Butyrate producing colonic Clostridiales metabolise human milk oligosaccharides and cross feed on mucin via conserved pathways
Butyrate producing colonic Clostridiales metabolise human milk oligosaccharides and cross feed on mucin via conserved pathways
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DOI：
10.1038/s41467-020-17075-x
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发表时间：
2020-07-03
影响因子：
16.6
通讯作者：
Abou Hachem, Maher
中科院分区：
文献类型：
--
作者：
Pichler, Michael Jakob;Yamada, Chihaya;Abou Hachem, Maher
早期人类肠道微生物群对宿主产生终身健康影响，但其组装的机制仍然难以捉摸。特别地，与保护免受结直肠癌、免疫和代谢紊乱相关的来自罗斯拜瑞氏菌-真杆菌组的梭菌目的早期定殖是谜。在这里，我们描述的分解代谢途径，支持罗斯拜瑞氏菌属和真杆菌属成员对不同的人乳低聚糖（HMO）的增长。HMO途径包括具有先前未知结构折叠和特异性的酶，在选定的HMO上生长期间以及与嗜粘蛋白阿克曼氏菌在粘蛋白上共培养期间，HMO途径与其他聚糖利用位点一起上调，这表明HMO途径在实现交叉方面发挥了额外的作用喂养和获得粘蛋白O-聚糖。4599 Roseburia基因组的分析强调了优势和多样性的HMO利用位点的属内。产丁酸梭菌对HMO的催化作用可能有助于在断奶触发的微生物群成熟过程中这一群体的竞争力。生命早期微生物组的组装和成熟对人类健康具有终身影响。在这里，作者结合了联合收割机组学、功能测定和结构分析，以表征支持罗斯拜瑞氏菌属和真杆菌属产丁酸梭菌目成员在不同人乳寡糖上生长的分解代谢途径。
The early life human gut microbiota exerts life-long health effects on the host, but the mechanisms underpinning its assembly remain elusive. Particularly, the early colonization of Clostridiales from the Roseburia-Eubacterium group, associated with protection from colorectal cancer, immune- and metabolic disorders is enigmatic. Here, we describe catabolic pathways that support the growth of Roseburia and Eubacterium members on distinct human milk oligosaccharides (HMOs). The HMO pathways, which include enzymes with a previously unknown structural fold and specificity, were upregulated together with additional glycan-utilization loci during growth on selected HMOs and in co-cultures with Akkermansia muciniphila on mucin, suggesting an additional role in enabling cross-feeding and access to mucin O-glycans. Analyses of 4599 Roseburia genomes underscored the preponderance and diversity of the HMO utilization loci within the genus. The catabolism of HMOs by butyrate-producing Clostridiales may contribute to the competitiveness of this group during the weaning-triggered maturation of the microbiota. The assembly and maturation of the early life microbiome has life-long effects on human health. Here, the authors combine omics, functional assays and structural analyses to characterize the catabolic pathways that support the growth of butyrate producing Clostridiales members from the Roseburia and Eubacterium, on distinct human milk oligosaccharides.