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.

生命早期的人类肠道微生物群会对宿主产生终生健康影响，但支持其组装的机制仍然难以捉摸。特别是，来自Roseburia - Eubacterium组的梭状芽孢杆菌的早期定植与预防结直肠癌、免疫和代谢紊乱有关，这令人费解。在这里，我们描述了支持Roseburia和Eubacterium成员在不同的人乳低聚糖 (HMO) 上生长的分解代谢途径。HMO 途径，包括具有以前未知的结构折叠和特异性的酶，在选定的 HMO 生长期间以及与Akkermansia muciniphila的共培养过程中与其他聚糖利用位点一起被上调在粘蛋白上，表明在实现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 利用位点的优势和多样性。产丁酸盐梭菌目对 HMO 的分解代谢可能有助于该组在断奶触发的微生物群成熟过程中的竞争力。