Divergent pathways of mango fractions in promoting metabolic health: from gut microbiota remodeling to direct systemic regulation

To dissect the distinct metabolic regulatory mechanisms of mango pulp (MPP), peel (MPL), and kernel (MKE), this study integrated 16S rRNA sequencing and fecal metabolomics in a mouse model. We uncovered a clear bifurcation in their actions. MPP and MPL acted primarily by remodeling the gut microbiota. Specifically, MPP treatment enriched Bilophila, while MPL treatment enriched Staphylococcus. Both components altered fecal peptide and lipid metabolism. In contrast, MKE displayed a direct systemic action largely independent of colonic microbial fermentation independent of the microbiota. Despite minimal impact on the fecal metabolome, its bioactive saponins were linked to the modulation of host steroid hormone biosynthesis, suggesting direct absorption. These findings establish a dual-mechanism model for mango’s bioactivity, providing a scientific framework for developing its components—specifically the MPP and MPL as microbiota-modulating agents and the MKE as a direct systemic regulator.