Introduction Most microbiome studies in inflammatory bowel disease (IBD) are confounded by prior treatment, long disease duration, and inconsistent sequencing/bioinformatic methods—making “core” signatures hard to trust. This systematic review tackles a key unmet question: what does the gut microbiome look like at diagnosis, before therapy starts?
Introduction
Most microbiome studies in inflammatory bowel disease (IBD) are confounded by prior treatment, long disease duration, and inconsistent sequencing/bioinformatic methods—making “core” signatures hard to trust. This systematic review tackles a key unmet question: what does the gut microbiome look like at diagnosis, before therapy starts? The authors go a step further than conventional meta-analysis by reprocessing raw 16S sequence datasets through a single unified pipeline mapped to updated taxonomy, aiming to identify reproducible microbial perturbations in treatment-naïve new-onset Crohn’s disease (CD) and ulcerative colitis (UC).
Summary
Across 36 eligible studies, 18 contributed raw sequencing data for unified reanalysis and 24 contributed to supplementary meta-analysis. The pooled dataset included samples from 1743 individuals (CD, UC, healthy controls, and symptomatic non-IBD controls), with a large proportion of mucosal biopsies. Standard meta-analysis proved unreliable due to extreme methodological heterogeneity, so the central contribution was the unified QIIME2 reprocessing with multivariable modeling (MaAsLin2) adjusting for sample type, age group, geography, and sequencing differences.
Key findings were consistent across CD and UC at disease onset: depletion of obligate anaerobes and enrichment of aerobic, facultative anaerobic, and microaerophilic bacteria, alongside a striking enrichment of orally associated genera in the gut. Importantly, fecal and mucosal biopsy communities were clearly distinct, and geography also shaped community structure—reinforcing why harmonised reanalysis is necessary. The authors interpret the pattern as support for the “oxygen hypothesis” in early IBD—where inflamed mucosa increases luminal oxygenation, disadvantaging anaerobes and enabling oxygen-tolerant and oral taxa to expand.
Clinically, these core signatures may aid earlier diagnosis and risk prediction, and therapeutically they point toward microbiome-targeted strategies—potentially including interventions that alter luminal oxygen availability—especially relevant at diagnosis and in high-risk groups.
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