A microbiota-directed complementary food intervention in 12–18-month-old Bangladeshi children improves linear growthResearch in context
Ishita Mostafa,
Matthew C. Hibberd,
Steven J. Hartman,
Md Hasan Hafizur Rahman,
Mustafa Mahfuz,
S.M. Tafsir Hasan,
Per Ashorn,
Michael J. Barratt,
Tahmeed Ahmed,
Jeffrey I. Gordon
Affiliations
Ishita Mostafa
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, 1212, Bangladesh; Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland
Matthew C. Hibberd
Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA; The Newman Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO, 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA
Steven J. Hartman
Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA; The Newman Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO, 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA
Md Hasan Hafizur Rahman
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, 1212, Bangladesh
Mustafa Mahfuz
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, 1212, Bangladesh; Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland
S.M. Tafsir Hasan
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, 1212, Bangladesh
Per Ashorn
Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland
Michael J. Barratt
Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA; The Newman Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO, 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA
Tahmeed Ahmed
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, 1212, Bangladesh
Jeffrey I. Gordon
Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA; The Newman Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO, 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA; Corresponding author. The Edison Family Center for Genome Sciences and Systems Biology, 4515 McKinley Ave, St. Louis, MO, 63110, USA.
Summary: 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. Funding: This work was supported by the BMGF (Grants OPP1134649/INV-000247).
