A microbiome-directed therapeutic food for children recovering from severe acute malnutrition

Globally, severe acute malnutrition (SAM), defined as a weight-for-length <i>z</i>-score more than three SDs below a reference mean (WLZ < -3), affects 14 million children under 5 years of age. Complete anthropometric recovery after standard, short-term interventions is rare, with children often left with moderate acute malnutrition (MAM; WLZ -2 to -3). We conducted a randomized controlled trial (RCT) involving 12- to 18-month-old Bangladeshi children from urban and rural sites, who, after initial hospital-based treatment for SAM, received a 3-month intervention with a microbiome-directed complementary food (MDCF-2) or a calorically more dense, standard ready-to-use supplementary food (RUSF). The rate of WLZ improvement was significantly greater in MDCF-2-treated children (<i>P</i> = 8.73 × 10<sup>-3</sup>), similar to our previous RCT of Bangladeshi children with MAM without antecedent SAM (<i>P</i> = 0.032). A correlated meta-analysis of plasma levels of 4520 proteins in both RCTs revealed 215 positively associated with WLZ (largely representing musculoskeletal and central nervous system development) and 44 negatively associated (primarily related to immune activation). Moreover, the positively associated proteins were significantly enriched by MDCF-2 (<i>q</i> = 1.1 × 10<sup>-6</sup>). Characterizing the abundances of 754 bacterial metagenome-assembled genomes in serially collected fecal samples disclosed the effects of acute rehabilitation for SAM on the microbiome and how, during treatment for MAM, specific strains of <i>Prevotella copri</i> function at the intersection between MDCF-2 glycan metabolism and anthropometric recovery. These results provide a rationale for further testing the generalizability of MDCF efficacy and for identifying biomarkers to define treatment responses.

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Publication Details

Journal
Science Translational Medicine
Published
2024-10-02
DOI
https://doi.org/10.1126/scitranslmed.adn2366
Citations
15
Primary Topic
Child Nutrition and Feeding Issues
Type
article
Field-Weighted Citation Impact
5.78

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article

A microbiome-directed therapeutic food for children recovering from severe acute malnutrition

Martin L. Hibberd, Michael A. Province, Nurun Nahar Naila, Andrei L. Osterman et al.
15 citations
Science Translational Medicine
Child Nutrition and Feeding Issues
5.78
article

A microbiome-directed therapeutic food for children recovering from severe acute malnutrition

Martin L. Hibberd, Michael A. Province, Nurun Nahar Naila, Andrei L. Osterman, Sayeeda Huq, Robert Y. Chen, Ishita Mostafa, Michael J. Barratt, Dmitry A. Rodionov, Nicolas Terrapon, Mustafa Mahfuz, Mahabub Uz Zaman, Bernard Henrissat, Jeffrey I. Gordon, Kallol Mukherji, Daniel M. Webber, Steven J. Hartman, Tahmeed Ahmed, Vaha Akbary Moghaddam, Suzanne Henrissat, Md. Tazul Islam, Md Munirul Islam
article en
15 citations

Abstract

Globally, severe acute malnutrition (SAM), defined as a weight-for-length <i>z</i>-score more than three SDs below a reference mean (WLZ < -3), affects 14 million children under 5 years of age. Complete anthropometric recovery after standard, short-term interventions is rare, with children often left with moderate acute malnutrition (MAM; WLZ -2 to -3). We conducted a randomized controlled trial (RCT) involving 12- to 18-month-old Bangladeshi children from urban and rural sites, who, after initial hospital-based treatment for SAM, received a 3-month intervention with a microbiome-directed complementary food (MDCF-2) or a calorically more dense, standard ready-to-use supplementary food (RUSF). The rate of WLZ improvement was significantly greater in MDCF-2-treated children (<i>P</i> = 8.73 × 10<sup>-3</sup>), similar to our previous RCT of Bangladeshi children with MAM without antecedent SAM (<i>P</i> = 0.032). A correlated meta-analysis of plasma levels of 4520 proteins in both RCTs revealed 215 positively associated with WLZ (largely representing musculoskeletal and central nervous system development) and 44 negatively associated (primarily related to immune activation). Moreover, the positively associated proteins were significantly enriched by MDCF-2 (<i>q</i> = 1.1 × 10<sup>-6</sup>). Characterizing the abundances of 754 bacterial metagenome-assembled genomes in serially collected fecal samples disclosed the effects of acute rehabilitation for SAM on the microbiome and how, during treatment for MAM, specific strains of <i>Prevotella copri</i> function at the intersection between MDCF-2 glycan metabolism and anthropometric recovery. These results provide a rationale for further testing the generalizability of MDCF efficacy and for identifying biomarkers to define treatment responses.

Science Translational MedicineVol. 16(767)
Centre National de la Recherche Scientifique (FR), Sanford Burnham Prebys Medical Discovery Institute (US), Washington University in St. Louis (US), International Centre for Diarrhoeal Disease Research (BD), Aix-Marseille Université (FR), Discovery Institute (US), Architecture et Fonction des Macromolécules Biologiques (FR), Technical University of Denmark (DK)
Bill and Melinda Gates Foundation, Centene Corporation, International Centre for Diarrhoeal Disease Research, Bangladesh, National Institutes of Health
Zero hunger
Openalex Percentile: Top 3%
Child Nutrition and Feeding Issues
5.78
DOIOpen Access PDFOpenAlex
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