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.