Specific alterations in the gut microbiome and metabolome across disease locations of Crohn’s disease: a systematic review

BACKGROUND: Crohn's disease (CD) exhibits substantial heterogeneity in disease behavior and therapeutic outcomes across distinct disease locations. Specific alterations in the gut microbiota and metabolites may drive this variation. This review aims to characterize the distinctive microbial and metabolic signatures across CD phenotypes based on disease location. METHODS: Electronic databases were searched from inception to December 2025 for studies that observed alterations in gut microbiota and metabolites in CD patients with different disease locations. RESULTS: Forty-eight studies including 3,577 CD patients and 2,916 healthy controls (HCs) were analyzed. Ileal Crohn's disease (ICD) was characterized by significant dysbiosis compared with HCs, featuring enrichment of Enterobacteriaceae (especially adherent-invasive Escherichia coli [AIEC]), Fusobacterium and Shigella, alongside depletion of Faecalibacterium prausnitzii, Roseburia and Coprococcus. Patients with colonic Crohn's disease (CCD) exhibited increased levels of Proteobacteria, pro-inflammatory families (Actinomycetaceae, Micrococcaceae) and opportunistic pathogens (Streptococcus, Klebsiella). In contrast, a decrease in short-chain fatty acid (SCFA)-producing families (Lachnospiraceae, Ruminococcaceae) and F. prausnitzii was observed in CCD. Ileocolonic Crohn's disease (ICCD) displayed features combining ICD and CCD elements, with specific depletion in Alistipes communis and enrichment of Shigella flexneri. More pro-inflammatory bacteria were observed in ICD compared with CCD. In terms of metabolic alterations, ICD showed impaired enterohepatic bile acid circulation with excessive fecal loss of conjugated bile acids, while CCD exhibited defective conversion of primary to secondary bile acids. ICCD exhibited both impaired ileal reabsorption and defective colonic transformation. CONCLUSIONS: Our results identified disease location-specific alterations in the microbiome and metabolome of CD, which might be associated with the clinical manifestations and prognosis of different phenotypes.