A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth

Abstract

Background Globally, stunting affects ~150 million children under five, while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating long-term sequelae of undernutrition including stunting, cognitive deficits and immune dysfunction. Disrupted development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing potentially new treatment approaches. Methods 124 Bangladeshi children with moderate acute malnutrition (MAM) enrolled (at 12-18 months) in a previously reported 3-month RCT of a microbiota-directed complementary food (MDCF-2) were followed for two years. Weight and length were monitored by anthropometry, the abundances of bacterial strains were assessed by quantifying metagenome-assembled genomes (MAGs) in serially collected fecal samples and levels of growth-associated proteins were measured in plasma. Findings Children who had received MDCF-2 were significantly less stunted during follow-up than those who received a standard ready-to-use supplementary food (RUSF) [linear mixed-effects model, βtreatment group x study week (95% CI) = 0.002 (0.001, 0.003); P=0.004]. They also had elevated fecal abundances of Agathobacter faecis, Blautia massiliensis, Lachnospira and Dialister, plus increased levels of a group of 37 plasma proteins (linear model; FDR-adjusted P<0.1), including IGF-1, neurotrophin receptor NTRK2 and multiple proteins linked to musculoskeletal and CNS development, that persisted for 6-months post-intervention. Interpretation MDCF-2 treatment of Bangladeshi children with MAM, which produced significant improvements in wasting during intervention, also reduced stunting during follow-up. These results suggest that the effectiveness of supplementary foods for undernutrition may be improved by including ingredients that sponsor healthy microbiota-host co-development.

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

“…In both studies, though wasting was frequently accompanied by stunting, MDCF-2 did not produce a statistically significant effect on LAZ compared to RUSF during the 3-month intervention period. However, MDCF-2 led to a significant improvement in linear growth trajectories of children with primary MAM in the subsequent 2-year period of follow-up ( 8 ); this effect was foreshadowed by increased levels of plasma proteomic biomarkers and mediators of musculoskeletal development at the end of the treatment phase. Longer periods of intervention and/or more extended post-treatment follow-up will be needed to determine whether stunting, and/or neurodevelopmental abnormalities, are ameliorated by MDCF-2 in children with post-SAM MAM.…”

“…MDCF-2 contained four complementary food components (chickpea flour, soybean flour, peanut paste, green banana) plus soybean oil, sugar and micronutrients ( 3, 7 ). The superior effect of MDCF-2 on β-WLZ was accompanied by more complete microbiota repair plus greater increases in levels of plasma protein mediators and biomarkers of musculoskeletal and central nervous system (CNS) development at the end of treatment ( 7 ) and a significant improvement in linear growth trajectories in the 2-year period after cessation of treatment ( 8 ). Shotgun sequencing of DNA isolated from fecal biospecimens serially collected during this trial identified 75 bacterial metagenome assembled genomes (MAGs) whose abundances were significantly positively associated with WLZ and whose genomes were enriched for metabolic pathways involved in utilization of plant polysaccharides ( 9 ).…”