Medicine-food homologous citrus species alleviate high-fat-diet-induced obesity via modulation of the gut microbiota.

The rising prevalence of obesity underscores the need for safe, sustainable dietary interventions. Medicine-food homologous (MFH) citrus species possess nutritional and pharmacological potential, yet their functional diversity remains unclear. This study characterized the phytochemical profiles of five MFH citrus species (Daidaihua, Foshou, Huajuhong, Xinhui Chenpi, and Xiangyuan) and evaluated their comparative effects on the gut microbiota and obesity in healthy and high-fat-diet (HFD)-induced obese mice. High-performance liquid chromatography (HPLC) analysis revealed eight characteristic compounds, including three flavanone-O-glycosides (naringin, hesperidin, and neohesperidin), three polymethoxyflavones (PMFs; nobiletin, tangeretin, and 5-demethylnobiletin), one flavanone aglycone (naringenin), and one coumarin (5,7-dimethoxycoumarin), with each species exhibiting a distinct profile. All MFH citrus extracts were found to modulate the gut microbiota by increasing diversity, enriching beneficial genera (e.g., Akkermansia), and suppressing the opportunistic pathogen Staphylococcus. Metabolically, all MFH citrus extracts significantly lowered fasting or random glucose, although dynamic glucose tolerance was not significantly improved; Daidaihua, Huajuhong, and Xiangyuan reduced serum triglyceride levels, while Foshou increased serum HDL-C levels as well as inhibiting weight gain and white adipose tissue accumulation. The identified characteristic compounds are likely responsible for the observed bioactivities. These findings suggest species-specific metabolic benefits potentially linked to gut microbiota modulation of MFH citrus, providing a preliminary basis for the targeted development of citrus-derived functional foods for personalized nutrition.