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 (Aristotelia chilensis) 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, 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.