학술논문
Bioactive glycans in a microbiome-directed food for children with malnutrition.
Document Type
article
Author
Hibberd, Matthew; Webber, Daniel; Rodionov, Dmitry; Henrissat, Suzanne; Chen, Robert; Zhou, Cyrus; Lynn, Hannah; Wang, Yi; Chang, Hao-Wei; Lee, Evan; Lelwala-Guruge, Janaki; Kazanov, Marat; Arzamasov, Aleksandr; Leyn, Semen; Lombard, Vincent; Terrapon, Nicolas; Henrissat, Bernard; Castillo, Juan; Couture, Garret; Bacalzo, Nikita; Chen, Ye; Lebrilla, Carlito; Mostafa, Ishita; Das, Subhasish; Mahfuz, Mustafa; Barratt, Michael; Osterman, Andrei; Ahmed, Tahmeed; Gordon, Jeffrey
Source
Nature: New biology. 625(7993)
Subject
Language
Abstract
Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Here we analyse biospecimens from a randomized, controlled trial of a microbiome-directed complementary food (MDCF-2) that produced superior rates of weight gain compared with a calorically more dense conventional ready-to-use supplementary food in 12-18-month-old Bangladeshi children with moderate acute malnutrition4. We reconstructed 1,000 bacterial genomes (metagenome-assembled genomes (MAGs)) from the faecal microbiomes of trial participants, identified 75 MAGs of which the abundances were positively associated with ponderal growth (change in weight-for-length Z score (WLZ)), characterized changes in MAG gene expression as a function of treatment type and WLZ response, and quantified carbohydrate structures in MDCF-2 and faeces. The results reveal that two Prevotella copri MAGs that are positively associated with WLZ are the principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilizing the component glycans of MDCF-2. The predicted specificities of carbohydrate-active enzymes expressed by their polysaccharide-utilization loci are correlated with (1) the in vitro growth of Bangladeshi P. copri strains, possessing varying degrees of polysaccharide-utilization loci and genomic conservation with these MAGs, in defined medium containing different purified glycans representative of those in MDCF-2, and (2) the levels of faecal carbohydrate structures in the trial participants. These associations suggest that identifying bioactive glycan structures in MDCFs metabolized by growth-associated bacterial taxa will help to guide recommendations about their use in children with acute malnutrition and enable the development of additional formulations.