2'FL and gut microbiota in mice

Objective To decipher the mechanisms by which the major human milk oligosaccharide (HMOs) 2'-fucosyllactose (2'FL) can affect body weight and fat mass gain upon high-fat diet (HFD) feeding. To elucidate whether 2'FL metabolic effects are linked with changes in intestinal mucus layer production, glycosylation, secretion and degradation, as well as to the modulation of the gut microbiota, fecal proteome and endocannabinoid (eCB) system. Results 2'FL supplementation reduced HFD-induced obesity and glucose intolerance together with several changes in the mucus layer. In particular, 2'FL increased mucus production, expression of secreted and transmembrane mucins, glycosyltransferases and genes involved in mucus secretion. 2'FL changed mucus composition and increased bacterial glycosyl hydrolases (GHs) involved in mucus degradation. These changes were linked to significant increase and predominance of bacterial genera Akkermansia and Bacteroides, different fecal proteome, upregulating proteins involved in carbon and lipid metabolism and downregulating proteins involved proteolysis and, finally, to changes of the eCB system. Conclusion These results suggest that the HMO 2'FL influence host metabolism through changing the mucus layer, gut microbiota and eCB system and suggest that the mucus layer could be a new target for the prevention of obesity and related disorders.