Qi-Zhi-Wei-Tong granules alleviates chronic non-atrophic gastritis in mice by altering the gut microbiota and bile acid metabolism

Abstract

Ethnopharmacological relevance: In traditional Chinese medicine, Qi-zhi-wei-tong granule (QZWT) significantly reduced the major gastrointestinal and psychological symptoms of functional dyspepsia.

Aim of the study: We aimed to explore the therapeutic effect of QZWT treated chronic non-atrophic gastritis (CNAG) and to elucidate its potential mechanism.

Materials and methods: The composition of QZWT was analysed by UPLC-Q/TOF-MS. The CNAG mice model was established by chronic restraint stress (CRS) in combination with iodoacetamide (IAA). Morphological staining was utilized to reveal the impact of QZWT on stomach and gut integrity. RT‒qPCR and ELISA were used to measure proinflammatory cytokines in the stomach, colon tissues and serum of CNAG mice. Next-generation sequencing of 16 S rDNA was applied to analyse the gut microbiota community of faecal samples. Finally, we investigated the faecal bile acid composition using GC‒MS.

Results: Twenty-one of the compounds from QZWT were successfully identified by UPLC-Q/TOF-MS analysis. QZWT enhanced gastric and intestinal integrity and suppressed inflammatory responses in CNAG mice. Moreover, QZWT treatment reshaped the gut microbiota structure by increasing the levels of the Akkermansia genus and decreasing the populations of the Desulfovibrio genus in CNAG mice. The alteration of gut microbiota was associated with gut bacteria BA metabolism. In addition, QZWT reduced BAs and especially decreased conjugated BAs in CNAG mice. Spearman's correlation analysis further confirmed the links between the changes in the gut microbiota and CNAG indices.

Conclusions: QZWT can effectively inhibited gastrointestinal inflammatory responses of CNAG symptoms in mice; these effects may be closely related to restoring the balance of the gut microbiota and regulating BA metabolism to protect the gastric mucosa. This study provides a scientific reference for the pathogenesis of CNAG and the mechanism of QZWT treatment.

Keywords: Bile acid metabolism; Chronic non-atrophic gastritis; Chronic restraint stress combined with iodoacetamide; Gut microbiota; Qi-zhi-wei-tong granule.