Bifidobacterium longum and microbiome maturation modify a nutrient intervention for stunting in Zimbabwean infants.

Margaret Kosek, Robert Ntozini, Bernard Chasekwa, Batsirai Mutasa, Andrew J Prendergast, Ruairi C Robertson, Mduduzi N N Mbuya, Naume Tavengwa, Amee R Manges, Ceri Evans, Florence D Majo, Kuda Mutasa, Thaddeus J Edens, Hyun Min Geum, Ethan K Gough, Lynnea Carr, Freddy Francis, Sandeep K Gill, Iman Baharmand, Joice Tome

Journal: EBioMedicine 2024;108():105362

PMID: 39341154

Free Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Department of International Health, Johns Hopkins Bloomberg School of Public Health; Baltimore, MD, USA. Electronic address: [email protected].; Devil's Staircase Consulting, West Vancouver, BC, Canada.; Department of Microbiology and Immunology, University of British Columbia; Vancouver, BC, Canada.; Blizard Institute, Queen Mary University of London, London, UK.; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Global Alliance for Improved Nutrition, Washington, DC, 20036, USA.; Department of Experimental Medicine, University of British Columbia, Vancouver, BC, Canada.; 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.; University of Virginia School of Medicine, Charlottesville, VA, USA.; Blizard Institute, Queen Mary University of London, London, UK; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada.

DOI: 10.1016/j.ebiom.2024.105362

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MeSH Terms: Humans, Infant, Gastrointestinal Microbiome, Growth Disorders, Female, Male, Zimbabwe, Fucosyltransferases, Feces, Bifidobacterium, Dietary Supplements, Nutrients