Department of Biotechnology and Biomedicine, Technical University of Denmark, 2800, Lyngby, Denmark.
Department of Biotechnology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Nat Commun. 2020 Jul 3;11(1):3285. doi: 10.1038/s41467-020-17075-x.
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.
早期人类肠道微生物群对宿主的终生健康有影响，但支持其组装的机制仍难以捉摸。特别是与预防结直肠癌、免疫和代谢紊乱相关的 Roseburia-Eubacterium 群的 Clostridiales 的早期定植是神秘的。在这里，我们描述了支持 Roseburia 和 Eubacterium 成员在不同人乳寡糖（HMO）上生长的分解代谢途径。这些 HMO 途径包括具有以前未知结构折叠和特异性的酶，在选定的 HMO 上生长和与 Akkermansia muciniphila 在粘蛋白上共培养时，与其他聚糖利用基因座一起上调，表明在促进交叉喂养和获得粘蛋白 O-聚糖方面具有额外的作用。对 4599 个 Roseburia 基因组的分析强调了该属内 HMO 利用基因座的优势和多样性。产丁酸的 Clostridiales 对 HMO 的分解代谢可能有助于该群在微生物群引发的断奶成熟过程中的竞争力。
