二烯丙基硫醚预处理通过重塑肠道微生物群落并增强微生物相关色氨酸代谢，有效抵御DSS诱导的结肠炎症。

Abstract

DAS pretreatment protected mice against DSS-induced colitis. • DAS restored tight junctions and suppressed inflammatory injury. • DAS reshaped the gut microbiota toward a protective profile. • DAS increased indole-producing tryptophan metabolites, especially IPA and IAld. Ethnopharmacological relevance Allium sativum L. has a long-standing use in traditional medicine for gastrointestinal disorders. Diallyl sulfide (DAS), a key organosulfur compound derived from garlic, exhibits anti-inflammatory activity; however, its specific role in colitis and the underlying microbiota–metabolite mechanisms remain unresolved. Materials and methods Colitis was induced in mice using DSS following DAS pretreatment. Disease severity, intestinal barrier integrity, inflammation, gut microbiota composition, tryptophan metabolites, AhR signaling, colonic IL-22 levels, and STAT3 phosphorylation were evaluated. Fecal microbiota transplantation (FMT), IPA/IAld supplementation, parallel pharmacodynamic comparisons, and AhR blockade with CH223191 were executed to explore the microbiota–metabolite–host signaling axis. Results DAS pretreatment conferred protection against DSS-induced colitis, evidenced by reduced disease activity, preserved colon length, improved histological injury, suppressed inflammatory responses, and restored tight-junction proteins. DAS modified the gut microbiota and elevated local intestinal levels of IPA and IAld. FMT and IPA/IAld supplementation partially recapitulated the protective phenotype associated with DAS, while combined supplementation of IPA + IAld yielded broader protective effects, nearing the protective outcomes provided by DAS. AhR blockade via CH223191 diminished DAS-mediated protection, characterized by decreases in AhR and Cyp1a1 expression, colonic IL-22 levels, and the p-STAT3/STAT3 ratio. Conclusion DAS pretreatment offers prophylactic protection against DSS-induced colitis by altering the gut microbiota and enhancing local indole-producing tryp