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Journal Articles Nature Year : 2023

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

Daniel Webber
Suzanne Henrissat
  • Function : Author
Hannah Lynn
Evan Lee
  • Function : Author
Janaki Lelwala-Guruge
  • Function : Author
Marat Kazanov
  • Function : Author
Semen Leyn
  • Function : Author
Vincent Lombard
  • Function : Author
Juan Castillo
Garret Couture
  • Function : Author
Nikita Bacalzo
Ye Chen
Carlito Lebrilla
Ishita Mostafa
  • Function : Author
Subhasish Das
  • Function : Author
Mustafa Mahfuz
  • Function : Author
Michael Barratt
  • Function : Author
Andrei Osterman
Tahmeed Ahmed
  • Function : Author
Jeffrey Gordon


Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition 1–4 . 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 malnutrition 4 . 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.


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hal-04472779 , version 1 (16-05-2024)




Matthew Hibberd, Daniel Webber, Dmitry Rodionov, Suzanne Henrissat, Robert Chen, et al.. Bioactive glycans in a microbiome-directed food for children with malnutrition. Nature, 2023, 625 (7993), pp.157-165. ⟨10.1038/s41586-023-06838-3⟩. ⟨hal-04472779⟩
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