Integrated LC–MS/MS Metabolomics and 16S rRNA Gene Sequencing to Identify Associated Molecular Signatures of Physalis Calyx seu Fructus Against Acute Pharyngitis

Abstract

ABSTRACT This study aimed to characterize the metabolic and microbial alterations associated with Physalis Calyx seu Fructus (PCF) treatment in a rat model of acute pharyngitis (AP). The therapeutic effects of PCF on AP were evaluated by assessing physiological characteristics, analyzing pharyngeal pathological changes and quantifying serum inflammatory cytokines including IL‐1β, IL‐6, and TNF‐α using ELISA. Untargeted metabolomics based on HRLC–MS/MS was applied to plasma and cecal contents, while 16S rRNA gene sequencing served to characterize the gut microbiota within the cecal contents. Spearman correlation and correlation network analysis were applied to explore associations between gut microbiota and metabolites. As expected, PCF intervention significantly alleviated AP‐related clinical symptoms, reduced serum pro‐inflammatory cytokines, and attenuated pharyngeal histopathological lesions. Metabolomics analysis revealed that PCF suppressed elevated plasma lysophosphatidylcholine levels, reversed the excessive accumulation of oxidized lipids in cecal contents, and elevated multiple bile acids. These metabolic alterations were predominantly enriched in the glycerophospholipid metabolism and primary bile acid biosynthesis pathways. Microbiota profiling revealed that PCF selectively enriched Akkermansia , which may contribute to re‐establishing microecological homeostasis. In summary, PCF exerts therapeutic efficacy against AP, potentially linked to the modulation of systemic metabolic profiles, enrichment of beneficial intestinal bacteria, and restoration of intestinal microecological balance.