Modulation of the gut microbiota-adipose tissue AXIS by maqui supplementation improved insulin resistance and lipid metabolism in mice under a high-fat diet

To assess the impact of maqui ( Aristotelia chilensis) supplementation on the gut microbiota-adipose tissue axis, and to associate it with gene expression changes in white adipose tissue (WAT) in mice fed a high-fat diet. Our hypothesis is that the gut microbiota-adipose tissue axis will be involved in Maqui's effect on WAT browning. Twenty-nine 4-week-old C57BL/6 J mice were randomly assigned to a high-fat diet (HFD, n = 15) or HFD + Maqui ( n = 14) for 16 weeks. Plasma samples were analyzed using an UPLC-QTRAP exposome-based metabolomics method. Gut microbiome was studied by fecal 16S rRNA gene sequencing. Gene expression in WAT was assessed by real-time PCR. Data were analyzed by multivariate methods and integrated through multiomics analyses. Maqui supplementation induced an increase in Lactobacillus, Lactococcus and Bifidobacterum and a reduction in Desulfovibrium, and Acetatifactor . Out of 19 metabolites altered by maqui supplementation, 9 were derived from gut bacterial fermentation of anthocyanins. Increases in L. gasseri and L. johnsonii in the gut were associated to increased production of phenyllactic acid, 4- O -methylgallic acid, and 3-(3′-hydroxyphenyl)-γ-valerolactone. Integrative analysis revealed a concerted role of Lactobacillus spp. and its ability to ferment maqui polyphenols, along with increased expression of Chrebpb , Pgc1a and Ucp1 in WAT. Enrichment of Lactobacillus gasseri and johnsonii and exposure to 2-hydroxybenzoic acid derived from polyphenols fermentation are evidences of the involvment of the gut-microbiome-adipose tissue axis in WAT browning induced by maqui. • WAT browning after maqui supplementation prevented weight gain and glucose metabolism alterations. • Maqui supplementation reshaped the gut microbiota composition. • Benzoic acids and phenyl-γ-valerolactones were increased after maqui supplementation. • Browning markers in WAT were associated with changes in gut microbiota and plasma metabolomics • Maqui may prevent obesity in HFD-male mice by modulating the gut microbiota-adipose tissue axis.