2024-08-19
Semaglutide exerts significant modulating effects on intestinal microbiota
Gastroenterology and Hepatology
The article entitled ‘Effects of semaglutide on gut microbiota, cognitive function and inflammation in obese mice’ explores the impact of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, on gut microbiota composition, cognitive function and inflammation in obese mice fed a high-fat diet. Conducted by a team of researchers in China, this study aimed to understand how semaglutide could modulate the intestinal microbiota and thus attenuate the cognitive deficits and inflammation associated with obesity.
Semaglutide, a drug commonly used to treat obesity and type 2 diabetes, has been shown to have beneficial effects on weight regulation and improved metabolic function. However, its influence on the intestinal microbiota, and consequently on cognitive function and inflammation in obese individuals, remains to be clarified.
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.
These results suggested that semaglutide could improve cognitive function and reduce inflammation by altering the composition of the gut microbiota, favouring a reduction in pro-inflammatory bacteria and an increase in beneficial bacteria.
This study provides new evidence that semaglutide can regulate intestinal dysbiosis induced by a high-fat diet, which could be an underlying mechanism for its beneficial effects on cognitive function and inflammation in obese mice. The marked increase in the abundance of Akkermansia muciniphila after treatment with semaglutide is particularly notable, given the beneficial effects of this bacterium on metabolic and cognitive health. However, the authors note that further research is needed to confirm these results, in particular by exploring the effects of semaglutide on the human gut microbiota and its link with cognition and inflammation in clinical studies.
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