Exploring the Mechanism of <i>Cinnamomi ramulus</i> in Treating Chronic Atrophic Gastritis Rats Based on Metabolomics and 16S rRNA Sequencing

Cinnamomum cassia Presl. (Cinnamomi ramulus), whose dried twigs are known as Guizhi (GZ), serves as an important traditional Chinese medicine, with its preparations widely utilized in treating chronic atrophic gastritis (CAG). This study aimed to explore its mechanism against CAG rats using integrated approaches. Metabolomics and MetOrigin were applied to analyze its metabolic regulations of gut microbiota. 16S rRNA sequencing and quantification of microbial absolute abundance difference were used to analyze the gut microbiota profiles. Molecular docking was employed to validate the binding affinity between the differential metabolites and key targets. Pharmacological evaluation revealed that GZ effectively improved the pathological features of CAG. Ten metabolites mainly involved in the primary bile acid (BA) biosynthesis pathway in the caecal content were associated with CAG, five of which were significantly restored by GZ. Furthermore, CAG-induced gut microbiota dysbiosis was markedly attenuated by GZ. Specifically, four bacterial phyla and sixteen genera were correlated with CAG, while GZ modulated the abundance of two phyla and five genera. Molecular docking revealed strong binding affinities between differential metabolites and key microbial metabolic proteins (Acmg, bna2, narg, etc.), suggesting spontaneous interactions. Collectively, these findings demonstrate that GZ exerts therapeutic effects against CAG by regulating primary BA biosynthesis and restoring gut microbiota balance.