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.

中文翻译：

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母乳寡糖 2'-岩藻糖基乳糖通过改变与小鼠肠道微生物群和粪便蛋白质组谱变化相关的肠道粘液产生、组成和降解来预防高脂肪饮食引起的肥胖


目的 破译主要母乳低聚糖（HMO）2'-岩藻糖基乳糖（2'FL）影响高脂饮食（HFD）喂养小鼠体重和脂肪量增加的机制。我们想要阐明 2'FL 代谢效应是否与肠道粘液产生和分泌、粘蛋白糖基化和降解的变化以及肠道微生物群、粪便蛋白质组和内源性大麻素 (eCB) 系统的调节有关。结果 2'FL 补充剂减少了 HFD 引起的肥胖和葡萄糖不耐受。这些影响伴随着肠道粘液层的一些变化，包括粘液的产生和组成、分泌和跨膜粘蛋白的基因表达、糖基转移酶和参与粘液分泌的基因。此外，2'FL 增加了参与粘蛋白聚糖降解的细菌糖基水解酶。这些变化与阿克曼氏菌属和拟杆菌属的显着增加和优势、不同的粪便蛋白质组谱（参与碳、氨基酸和脂肪代谢的蛋白质上调以及参与蛋白质消化和吸收的蛋白质下调）有关，最后是欧洲央行体系的变化。我们还研究了瘦人和肥胖人的粪便蛋白质组，发现比较瘦人和肥胖小鼠观察到类似的变化。结论 我们的结果表明，HMO 2'FL 通过调节粘液层、肠道微生物群和 eCB 系统影响宿主代谢，并提出粘液层作为预防肥胖和相关疾病的新潜在目标。与研究相关的所有数据都包含在文章中或作为在线补充信息上传。 本研究期间生成或分析的所有数据均包含在本发表的文章及其在线补充信息文件中。本研究中分析的原始扩增子测序数据已存入欧洲核苷酸档案馆 (ENA) 的 EMBL-EBI，登录号为 PRJEB72192。质谱蛋白质组学数据已通过 PRIDE [62] 合作伙伴存储库存入 ProteomeXchange 联盟，数据集标识符为 PXD049406。