Reproducible ecological restructuring of the oral microbiome defines the oral-gut axis in Crohn’s disease

Abstract The oral microbiome is increasingly implicated in inflammatory bowel disease (IBD), yet findings across studies remain inconsistent and difficult to reconcile due to methodological heterogeneity. To resolve this, we performed a cross-cohort integration of oral microbiome datasets across 25 studies (n = 1,136 IBD; n = 759 controls), combined with unified re-analysis of publicly available sequencing data and newly generated in-house data within a single bioinformatic framework. Oral microbial diversity was consistently reduced in IBD (standardised mean difference –0.31, p = 0.007), with replication in the harmonised dataset (Hedges’ SMD = –0.372, p < 0.001), driven predominantly by Crohn’s disease (CD). Multivariable modelling identified a reproducible set of genera associated with disease, including enrichment of Corynebacterium , Serratia and Streptococcus . Network analysis demonstrated a fundamental ecological shift: whereas healthy communities were organised around a Selenomonas hub, CD exhibited integration of Corynebacterium into core network architecture, consistent with a shift toward an inflammation-adapted, aerotolerant ecological state. Functional predictions supported this restructuring, with depletion of butyrate metabolism and enrichment of aromatic amino acid degradation pathways. Together, these findings identify reproducible ecological restructuring of the oral microbiome in CD and establish a cross-cohort framework linking oral microbial organisation to the oral-gut axis in IBD. Abstract Figure