关键词: 肥胖小鼠, 胍基乙酸, 高脂饮食, 肠道微生物, 肠道炎症, 炎症性肠病

Abstract: To investigate the effects of guanidinoacetic acid（GAA）on the intestinal tissue pathological morphology and intestinal microbial community structure of obese mice induced by high‐fat diet（HFD），24 C57BL/6J mice were randomly divided into blank control group（Con group），high‐fat diet group（HFD group）and high‐fat diet supplemented with 1% GAA group（HFD+GAA group），with 8 mice in each group. After 12 weeks of feeding，the blood，colon tissue and feces of mice were collected. ELISA was used to detect the expression levels of interleukin‐6（IL‐6），interleukin‐10（IL‐10）and tumor necrosis factor‐α（TNF‐α） in serum and colon tissues. Hematoxylin‐eosin staining and immunohistochemical staining were performed to observe the colon tissue structure and the expression of tight junction proteins，real‐time quantitative PCR（RT‐qPCR） was used to detect the relative mRNA expression levels of inflammatory factors and tight junction‐related genes，and metagenomic sequencing was conducted to analyze the intestinal microbial community structure. The results showed that compared with the Con group，the body weight of mice in the HFD group was significantly or extremely significantly increased，while the colon length and weight were extremely significantly decreased，and obvious structural damage was observed in the colon tissue；after GAA intervention，the above abnormal phenotypes were significantly improved. In addition，the contents of IL‐6 and TNF‐α in the HFD group were significantly or extremely significantly increased，the content of IL‐10 was significantly or extremely significantly decreased，while the HFD+GAA group showed the opposite trend.The results of immunohistochemical staining and RT‐qPCR showed that compared with the Con group，the expression levels of ZO‐1，occludin and claudin‐1 in the colon tissue of mice in the HFD group were significantly or extremely significantly decreased；supplementation with GAA could significantly reverse the above changes.Meanwhile，GAA could improve the species composition of intestinal microorganisms in obese mice，significantly or extremely significantly increase the relative abundances of Firmicutes，Bacteroidota，Bacteroides，Lactobacillus，Eubacterium，Oscillibacter and Parabacteroides，and significantly or extremely significantly decrease the relative abundances of Actinomycetota and Duncaniella.In summary，GAA can improve intestinal inflammation and intestinal pathological damage in high‐fat diet‐induced obese mice by regulating the composition of intestinal microbiota，increasing the abundance of beneficial bacteria，and restoring the expression level of tight junction proteins.

Key words: Obese mice, Guanidinoacetic acid, High‐fat diet, Gut microbiota, Intestinal inflammation, Inflammatory bowel disease