Sun Y, Li D, Zhao L, Liu X, Guan K, Ma Y, Wang R, Li Q
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China.
Department of Food Nutrition and Health, School of Medicine and Nutrition, Harbin Institute of Technology, Harbin 150001, China.
J Dairy Sci. 2025 Aug;108(8):7960-7978. doi: 10.3168/jds.2024-26193. Epub 2025 May 30.
Obesity driven by high-fat diets is associated with metabolic dysregulation and gut microbiota disruption. Traditional fermented dairy products, such as Qula from Qinghai Province, China, are valuable sources for isolating novel probiotics with potential therapeutic applications against obesity. This study explored the appetite-regulating mechanisms and gut microbiota modulation by Lacticaseibacillus rhamnosus HF01, a strain isolated from traditional Qula, in mice with high-fat diet-induced obesity. The L. rhamnosus HF01 improved lipid profiles, reduced BW and lipid accumulation, and modulated the hypothalamic expression of appetite-related genes (NPY, POMC), with a particular focus on PYY in appetite regulation. The L. rhamnosus HF01 stimulated PYY secretion through activation of intestinal L cells, which then activated the NPY-Y2 receptor, modulating NPY and POMC expression to regulate appetite. Additionally, L. rhamnosus HF01 reshaped the gut microbiota by increasing the abundance of key short-chain fatty acid (SCFA)-producing genera (Akkermansia, unclassified_f__Muribaculaceae, unclassified_f__Lachnospiraceae, Allobaculum, Candidatus_Saccharimonas). Elevated levels of SCFA, including butyric, isobutyric, and isovaleric acids, correlate with specific microbial taxa and activate GPR41/43 receptors, further promoting PYY secretion. These findings suggest that L. rhamnosus HF01 exerts its antiobesity effects through gut microbiota modulation, SCFA production, and GPR receptor activation, leading to PYY secretion, appetite suppression, and improved metabolic health via the gut-brain axis. The L .rhamnosus HF01 provides a promising therapeutic approach for obesity by targeting the gut-brain axis, regulating appetite through microbiota-driven SCFA production.
高脂饮食导致的肥胖与代谢失调和肠道微生物群紊乱有关。传统发酵乳制品，如中国青海省的曲拉，是分离具有潜在抗肥胖治疗应用的新型益生菌的宝贵来源。本研究探讨了从传统曲拉中分离出的鼠李糖乳杆菌HF01对高脂饮食诱导肥胖小鼠的食欲调节机制和肠道微生物群调节作用。鼠李糖乳杆菌HF01改善了脂质谱，降低了体重和脂质积累，并调节了食欲相关基因（NPY、POMC）的下丘脑表达，特别关注食欲调节中的PYY。鼠李糖乳杆菌HF01通过激活肠道L细胞刺激PYY分泌，进而激活NPY-Y2受体，调节NPY和POMC表达以调节食欲。此外，鼠李糖乳杆菌HF01通过增加关键短链脂肪酸（SCFA）产生菌属（阿克曼氏菌属、未分类的Muribaculaceae科、未分类的Lachnospiraceae科、别氏菌属、假丝酵母单胞菌属）的丰度重塑了肠道微生物群。包括丁酸、异丁酸和异戊酸在内的SCFA水平升高与特定微生物分类群相关，并激活GPR41/43受体，进一步促进PYY分泌。这些发现表明，鼠李糖乳杆菌HF01通过调节肠道微生物群、产生SCFA和激活GPR受体发挥其抗肥胖作用，通过肠-脑轴导致PYY分泌、抑制食欲并改善代谢健康。鼠李糖乳杆菌HF01通过靶向肠-脑轴，通过微生物群驱动的SCFA产生调节食欲，为肥胖提供了一种有前景的治疗方法。
