• Robert Y Chen, Ishita Mostafa, Matthew C Hibberd, Subhasish Das, Mustafa Mahfuz, Nurun N Naila, M Munirul Islam, Sayeeda Huq, M Ashraful Alam, Mahabub U Zaman, Arjun S Raman, Daniel Webber, Cyrus Zhou, Vinaik Sundaresan, Kazi Ahsan, Martin F Meier, Michael J Barratt, Tahmeed Ahmed, and Jeffrey I Gordon.
• From the Edison Family Center for Genome Sciences and Systems Biology (R.Y.C., M.C.H., A.S.R., D.W., C.Z., V.S., K.A., M.F.M., M.J.B., J.I.G.), the Center for Gut Microbiome and Nutrition Research (R.Y.C., M.C.H., A.S.R., D.W., C.Z., V.S., K.A., M.F.M., M.J.B., J.I.G.), and the Department of Pathology and Immunology (M.C.H., A.S.R., D.W., M.J.B., J.I.G.), Washington University School of Medicine, St. Louis; and the International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (I.M., S.D., M.M., N.N.N., M.M.I., S.H., M.A.A., M.U.Z., T.A.).
• N. Engl. J. Med. 2021 Apr 22; 384 (16): 151715281517-1528.

BackgroundMore than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota.MethodsIn this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference values at baseline and every 2 weeks during the intervention period and at 4 months. We compared the rate of change of these related phenotypes between baseline and 3 months and between baseline and 4 months. We also measured levels of 4977 proteins in plasma and 209 bacterial taxa in fecal samples.ResultsA total of 118 children (59 in each study group) completed the intervention. The rates of change in the weight-for-length and weight-for-age z scores are consistent with a benefit of MDCF-2 on growth over the course of the study, including the 1-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 plasma proteins and of 21 associated bacterial taxa that were positively correlated with the weight-for-length z score (P<0.001 for comparisons of both protein and bacterial taxa). These proteins included mediators of bone growth and neurodevelopment.ConclusionsThese findings provide support for MDCF-2 as a dietary supplement for young children with moderate acute malnutrition and provide insight into mechanisms by which this targeted manipulation of microbiota components may be linked to growth. (Supported by the Bill and Melinda Gates Foundation and the National Institutes of Health; ClinicalTrials.gov number, NCT04015999.).Copyright © 2021 Massachusetts Medical Society.

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