to identify strain-specific functional correlates with IBD outcomes.We performed metagenomic sequencing of monthly stool samples from 20 IBD patients and 12 controls (266 total samples). These were taxonomically profiled with MetaPhlAn2 and functionally profiled using HUMAnN2. Differentially abundant species were identified using MaAsLin and strain-specific pangenome haplotypes were analyzed using PanPhlAn.We found a significantly higher abundance in patients of facultative anaerobes that can tolerate the increased oxidative stress of the IBD gut. We also detected dramatic, yet transient, blooms of Ruminococcus gnavus in IBD patients, often co-occurring with increased disease activity. We identified two distinct clades of R. gnavus strains, one of which is enriched in IBD patients. To study functional differences between these two clades, we augmented the R. gnavus pangenome by sequencing nine isolates from IBD patients. We identified 199 IBD-specific, strain-specific genes involved in oxidative stress responses, adhesion, iron-acquisition, and mucus utilization, potentially conferring an adaptive advantage for this R. gnavus clade in the IBD gut.This study adds further evidence to the hypothesis that increased oxidative stress may be a major factor shaping the dysbiosis of the microbiome observed in IBD and suggests that R. gnavus may be an important member of the altered gut community in IBD.