Semaglutide exerts significant modulating effects on intestinal microbiota

The study used 24 male C57BL/6J mice, divided into three groups: a group fed a normal diet (NCD), a group fed a high-fat diet (HFD), and a HFD group treated with semaglutide (Sema). After 12 weeks on the diet, mice in the HFD and Sema groups were treated with daily injections of semaglutide or saline, respectively, for a further 12 weeks. The researchers assessed cognitive function using the Morris water maze (MWM) test, measured levels of inflammatory cytokines in the serum, and analysed the composition of the gut microbiota using 16S rRNA gene sequencing.

The results showed that obese mice (HFD) showed significant cognitive deficits, as well as an increase in inflammatory markers (TNFα, IL-6, IL-1β) compared with mice in the NCD group. Administration of semaglutide (Sema group) not only reduced these inflammatory markers, but also improved cognitive performance compared with the HFD group. Analyses of the intestinal microbiota revealed that HFD-induced obesity was associated with a dysbiosis characterised by a decrease in the abundance of certain beneficial bacterial genera, such as Akkermansia and Muribaculaceae, and an increase in potentially pathogenic bacteria such as Romboutsia and Dubosiella. Treatment with semaglutide reversed these changes, significantly increasing the abundance of beneficial genera and reducing that of genera associated with inflammation.

Correlation analyses showed that cognitive function was positively correlated with the abundance of Muribaculaceae and Clostridia_UCG_014, and negatively associated with Romboutsia and Dubosiella. In addition, Romboutsia was positively correlated with levels of inflammatory cytokines (TNFα, IL-6, IL-1β), while Clostridia_UCG_014 showed a negative correlation with these inflammatory markers.