Artemisia rupestris Improves the Microbiota–Barrier Axis in DSS Colitis

Gut microbiota dysbiosis and metabolic disorders are key factors in inflammatory Bowel Disease (IBD) pathogenesis and progression. Although Artemisia rupestris water extract (AR) contains many anti-inflammatory compounds, its effects and mechanisms in colitis have not yet been explored. This study is the first to evaluate AR’s therapeutic efficacy in dextran sodium sulfate (DSS)-induced colitis and to investigate whether AR acts by modifying the gut microbiota and correcting metabolic imbalances. An acute inflammatory bowel disease model was established in mice using 3% DSS. Mice received AR at different doses, and clinical and pathological indices, histopathological scores, and blood concentrations of pro-inflammatory cytokines were evaluated. We explored AR; mechanisms in IBD using 16S rRNA sequencing and untargeted metabolomics. AR decreased concentrations of pro-inflammatory cytokines IL-6, CXCL-1, and TNF-α, and reduced MPO levels. It reduced intestinal permeability and mitigated IBD symptoms. Immunohistochemistry demonstrated that AR downregulated TLR4 and TLR9, while restoring Occludin (OCC) and Zonula Occludens-1 (ZO-1). AR modified the gut microbiota by reducing aberrant taxa such as HT002 and Erysipelatoclostridium, while increasing beneficial bacteria including Bacteroides, Alloprevotella, and Lachnospiraceae_NK4A136_group. AR also rectified metabolic disturbances by reducing 5OH-HIP, reversing decreases in metabolites such as 4-(2-amino-3-hydroxyphenyl)-2,4-dioxobutanoate and vanillin, and influencing amino acid and lipid metabolic pathways. AR treatment produces therapeutic effects distinct from other interventions by targeting inflammatory responses, restoring the gut microbiota and metabolism, suppressing TLR4 and TLR9 signaling, and repairing the mucosal barrier.