Modulation of the gut microbiome-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 (<i>Aristotelia chilensis)</i> supplementation on the gut microbiome-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 microbiome-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, <i>n</i> = 15) or HFD + Maqui (<i>n</i> = 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 <i>Lactobacillus, Lactococcus</i> and <i>Bifidobacterum</i> and a reduction in <i>Desulfovibrium,</i> and <i>Acetatifactor</i>. Out of 19 metabolites altered by maqui supplementation, 9 were derived from gut bacterial fermentation of anthocyanins. Increases in L. <i>gasseri</i> and L. <i>johnsonii</i> in the gut were associated to increased production of phenyllactic acid, 4-<i>O</i>-methylgallic acid, and 3-(3'-hydroxyphenyl)-γ-valerolactone. Integrative analysis revealed a concerted role of <i>Lactobacillus</i> spp. and its ability to ferment maqui polyphenols, along with increased expression of <i>Chrebpb</i>, <i>Pgc1a</i> and <i>Ucp1</i> in WAT. Enrichment of <i>Lactobacillus gasseri</i> and <i>johnsonii</i> 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.