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

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; Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial Team

doi:10.1016/j.ebiom.2024.105362

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

EBioMedicine. 2024 Oct:108:105362. doi: 10.1016/j.ebiom.2024.105362. Epub 2024 Sep 27.

Authors

Ethan K Gough¹, Thaddeus J Edens², Lynnea Carr³, Ruairi C Robertson⁴, Kuda Mutasa⁵, Robert Ntozini⁵, Bernard Chasekwa⁵, Hyun Min Geum⁶, Iman Baharmand⁶, Sandeep K Gill⁶, Batsirai Mutasa⁵, Mduduzi N N Mbuya⁷, Florence D Majo⁵, Naume Tavengwa⁵, Freddy Francis⁸, Joice Tome⁵, Ceri Evans⁹, Margaret Kosek¹⁰, Andrew J Prendergast¹¹, Amee R Manges¹²; Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial Team

Affiliations

¹ Department of International Health, Johns Hopkins Bloomberg School of Public Health; Baltimore, MD, USA. Electronic address: egough1@jh.edu.
² Devil's Staircase Consulting, West Vancouver, BC, Canada.
³ Department of Microbiology and Immunology, University of British Columbia; Vancouver, BC, Canada.
⁴ Blizard Institute, Queen Mary University of London, London, UK.
⁵ Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
⁶ School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
⁷ Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Global Alliance for Improved Nutrition, Washington, DC, 20036, USA.
⁸ Department of Experimental Medicine, University of British Columbia, Vancouver, BC, Canada.
⁹ 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.
¹⁰ University of Virginia School of Medicine, Charlottesville, VA, USA.
¹¹ Blizard Institute, Queen Mary University of London, London, UK; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
¹² School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada.

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.

Keywords: Infant; Metagenome; Microbiome; Nutrition; Stunting.

MeSH terms

Bifidobacterium
Dietary Supplements
Feces / microbiology
Female
Fucosyltransferases / genetics
Gastrointestinal Microbiome*
Growth Disorders* / microbiology
Growth Disorders* / prevention & control
Humans
Infant
Male
Nutrients
Zimbabwe

Substances

Fucosyltransferases