Temporal strain-resolved metagenomics associates IBD dysbiosis with gastrointestinal inflammation

Abstract

Abstract The gut microbiome in inflammatory bowel disease (IBD) is enriched in proinflammatory bacteria, yet defining a consistent dysbiotic signature is challenging, due to substantial variation between individuals and over time. We performed a high-resolution meta-analysis of 4,839 public metagenomes to disentangle the effects of IBD subtypes, inflammation, temporal, and individual variability. After accounting for temporal variation, we show that IBD-associated dysbiosis was characterized primarily by relative depletion of commensal bacteria rather than expansion of disease-associated taxa, together with increased microbiome variability both within and between individuals. Although 30% of species were IBD-associated, only 73% of these associations remained consistent across all timepoints. IBD-associated bacteria showed reduced persistence within hosts, increased strain loss and diminished strain engraftment. 8% of commensal species displayed strain-level associations with IBD that were independent of species-level changes, suggesting distinct ecological strategies for persistence. Finally, defining an inflammatory index, we demonstrated that inflammation explains much of the observed variation in microbial composition and abundance. Together, our findings indicate that inflammation associates and likely contributes to loss of commensals, thereby limiting microbiome recovery and resilience.