TY - JOUR

T1 - Butyrate producing colonic Clostridiales metabolise human milk oligosaccharides and cross feed on mucin via conserved pathways

AU - Pichler, Michael Jakob

AU - Yamada, Chihaya

AU - Shuoker, Bashar

AU - Alvarez-Silva, Camila

AU - Gotoh, Aina

AU - Leth, Maria Louise

AU - Schoof, Erwin

AU - Katoh, Toshihiko

AU - Sakanaka, Mikiyasu

AU - Katayama, Takane

AU - Jin, Chunsheng

AU - Karlsson, Niclas G.

AU - Arumugam, Manimozhiyan

AU - Fushinobu, Shinya

AU - Abou Hachem, Maher

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - HUMAN GUT MICROBIOME

KW - BLOOD-GROUP-A

KW - BACTERIAL DIVERSITY

KW - PROTEIN-SEQUENCE

KW - BREAST-MILK

KW - GEN. NOV.

KW - BIFIDOBACTERIUM

KW - HEALTH

KW - PURIFICATION

KW - DYNAMICS

U2 - 10.1038/s41467-020-17075-x

DO - 10.1038/s41467-020-17075-x

M3 - Journal article

C2 - 32620774

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 3285

ER -