Abstract
Mannose is an important monosaccharide for protein glycosylation in mammals but is an inefficient cellular energy source. Using a C57BL6/J mouse model of diet-induced obesity, we show that mannose supplementation of high-fat-diet-fed mice prevents weight gain, lowers adiposity, reduces liver steatosis, increases endurance and maximal O2 consumption, and improves glucose tolerance. Mannose-supplemented mice have higher fecal energy content, suggesting reduced caloric absorption by the host. Mannose increases the Bacteroidetes to Firmicutes ratio in the gut microbiota, a signature associated with the lean phenotype. These beneficial effects of mannose are observed when supplementation is started early in life. Functional transcriptomic analysis of cecal microbiota revealed profound and coherent changes in microbial energy metabolism induced by mannose that are predicted to lead to reduced energy harvest from complex carbohydrates by gut microbiota. Our results suggest that the gut microbiota contributes to mannose-induced resistance to deleterious effects of a high-fat diet. VIDEO ABSTRACT.