Lactobacillus casei Zhang exerts anti-obesity effect to obese glut1 and gut-specific-glut1 knockout mice via gut microbiota modulation mediated different metagenomic pathways

Obesity is a major risk factor for various metabolic diseases, including metabolic syndrome and type-2 diabetes. Glucose transporter 1 (GLUT1) impairment has been proposed as a mechanism of fat accumulation and glucose tolerance. Our aims were to determine the role of intestinal epithelial glut1 activity in obesity and the mechanism of anti-obesity effect of Lactobacillus casei Zhang (LCZ) intervention in the absence of gut villi-specific glut1 expression.This study compared the body weight, intestinal microbiota perturbations, fat mass accumulation, and glucose tolerance (by oral glucose tolerance test) between high-fat diet fed villi-specific glut1 knockout (KO) mice and control mice (glut1 flox/flox) with/without LCZ intervention. The intestinal microbiota was evaluated by metagenomic sequencing.Our results showed that villi-specific glut1 KO mice had more fat deposition at the premetaphase stage, impaired glucose tolerance, and obvious alterations in gut microbiota compared to control mice. Probiotic administration significantly lowered the body weight, the weights of mesenteric and perirenal white adipose tissues (WAT), and mediated gut microbiota modulation in both types of KO and control mice. The species Barnesiella intestinihominis and Faecalibaculum rodentium might contribute to fasting fat mass accumulation associated with gut-specific glut1 inactivation, while the probiotic-mediated anti-obesity effect was linked to members of the Bacteroides genera, Odoribacter genera and Alistipes finegoldii.Our study demonstrated that abrogating gut epithelial GLUT1 activity affected the gut microbiota, fat mass accumulation, and glucose tolerance; and LCZ administration reduced fat mass accumulation and central obesity.