A microbiota-directed complementary food intervention improves stunting in undernourished Bangladeshi children

Background Forty-five percent of deaths among children under 5-years-old have been linked to undernutrition. Stunting affects ~150 million children while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating the long-term sequelae of undernutrition which include stunting, cognitive deficits and immune dysfunction. Disruption in postnatal development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing a potential new therapeutic approach. Methods 124 Bangladeshi children with moderate acute malnutrition (MAM) enrolled at 12-18-months-of-age in a previously reported 3-month RCT of a microbiota-directed complementary food (MDCF-2) designed to repair their impaired microbial community development, were followed at 6-month intervals for two years after the intervention (n=107 completed follow-up). Growth was monitored with anthropometry, the abundances of bacterial strains were assessed by quantifying metagenome-assembled genomes (MAGs) in serially collected fecal samples, and physiologic responses were ascertained by quantifying levels of plasma protein biomarkers of a variety of growth-associated processes. Findings In addition to superior ponderal growth during treatment, children who received MDCF-2 were significantly less stunted (defined by length-for-age Z score; LAZ) in the 2-year follow-up period than children who had been treated with a standard ready-to-use supplementary food (RUSF) [linear mixed effects model, P=0.005]. The superior anthropometric responses to MDCF-2 were associated with differences in MAG composition, and significantly increased levels of a group of 38 plasma proteins (linear model; q<0.1) linked to musculoskeletal accretion and CNS development that persisted for 6-months after cessation of intervention. Interpretation A 3-month intervention with MDCF-2 in Bangladeshi children with MAM produced sustained improvements in their ponderal growth and stunting compared to a standard RUSF. These data provide evidence that next-generation treatments for undernutrition should not only include macro-/micronutrients directly utilized by the host, but also include ingredients that sponsor healthy microbiota-host co-development.