Effects of semaglutide on gut microbiota, cognitive function and inflammation in obese mice.

OBJECTIVE: This study aims to investigate the effects of semaglutide on gut microbiota, cognitive function, and inflammation in obese mice. METHOD: Twenty-four C57BL/6J male mice were randomly assigned to three groups: a normal-chow diet group (NCD,  = 8), high-fat diet group (HFD,  = 8), and HFD+semaglutide group (Sema,  = 8). The mice were fed a HFD to establish an animal model of obesity and then administered with semaglutide or saline for 12 weeks. Cognitive function was assessed using the Morris water maze test. Serum pro-inflammatory cytokines were measured. 16S rRNA gene sequencing technology was used to explore gut microbiota characteristics in obese mice. RESULT: Obese mice showed significant cognitive impairment and inflammation. Semaglutide improved cognitive function and attenuated inflammation induced by a HFD diet. The abundance of gut microbiota was significantly changed in the HFD group, including decreased , , _UCG_002, _UCG_014 and increased , , . Whereas semaglutide could dramatically reverse the relative abundance of these gut microbiota. Correlation analysis suggested that cognitive function was positively correlated with and _UCG_014, and negatively associated with and . was positively correlated with TNFα, IL-6 and IL-1β. While _UCG_014 was negatively related to TNFα, IL-6 and IL-1β. CONCLUSIONS: For the first time semaglutide displayed different regulatory effects on HFD-induced gut microbiota dysbiosis. Semaglutide could regulate the structure and composition of gut microbiota associated with cognitive function and inflammation. Thus, affecting gut microbiota might be a potential mechanism of semaglutide in attenuating cognitive function and inflammation.