Based on untargeted metabolomics and metagenomics: a study on the mechanism of Miao ethnomedicine Zingiber mioga (Thunb.) Rosc. in treating slow transit constipation

A rat model of slow transit constipation (STC) was induced by loperamide hydro-chloride to explore the therapeutic mechanism of Zingiber mioga (Thunb.) Rosc. (RH) using integrated metabolomic and metagenomic approaches. Thirty-six Sprague–Dawley (SD) rats were randomly assigned to 6 groups (n = 6): the con-trol group, model group, mosapride-positive control group (2 mg kg−1), and RH low- (1,350 mg kg−1), medium- (2,700 mg kg−1), and high-dose (3,400 mg kg−1) groups. The STC model was established by intragastric administration of lop-eramide hydrochloride (5 mg/kg) for 35 consecutive days, with simultaneous drug intervention. Serum levels of substance P (SP), motilin (MTL), and gastrin (GAS) were quantified; colonic pathological sections were prepared; and serum untargeted metabolomics and fecal metagenomics analyses were conducted. Key findings demonstrated that RH significantly decreased serum SP levels while elevating MTL and GAS levels in STC rats, attenuated colonic pathological lesions, and increased intestinal propulsion rate. Serum metabolomics analysis identified 15 differential metabolites, which were primarily involved in nitrogen metabolism, neuroactive ligand-receptor interaction, and amino acid metabo-lism. Fecal metagenomics analysis revealed that RH restored the Eubacteriales/ Lachnospirales ratio and increased the relative abundance of probiotic genera (e.g., Ruminococcus sp., Eubacterium sp.). In conclusion, RH exerts laxative effects in STC rats by regulating gastrointestinal hormones, mitigating colonic injury, and accelerating intestinal peristalsis. These effects may be mediated by ameliorating amino acid and nitrogen metabolic disorders and modulating gut microbiota composition.