Bioactive glycans in a microbiome-directed food for children with malnutrition

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition. 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 malnutrition. 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.

Matthew C. Hibberd, Daniel M. Webber, Dmitry A. Rodionov, Suzanne Henrissat, Robert Y. Chen, Cyrus Zhou, Hannah M. Lynn, Yi Wang, Hao-Wei Chang, Evan M. Lee, Janaki Lelwala-Guruge, Marat D. Kazanov, Aleksandr A. Arzamasov, Semen A. Leyn, Vincent Lombard, Nicolas Terrapon, Bernard Henrissat, Juan J. Castillo, Garret Couture, Nikita P. Bacalzo Jr, Ye Chen, Carlito B. Lebrilla, Ishita Mostafa, Subhasish Das, Mustafa Mahfuz, Michael J. Barratt, Andrei L. Osterman, Tahmeed Ahmed, Jeffrey I. Gordon