6-Gingerol, an active ingredient of ginger, reshapes gut microbiota and serum metabolites in HFD-induced obese mice

6-Gingerol (6G), a bioactive compound derived from ginger, has shown promise in combating obesity. However, the specific anti-obesity action of 6G by targeting gut microbiota and serum metabolites remains unclear. Here, we showed that 6G positively and significantly modified the composition of gut microbiota by increasing the abundance of weight loss-associated genera (e.g., Muribaculaceae, Alloprevotella, and Akkermansiaand) and decreasing the abundance of obesity-contributed bacterium (e.g., Lachnospiraceae and Lactobacillus reuteri). Moreover, 6G remarkably altered serum metabolites related to lipid metabolism (e.g.,3a,7a-Dihydroxy-5b-cholestan-26-al, LysoPC(18:1(11Z)), LysoPC (20:0), Sphingosine-1-phosphate, and Adrenic acid) and their signaling pathways including ABC transporters, arginine biosynthesis, and arginine and proline metabolism. Spearman's correlation showed a strong connection between the altered microbiota and changes in serum lipid metabolites. Fecal microbiota transplantation revealed that Muribaculaceae, Alloprevotella, and Akkermansia, were the key microbiomes of the 6G intervention. This study provides valuable insights into the underlying mechanisms by which 6G promotes weight loss.