Gut Microbiome Signatures at IBD Onset

March 24, 2026

Issue 06

Clinical Question

What core gut microbiome perturbations are present in newly-diagnosed IBD?

Editor’s Bottom Line

Newly diagnosed and treatment-naïve IBD is associated with specific changes in the profile of the gut microbiome. However, it remains unclear whether these changes are causes or consequences of the inflammatory milieu.

Reference

Rimmer P, Zhang F, Scott G, et al. The Gut Microbiome at the Onset of Inflammatory Bowel Disease: A Systematic Review and Unified Bioinformatic Synthesis. Gastroenterology. 2026;170:539-556. doi.org/10.1053/j.gastro.2025.09.014

Synopsis

This multi-center study included a systematic review and a secondary bioinformatic reanalysis of pooled sequencing data from treatment-naïve, newly diagnosed inflammatory bowel disease (IBD) patients. The authors searched MEDLINE, Embase, and the Cochrane Gut register from inception through December 2024 and identified studies including microbiome next-generation sequencing data from patients with newly diagnosed, treatment-naïve IBD. Of 36 eligible studies, 18 included raw 16S rRNA sequence data that was used in the secondary bioinformatic reanalysis, yielding 2,160 samples from 1,743 individuals across 11 countries. The cohort comprised 678 patients with Crohn’s disease (CD), 399 with ulcerative colitis (UC), 130 healthy controls (HCs) and 405 symptomatic controls (SCs), with a total of 990 mucosal biopsy samples analyzed.

Findings from the meta-analysis of published alpha diversity data confirmed prior observations of significant fecal diversity reductions in CD, UC and IBD overall, relative to controls. No significant mucosal biopsy diversity reductions were observed in either CD or UC versus SCs.

There was methodologic variation across the studies, including the use of 12 different DNA extraction kits, 4 types of sequencing platforms, 8 targeted 16S hypervariable regions and 29 distinct analytic pipelines, rendered cross-study meta-analysis largely unreliable, requiring the researchers to perform a unified bioinformatic analysis of the raw sequencing data.

Results of that analysis found a clear separation between fecal and mucosal biopsy communities across disease subtypes. The smallest divergence was observed in UC patients, which was a finding the authors attributed to the more distal nature of UC inflammation and greater mucosal shedding. The geographic origin of patients also significantly influenced microbial community structure, particularly in fecal samples.

Multivariable differential abundance modeling revealed a consistent pattern across both CD and UC: broad depletion of anaerobes, including Alistipes, Roseburia, Agathobacter, Phascolarctobacterium and Bacteroides, alongside enrichment of aerobic, facultative anaerobic, and microaerophilic genera, specifically Pseudomonas, Haemophilus, Schaalia, Enterococcus, Campylobacter and Dialister.

Notably, multiple genera associated with the oral cavity, including Fusobacterium, Peptostreptococcus, Veillonella, Haemophilus and Granulicatella, were consistently enriched across IBD subtypes, geographic regions, and age groups, supporting a theory of oral-gut transmission in newly diagnosed disease.

The depletion of obligate anaerobes with relative enrichment of oxygen-tolerant organisms has not previously been demonstrated so starkly at disease onset across multiple studies, the authors noted. They proposed that targeting luminal oxygen availability may represent a novel therapeutic strategy for new-onset patients and individuals at high risk of developing IBD.

Details

Study Design: Systematic review with secondary bioinformatic analysis of sequencing data
Funding: National Institute for Health Research Birmingham Biomedical Research Centre, The Archie Foundation, Tayside Medical Science Centre
Allocation: Not applicable
Setting: Multicenter
Level of Evidence: 1a