Volume 10 Number 2 2026
Host–Microbiome Co-Evolution in Inflammatory Bowel Disease: Integrative Insights into Genetic Susceptibility, Strain-Level Adaptation, and Immunometabolic Signalling
Muhammad Asif1*, Hafiza Sidra Yaseen2, Pharkphoom Panichayupakaranant3
Integrative Biomedical Research 10 (2) 1-8 https://doi.org/10.25163/biomedical.10210967
Submitted: 11 October 2026 Revised: 01 December 2026 Accepted: 08 December 2026 Published: 10 December 2026
Inflammatory bowel disease (IBD) has long been described as the product of genetic susceptibility acting on an altered gut microbiota, yet the two halves of that statement are usually studied apart. This review argues that they are better read as one process: a co-evolutionary relationship in which host alleles reshape the mucosal niche, and the bacteria occupying that niche adapt to it over evolutionary time. We synthesise thirteen primary and review sources spanning human genetics, population-scale metagenomics, evolutionary strain reconstruction, and functional metabolomics. Three findings anchor the argument. First, susceptibility loci converge on a narrow set of functions — intracellular bacterial sensing, autophagy, cytokine signalling, and leukocyte trafficking — and at least some act by changing which microbes the mucosa tolerates rather than by driving inflammation directly; the CCR5Δ32 data illustrate how modest and phenotype-restricted such effects can be. Second, dysbiosis is not only compositional. Strain-level reconstruction identifies bacterial lineages that diverged millions of years ago and carry genomic innovations suited to an inflamed, oxygenated gut, which means intraspecies variation can matter more than species presence. Third, these shifts are transmitted to the host largely through metabolites — short-chain fatty acids, indole derivatives, and secondary bile acids — acting on defined receptors. We also examine why luminal and mucosal compartments yield different information, and what that implies for biomarkers. Considerable uncertainty remains, particularly regarding causal direction and whether population-level microbial signatures carry individual predictive value. We suggest where the evidence is firm enough to build on, and where it is not.
Keywords: inflammatory bowel disease; host–microbiome co-evolution; strain-level adaptation; short-chain fatty acids; aryl hydrocarbon receptor; CCR5Δ32; precision medicine
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