Bacteroides caecimuris reduces Candida albicans virulence and enhances host antifungal immunity under heat-humidity and high-fat-high-sugar stress.

Prolonged exposure to damp-heat environments coupled with high-fat-high-sugar (HFHS) diets disrupts gut microbiota homeostasis and compromises immunity, elevating risks of enteritis, diabetes, and fungal infections. In this study, We established a murine intestinal infection model by simulating damp-heat conditions (35(±2) C, 90 % humidity), administering an HFHS diet, and challenging with Candida albicans (C.albicans). Mice were treated with Compound Agrimony Enteritis Capsules (FuFangXianHeCao, FFXHC), a traditional Chinese herbal formulation. Gut microbiota profiling (16S rRNA sequencing) and mechanistic studies (in vivo and in vitro) were performed. 16S rRNA analysis revealed that FFXHC treatment enhanced the abundance of the intestinal flora, with a notable increase in the abundance of Bacteroides caecimuris (B.caecimuris)(Compared with 0.11 % in the model group, it increased to 2.9 % after FFXHC treatment). Consequently, B.caecimuris was identified as the dominant flora, and its in-vivo and in-vitro effects on C.albicans were investigated. It was determined that FFXHC treatment could stimulate the proliferation of B.caecimuris. In addition, In vitro qPCR and optical density data and in vivo data show that although B.caecimuris could not inhibit the growth of C.albicans, it could improve the survival status and liver function of infected mice, reduce intestinal inflammation, and reduce the colonization of C.albicans by inhibiting the formation of C.albicans hyphae and reducing its virulence. The B.caecimuris contributed to the differentiation of immune cells and the secretion of immune factors in infected mice, thereby enhancing the immune response and fortifying the host defense. Our study supports a role for B. caecimuris in mediating FFXHC anti-Candida effects, bridging traditional medicine with microbiome-based therapeutics. This study provides mechanistic insights into targeting gut microbiota to combat fungal infections under metabolic stress.