Molecular networking-based lipid profiling and multi-omics approaches reveal new contributions of functional vanilloids to gut microbiota and lipometabolism changes

• Vanilloids from Grains of Paradise (GOP) exhibited anti-obesity effects. • Molecular mechanism investigated using multi-omics approaches. • GOP extract and its vanilloids restored unbalanced gut microbiota in HFD mice. • GOP extract and its vanilloids improved F/B ratio and increased Bifidobacterium levels. • GOP extract improved fecal lipid content. Obesity is now recognized as an epidemic, requiring rapid intervention. We previously demonstrated that vanilloids from the African spice known as Grains of Paradise (GOP) exhibit strong anti-obesity effects. Here, the molecular mechanism behind the obesity prevention property of the GOP extract was investigated by employing molecular networking-based lipid profiling and 16S rRNA sequencing. Administration of either GOP extract or two of its components, 6-paradol and 6-gingerol, reversed the unbalanced gut microbiota composition induced by a high-fat diet (HFD) with a decrease in Firmicutes / Bacteroidetes ratio and increase in genera Bifidobacterium and Akkermansia . Moreover, GOP extract ameliorated abnormal fatty acid metabolism in gut bacteria. Furthermore, lipid molecular networking revealed differences in lipid composition, such as triglycerides and bile acids, in the feces. These results suggest that 6-paradol and 6-gingerol can restore an unhealthy gut environment and prevent lipid absorption, a possible consequence of the reconstruction of the gut microbiota.