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A microbiome-directed therapeutic food for children recovering from severe acute malnutrition
Insights
Microbiota-directed complementary food (MDCF-2) improved weight-for-length z-score (WLZ) more than ready-to-use supplementary food (RUSF) in children recovering from severe acute malnutrition (SAM). This intervention also altered plasma proteins and gut bacteria, aiding growth recovery.
Area of Science:
- Nutritional Science
- Microbiology
- Pediatrics
Background:
- Severe acute malnutrition (SAM) affects 19 million children globally, often resulting in incomplete recovery and moderate acute malnutrition (MAM).
- Standard interventions for SAM frequently leave children with MAM, highlighting a need for improved transitional feeding strategies.
- Understanding the interplay between nutrition, host physiology, and the gut microbiome is crucial for optimizing recovery from malnutrition.
Purpose of the Study:
- To compare the efficacy of a microbiota-directed complementary food (MDCF-2) versus ready-to-use supplementary food (RUSF) in improving anthropometric outcomes in children transitioning from SAM to MAM.
- To investigate the impact of these interventions on plasma protein profiles and the gut microbiome.
- To identify potential biomarkers associated with growth recovery in malnourished children.
Main Methods:
- A randomized controlled trial (RCT) involving 12-18-month-old Bangladeshi children treated for SAM.
- Children received either MDCF-2 or RUSF for 3 months during the transition to MAM.
- A meta-analysis of plasma proteins and characterization of fecal bacterial metagenomes were performed.
Main Results:
- MDCF-2 led to a significantly greater rate of weight-for-length z-score (WLZ) improvement compared to RUSF.
- 215 plasma proteins were positively associated with WLZ, with higher levels in the MDCF-2 arm, notably those linked to musculoskeletal and CNS development.
- Microbiome analysis revealed the effects of SAM rehabilitation and the transition to MAM, with specific Prevotella copri strains showing functional roles.
- 44 plasma proteins were negatively associated with WLZ, related to immune activation.
Conclusions:
- MDCF-2 demonstrates superior efficacy over RUSF in promoting anthropometric recovery in children transitioning from SAM to MAM.
- Specific plasma proteins and gut microbial changes are associated with improved growth outcomes, suggesting potential biomarkers for treatment response.
- These findings support further investigation into the generalizability and efficacy of MDCF interventions for childhood malnutrition.
Abstract:
Severe acute malnutrition (SAM), defined anthropometrically as a weight-for-length z-score more than 3 standard deviations below the mean (WLZ<-3), affects 19 million children under 5-years-old worldwide. Complete anthropometric recovery after standard inventions is rare with children often left with moderate acute malnutrition (MAM; WLZ -2 to -3). Here we conduct a randomized controlled trial (RCT), involving 12-18-month-old Bangladeshi children from urban and rural sites, who after hospital-based treatment for SAM received a 3-month intervention with a microbiota-directed complementary food (MDCF-2) or a ready-to-use supplementary food (RUSF) as they transitioned to MAM. The rate of WLZ improvement was significantly greater with MDCF-2 than the more calorically-dense RUSF, as we observed in a previous RCT of Bangladeshi children with MAM without antecedent SAM. A correlated meta-analysis of aptamer-based measurements of 4,520 plasma proteins in this and the prior RCT revealed 215 proteins positively-associated with WLZ (prominently those involved in musculoskeletal and CNS development) and 44 negatively-associated proteins (related to immune activation), with a significant enrichment in levels of the positively WLZ-associated proteins in the MDCF-2 arm. Characterizing changes in 754 bacterial metagenome-assembled genomes in serially collected fecal samples disclosed the effects of acute rehabilitation for SAM on the microbiome, its transition as each child achieves a state of MAM, and how specific strains of Prevotella copri function at the intersection between MDCF-2 glycan metabolism and the rescue of growth faltering. These results provide a rationale for further testing the generalizability of the efficacy of MDCF and identify biomarkers for defining treatment responses.
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