IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-57838-y.html
   My bibliography  Save this article

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

Author

Listed:
  • Lishi Deng

    (Ghent University)

  • Steff Taelman

    (Ghent University
    Ghent University
    BioLizard nv)

  • Matthew R. Olm

    (Stanford University School of Medicine
    University of Colorado Boulder)

  • Laeticia Celine Toe

    (Ghent University
    Unité Nutrition et Maladies Métaboliques)

  • Eva Balini

    (BioLizard nv)

  • Lionel Olivier Ouédraogo

    (Ghent University
    Centre Muraz)

  • Yuri Bastos-Moreira

    (Ghent University
    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
    International Food Policy Research Institute (IFPRI))

  • Michiel Stock

    (Ghent University)

  • Patrick Kolsteren

    (Ghent University)

  • Justin L. Sonnenburg

    (Stanford University School of Medicine
    Chan Zuckerberg Biohub
    Stanford University School of Medicine)

  • Carl Lachat

    (Ghent University)

  • Trenton Dailey-Chwalibóg

    (Ghent University
    Agence de Formation de Recherche et d’Expertise en Santé pour l’Afrique (AFRICSanté))

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.

Suggested Citation

  • 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. H, 2025. "Maternal balanced energy-protein supplementation reshapes the maternal gut microbiome and enhances carbohydrate metabolism in infants: a randomized controlled trial," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57838-y
    DOI: 10.1038/s41467-025-57838-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-57838-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-57838-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Sarkis K. Mazmanian & June L. Round & Dennis L. Kasper, 2008. "A microbial symbiosis factor prevents intestinal inflammatory disease," Nature, Nature, vol. 453(7195), pages 620-625, May.
    2. Sathish Subramanian & Sayeeda Huq & Tanya Yatsunenko & Rashidul Haque & Mustafa Mahfuz & Mohammed A. Alam & Amber Benezra & Joseph DeStefano & Martin F. Meier & Brian D. Muegge & Michael J. Barratt & , 2014. "Persistent gut microbiota immaturity in malnourished Bangladeshi children," Nature, Nature, vol. 510(7505), pages 417-421, June.
    3. Gruber, Susan & Laan, Mark van der, 2012. "tmle: An R Package for Targeted Maximum Likelihood Estimation," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 51(i13).
    4. Zachary D Kurtz & Christian L Müller & Emily R Miraldi & Dan R Littman & Martin J Blaser & Richard A Bonneau, 2015. "Sparse and Compositionally Robust Inference of Microbial Ecological Networks," PLOS Computational Biology, Public Library of Science, vol. 11(5), pages 1-25, May.
    5. Christopher J. Stewart & Nadim J. Ajami & Jacqueline L. O’Brien & Diane S. Hutchinson & Daniel P. Smith & Matthew C. Wong & Matthew C. Ross & Richard E. Lloyd & HarshaVardhan Doddapaneni & Ginger A. M, 2018. "Temporal development of the gut microbiome in early childhood from the TEDDY study," Nature, Nature, vol. 562(7728), pages 583-588, October.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ana Popovic & Celine Bourdon & Pauline W. Wang & David S. Guttman & Sajid Soofi & Zulfiqar A. Bhutta & Robert H. J. Bandsma & John Parkinson & Lisa G. Pell, 2021. "Micronutrient supplements can promote disruptive protozoan and fungal communities in the developing infant gut," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Duo Jiang & Thomas Sharpton & Yuan Jiang, 2021. "Microbial Interaction Network Estimation via Bias-Corrected Graphical Lasso," Statistics in Biosciences, Springer;International Chinese Statistical Association, vol. 13(2), pages 329-350, July.
    3. Fanette Fontaine & Sondra Turjeman & Karel Callens & Omry Koren, 2023. "The intersection of undernutrition, microbiome, and child development in the first years of life," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    4. Ruairi C. Robertson & Thaddeus J. Edens & Lynnea Carr & Kuda Mutasa & Ethan K. Gough & Ceri Evans & Hyun Min Geum & Iman Baharmand & Sandeep K. Gill & Robert Ntozini & Laura E. Smith & Bernard Chasekw, 2023. "The gut microbiome and early-life growth in a population with high prevalence of stunting," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Guilherme Fahur Bottino & Kevin S. Bonham & Fadheela Patel & Shelley McCann & Michal Zieff & Nathalia Naspolini & Daniel Ho & Theo Portlock & Raphaela Joos & Firas S. Midani & Paulo Schüroff & Anubhav, 2025. "Early life microbial succession in the gut follows common patterns in humans across the globe," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    6. Natalia Di Tommaso & Antonio Gasbarrini & Francesca Romana Ponziani, 2021. "Intestinal Barrier in Human Health and Disease," IJERPH, MDPI, vol. 18(23), pages 1-23, December.
    7. Li Zhang & Karen R. Jonscher & Zuyuan Zhang & Yi Xiong & Ryan S. Mueller & Jacob E. Friedman & Chongle Pan, 2022. "Islet autoantibody seroconversion in type-1 diabetes is associated with metagenome-assembled genomes in infant gut microbiomes," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. Ronald Herrera & Ursula Berger & Ondine S. Von Ehrenstein & Iván Díaz & Stella Huber & Daniel Moraga Muñoz & Katja Radon, 2017. "Estimating the Causal Impact of Proximity to Gold and Copper Mines on Respiratory Diseases in Chilean Children: An Application of Targeted Maximum Likelihood Estimation," IJERPH, MDPI, vol. 15(1), pages 1-15, December.
    9. Zhang, Yingheng & Li, Haojie & Ren, Gang, 2025. "Analysing the role of traffic volume as mediator in transport policy evaluation with causal mediation analysis and targeted learning," Transportation Research Part A: Policy and Practice, Elsevier, vol. 192(C).
    10. Dina in ‘t Zandt & Zuzana Kolaříková & Tomáš Cajthaml & Zuzana Münzbergová, 2023. "Plant community stability is associated with a decoupling of prokaryote and fungal soil networks," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    11. Li, Lianwei & Li, Wendy & Zou, Quan & Ma, Zhanshan (Sam), 2020. "Network analysis of the hot spring microbiome sketches out possible niche differentiations among ecological guilds," Ecological Modelling, Elsevier, vol. 431(C).
    12. Youmi Suk, 2024. "A Within-Group Approach to Ensemble Machine Learning Methods for Causal Inference in Multilevel Studies," Journal of Educational and Behavioral Statistics, , vol. 49(1), pages 61-91, February.
    13. Qin Liu & Qi Su & Fen Zhang & Hein M. Tun & Joyce Wing Yan Mak & Grace Chung-Yan Lui & Susanna So Shan Ng & Jessica Y. L. Ching & Amy Li & Wenqi Lu & Chenyu Liu & Chun Pan Cheung & David S. C. Hui & P, 2022. "Multi-kingdom gut microbiota analyses define COVID-19 severity and post-acute COVID-19 syndrome," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    14. Susan Gruber & Mark J. van der Laan, 2013. "An Application of Targeted Maximum Likelihood Estimation to the Meta-Analysis of Safety Data," Biometrics, The International Biometric Society, vol. 69(1), pages 254-262, March.
    15. Michael Schomaker & Christian Heumann, 2020. "When and when not to use optimal model averaging," Statistical Papers, Springer, vol. 61(5), pages 2221-2240, October.
    16. Veronica Sciannameo & Gian Paolo Fadini & Daniele Bottigliengo & Angelo Avogaro & Ileana Baldi & Dario Gregori & Paola Berchialla, 2022. "Assessment of Glucose Lowering Medications’ Effectiveness for Cardiovascular Clinical Risk Management of Real-World Patients with Type 2 Diabetes: Targeted Maximum Likelihood Estimation under Model Mi," IJERPH, MDPI, vol. 19(22), pages 1-13, November.
    17. Jason Saba & Katia Flores & Bailey Marshall & Michael D. Engstrom & Yikai Peng & Atharv S. Garje & Laurie E. Comstock & Robert Landick, 2024. "Bacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    18. John Matta & Virender Singh & Trevor Auten & Prashant Sanjel, 2023. "Inferred networks, machine learning, and health data," PLOS ONE, Public Library of Science, vol. 18(1), pages 1-20, January.
    19. Ziyun Xu & Éric Archambault, 2015. "Chinese interpreting studies: structural determinants of MA students’ career choices," Scientometrics, Springer;Akadémiai Kiadó, vol. 105(2), pages 1041-1058, November.
    20. Alice Risely & Kerstin Wilhelm & Tim Clutton-Brock & Marta B. Manser & Simone Sommer, 2021. "Diurnal oscillations in gut bacterial load and composition eclipse seasonal and lifetime dynamics in wild meerkats," Nature Communications, Nature, vol. 12(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57838-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.