Limosilactobacillus reuteri HM108 alleviates obesity in rats fed a highfat diet by modulating the gut microbiota, metabolites, and inhibiting the JAK-STAT signalling pathway

Mi Tang^1,2,3Xianping Li^1,2Jiahui Ren^1,3,4Chunyu Yao^1,3,5Lu Liu^3,4Xiaojing Li^2,3,5Xueping Yuan^3,4,5Junying Zhao^2,3Bin Liu^2,3Weicang Qiao^3,4Lijun Chen^1,4*

• ¹Key Laboratory of Dairy Science, College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang Province, China
• ²National Engineering Research Center of Dairy Health for Maternal and Child, Beijing Sanyuan Foods Co. Ltd., Beijing 100163, China, Beijing, China
• ³Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co. Ltd., Beijing, China
• ⁴National Engineering Research Center of Dairy Health for Maternal and Child, Beijing Sanyuan Foods Co., Ltd., Beijing, China
• ⁵School of Bioengineering, Dalian PolytechnicUniversity, Dalian, Liaoning Province, China

Obesity is a globally prevalent metabolic disease, and high-calorie diets are major contributors to its development. Probiotic interventions can modulate the gut flora and alleviate systemic and low-grade inflammation, making them potential interventions for alleviating metabolic syndrome. This study explored the beneficial effects of the Limosilactobacillus reuteri HM108 strain in breast milk on obesity in high-fat diet-induced specific pathogen-free-grade rats using a multi-gradient concentration intervention experimental design. Six weeks after treatment initiation, serum biochemical markers and inflammatory mediators were determined using enzyme-linked immunosorbent assay. Faecal gut microbiota was assessed using 16S rRNA sequencing. The shortchain fatty acid content was detected using gas chromatography-mass spectrometry, faecal metabolites were analysed using untargeted metabolomics, and the liver tissue was subjected to transcriptomics analysis. The findings indicated that L. reuteri HM108 markedly decreased the serum contents of triglycerides, total cholesterol, lipopolysaccharide, and interleukin-1β; reduced the body weight of the rats; and altered the gut microbiota composition, including reducing the Firmicutes/Bacteroidetes ratio. Limosilactobacillus reuteri HM108 also inhibited the JAK-STAT signalling pathway and ameliorated the synthesis of short-chain fatty acids, lipids, and lipid-like molecules and reduced their associated disruptions in energy metabolism, protein synthesis, and amino acid pathway disorders. Our results provide a theoretical basis for preventing and managing obesity using L. reuteri HM108 treatment.