Maternal balanced energy-protein supplementation reshapes the maternal gut microbiome and enhances carbohydrate metabolism in infants: a randomized controlled trial

Lishi Deng, Steff Taelman, Matthew R. Olm, Laeticia Celine Toe, Eva Balini, Lionel Olivier Ouédraogo, Yuri Bastos-Moreira, Alemayehu Argaw, Kokeb Tesfamariam, Erica D. Sonnenburg, Giles T. Hanley-Cook, Moctar Ouédraogo, Rasmané Ganaba, Wim Criekinge, Lieven Huybregts, Michiel Stock, Patrick Kolsteren, Justin L. Sonnenburg, Carl Lachat () and Trenton Dailey-Chwalibóg ()
Additional contact information
Lishi Deng: Ghent University
Steff Taelman: Ghent University
Matthew R. Olm: Stanford University School of Medicine
Laeticia Celine Toe: Ghent University
Eva Balini: BioLizard nv
Lionel Olivier Ouédraogo: Ghent University
Yuri Bastos-Moreira: Ghent University
Alemayehu Argaw: Ghent University
Kokeb Tesfamariam: Ghent University
Erica D. Sonnenburg: Stanford University School of Medicine
Giles T. Hanley-Cook: Ghent University
Moctar Ouédraogo: Agence de Formation de Recherche et d’Expertise en Santé pour l’Afrique (AFRICSanté)
Rasmané Ganaba: Agence de Formation de Recherche et d’Expertise en Santé pour l’Afrique (AFRICSanté)
Wim Criekinge: Ghent University
Lieven Huybregts: Ghent University
Michiel Stock: Ghent University
Patrick Kolsteren: Ghent University
Justin L. Sonnenburg: Stanford University School of Medicine
Carl Lachat: Ghent University
Trenton Dailey-Chwalibóg: Ghent University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Balanced energy-protein (BEP) supplementation during pregnancy and lactation can improve birth outcomes and infant growth, with the gut microbiome as a potential mediator. The MISAME-III randomized controlled trial (ClinicalTrial.gov: NCT03533712) assessed the effect of BEP supplementation, provided during pregnancy and the first six months of lactation, on small-for-gestational age prevalence and length-for-age Z-scores at six months in rural Burkina Faso. Nested within MISAME-III, this sub-study examines the impact of BEP supplementation on maternal and infant gut microbiomes and their mediating role in birth outcomes and infant growth. A total of 152 mother-infant dyads (n = 71 intervention, n = 81 control) were included for metagenomic sequencing, with stool samples collected at the second and third trimesters, and at 1–2 and 5–6 months postpartum. BEP supplementation significantly altered maternal gut microbiome diversity, composition, and function, particularly those with immune-modulatory properties. Pathways linked to lipopolysaccharide biosynthesis were depleted and the species Bacteroides fragilis was enriched in BEP-supplemented mothers. Maternal BEP supplementation also accelerated infant microbiome changes and enhanced carbohydrate metabolism. Causal mediation analyses identified specific taxa mediating the effect of BEP on birth outcomes and infant growth. These findings suggest that maternal supplementation modulates gut microbiome composition and influences early-life development in resource-limited settings.

Date: 2025
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DOI: 10.1038/s41467-025-57838-y

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