RT Journal Article
SR Electronic
T1 Human milk oligosaccharide 2’-fucosyllactose protects against high-fat diet-induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and faecal proteome profiles in mice
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1632
OP 1649
DO 10.1136/gutjnl-2023-330301
VO 73
IS 10
A1 Paone, Paola
A1 Latousakis, Dimitris
A1 Terrasi, Romano
A1 Vertommen, Didier
A1 Jian, Ching
A1 Borlandelli, Valentina
A1 Suriano, Francesco
A1 Johansson, Malin E V
A1 Puel, Anthony
A1 Bouzin, Caroline
A1 Delzenne, Nathalie M
A1 Salonen, Anne
A1 Juge, Nathalie
A1 Florea, Bogdan I
A1 Muccioli, Giulio G
A1 Overkleeft, Herman
A1 Van Hul, Matthias
A1 Cani, Patrice D
YR 2024
UL http://gut.bmj.com/content/73/10/1632.abstract
AB Objective To decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2’-fucosyllactose (2’FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We wanted to elucidate whether 2’FL metabolic effects are linked with changes in intestinal mucus production and secretion, mucin glycosylation and degradation, as well as with the modulation of the gut microbiota, faecal proteome and endocannabinoid (eCB) system.Results 2’FL supplementation reduced HFD-induced obesity and glucose intolerance. These effects were accompanied by several changes in the intestinal mucus layer, including mucus production and composition, and gene expression of secreted and transmembrane mucins, glycosyltransferases and genes involved in mucus secretion. In addition, 2’FL increased bacterial glycosyl hydrolases involved in mucin glycan degradation. These changes were linked to a significant increase and predominance of bacterial genera Akkermansia and Bacteroides, different faecal proteome profile (with an upregulation of proteins involved in carbon, amino acids and fat metabolism and a downregulation of proteins involved in protein digestion and absorption) and, finally, to changes in the eCB system. We also investigated faecal proteomes from lean and obese humans and found similar changes observed comparing lean and obese mice.Conclusion Our results show that the HMO 2’FL influences host metabolism by modulating the mucus layer, gut microbiota and eCB system and propose the mucus layer as a new potential target for the prevention of obesity and related disorders.All data relevant to the study are included in the article or uploaded as online supplemental information. All data generated or analysed during this study are included in this published article and its online supplemental information files. The raw amplicon sequencing data analysed in this study have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI under accession number PRJEB72192. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [62] partner repository with the dataset identifier PXD049406.