PT  - JOURNAL ARTICLE
AU  - Paone, Paola
AU  - Latousakis, Dimitris
AU  - Terrasi, Romano
AU  - Vertommen, Didier
AU  - Jian, Ching
AU  - Borlandelli, Valentina
AU  - Suriano, Francesco
AU  - Johansson, Malin E V
AU  - Puel, Anthony
AU  - Bouzin, Caroline
AU  - Delzenne, Nathalie M
AU  - Salonen, Anne
AU  - Juge, Nathalie
AU  - Florea, Bogdan I
AU  - Muccioli, Giulio G
AU  - Overkleeft, Herman
AU  - Van Hul, Matthias
AU  - Cani, Patrice D
TI  - 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
AID  - 10.1136/gutjnl-2023-330301
DP  - 2024 Oct 01
TA  - Gut
PG  - 1632--1649
VI  - 73
IP  - 10
4099  - http://gut.bmj.com/content/73/10/1632.short
4100  - http://gut.bmj.com/content/73/10/1632.full
SO  - Gut2024 Oct 01; 73
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.