2. Academic Validation
  3. Bioactive glycans in a microbiome-directed food for children with malnutrition

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

  • Nature. 2024 Jan;625(7993):157-165. doi: 10.1038/s41586-023-06838-3.
Matthew C Hibberd # 1 2 3,  Daniel M Webber # 1 2 3,  Dmitry A Rodionov 4,  Suzanne Henrissat 1 2 5,  Robert Y Chen 1 2,  Cyrus Zhou 1 2,  Hannah M Lynn 1 2,  Yi Wang 1 2,  Hao-Wei Chang 1 2,  Evan M Lee 1 2,  Janaki Lelwala-Guruge 1 2,  Marat D Kazanov 6,  Aleksandr A Arzamasov 4,  Semen A Leyn 4,  Vincent Lombard 5,  Nicolas Terrapon 5,  Bernard Henrissat 7 8,  Juan J Castillo 9,  Garret Couture 9,  Nikita P Bacalzo Jr 9,  Ye Chen 1 2 9,  Carlito B Lebrilla 9,  Ishita Mostafa 10,  Subhasish Das 10,  Mustafa Mahfuz 10,  Michael J Barratt 1 2 3,  Andrei L Osterman 4,  Tahmeed Ahmed 10,  Jeffrey I Gordon 11 12 13
Affiliations

Affiliations

  • 1 Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA.
  • 2 Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St Louis, MO, USA.
  • 3 Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
  • 4 Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
  • 5 Architecture et Fonction des Macromolécules Biologiques, CNRS, Aix-Marseille University, Marseille, France.
  • 6 Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.
  • 7 Department of Biotechnology and Biomedicine (DTU Bioengineering), Technical University of Denmark, Lyngby, Denmark.
  • 8 Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
  • 9 Department of Chemistry, University of California, Davis, Davis, CA, USA.
  • 10 International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
  • 11 Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA. jgordon@wustl.edu.
  • 12 Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St Louis, MO, USA. jgordon@wustl.edu.
  • 13 Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA. jgordon@wustl.edu.
  • # Contributed equally.
PMID: 38093016 DOI: 10.1038/s41586-023-06838-3
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.

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