Baicalin and levofloxacin exert divergent modulation on gut microbiota and metabolome crosstalk in DSS-triggered ulcerative colitis

Baicalin (BA), a bioactive flavonoid, and levofloxacin hydrochloride (LH), a fluoroquinolone antibiotic, both hold potential for ulcerative colitis (UC) treatment, yet the mechanistic differences in their regulation of gut microbiota and metabolome remain elusive. This study aimed to systematically compare their therapeutic efficacy and underlying mechanisms in a dextran sulfate sodium-induced murine colitis model, with a focus on gut microbial and metabolic modulation. Mice were randomized into Control, model, BA-treated, and LH-treated groups. Disease severity was assessed via body weight changes, disease activity index, colon length, and histopathological analysis. Western blot and enzyme-linked immunosorbent assay were employed to detect NF-κB pathway activation and pro-inflammatory cytokine levels, while 16S rRNA sequencing and metabolomics profiled gut microbiota and metabolites. Both agents markedly ameliorated colitis symptoms, suppressed NF-κB activation, and cytokine expression, with BA showing superior cytokine inhibition. BA enriched beneficial Lactobacillus , regulating isoflavone/alkaloid synthesis; LH elevated Akkermansia abundance and modulated amino acid metabolism. These findings reveal distinct therapeutic mechanisms of BA and LH, laying a foundation for personalized UC therapy and validating BA’s traditional medicinal utility.