Bifidobacterium longum and microbiome maturation modify a nutrient intervention for stunting in Zimbabwean infantsResearch in context
Ethan K. Gough,
Thaddeus J. Edens,
Lynnea Carr,
Ruairi C. Robertson,
Kuda Mutasa,
Robert Ntozini,
Bernard Chasekwa,
Hyun Min Geum,
Iman Baharmand,
Sandeep K. Gill,
Batsirai Mutasa,
Mduduzi N.N. Mbuya,
Florence D. Majo,
Naume Tavengwa,
Freddy Francis,
Joice Tome,
Ceri Evans,
Margaret Kosek,
Andrew J. Prendergast,
Amee R. Manges
Affiliations
Ethan K. Gough
Department of International Health, Johns Hopkins Bloomberg School of Public Health; Baltimore, MD, USA; Corresponding author.
Thaddeus J. Edens
Devil's Staircase Consulting, West Vancouver, BC, Canada
Lynnea Carr
Department of Microbiology and Immunology, University of British Columbia; Vancouver, BC, Canada
Ruairi C. Robertson
Blizard Institute, Queen Mary University of London, London, UK
Kuda Mutasa
Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Robert Ntozini
Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Bernard Chasekwa
Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Hyun Min Geum
School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
Iman Baharmand
School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
Sandeep K. Gill
School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
Batsirai Mutasa
Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Mduduzi N.N. Mbuya
Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Global Alliance for Improved Nutrition, Washington, DC, 20036, USA
Florence D. Majo
Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Naume Tavengwa
Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Freddy Francis
Department of Experimental Medicine, University of British Columbia, Vancouver, BC, Canada
Joice Tome
Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Ceri Evans
Blizard Institute, Queen Mary University of London, London, UK; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, UK
Margaret Kosek
University of Virginia School of Medicine, Charlottesville, VA, USA
Andrew J. Prendergast
Blizard Institute, Queen Mary University of London, London, UK; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Amee R. Manges
School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada
Summary: Background: Small-quantity lipid-based nutrient supplements (SQ-LNS), which has been widely tested to reduce child stunting, has largely modest effects to date, but the mechanisms underlying these modest effects are unclear. Child stunting is a longstanding indicator of chronic undernutrition and it remains a prevalent public health problem. The infant gut microbiome may be a key contributor to stunting; and mother and infant fucosyltransferase (FUT) phenotypes are important determinants of infant microbiome composition. Methods: We investigated whether mother-infant FUT status (n = 792) and infant gut microbiome composition (n = 354 fecal specimens from 172 infants) modified the impact of an infant and young child feeding (IYCF) intervention, that included SQ-LNS, on stunting at age 18 months in secondary analysis of a randomized trial in rural Zimbabwe. Findings: We found that the impact of the IYCF intervention on stunting was modified by: (i) mother-infant FUT2+/FUT3− phenotype (difference-in-differences −32.6% [95% CI: −55.3%, −9.9%]); (ii) changes in species composition that reflected microbiome maturation (difference-in-differences −68.1% [95% CI: −99.0%, −28.5%); and (iii) greater relative abundance of B. longum (differences-in-differences 49.1% [95% CI: 26.6%, 73.6%]). The dominant strains of B. longum when the intervention started were most similar to the proficient milk oligosaccharide utilizer subspecies infantis, which decreased with infant age and differed by mother-infant FUT2+/FUT3− phenotypes. Interpretation: These findings indicate that a persistently “younger” microbiome at initiation of the intervention reduced its benefits on stunting in areas with a high prevalence of growth restriction. Funding: Bill and Melinda Gates Foundation, UK DFID/Aid, Wellcome Trust, Swiss Agency for Development and Cooperation, US National Institutes of Health, UNICEF, and Nutricia Research Foundation.
