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Epidemiology and Population Health

Association between gut microbiota at 3.5 years of age and body mass index at 5 years: results from two French nationwide birth cohorts

International Journal of Obesity volume 48, pages 503–511 (2024)Cite this article

Subjects

Abstract

Background/objectives

The relationship between gut microbiota and changes in body mass index (BMI) or pediatric overweight in early life remains unclear, and information regarding the preterm population is scarce. This study aimed to investigate how the gut microbiota at 3.5 years of age is associated with (1) later BMI at 5 years, and (2) BMI z-score variations between 2 and 5 years in children from two French nationwide birth cohorts.

Subjects/methods

Bacterial 16S rRNA gene sequencing was performed to profile the gut microbiota at 3.5 years of age in preterm children (n = 143, EPIPAGE 2 cohort) and late preterm/full-term children (n = 369, ELFE cohort). The predicted abundances of metabolic functions were computed using PICRUSt2. Anthropometric measurements were collected at 2 and 5 years of age during medical examinations or retrieved from children’s health records. Statistical analyses included multivariable linear and logistic regressions, random forest variable selection, and MiRKAT.

Results

The Firmicutes to Bacteroidetes (F/B) ratio at 3.5 years was positively associated with the BMI z-score at 5 years. Several genera were positively ([Eubacterium] hallii group, Fusicatenibacter, and [Eubacterium] ventriosum group) or negatively (Eggerthella, Colidextribacter, and Ruminococcaceae CAG-352) associated with the BMI z-scores at 5 years. Some genera were also associated with variations in the BMI z-scores between 2 and 5 years of age. Predicted metabolic functions, including steroid hormone biosynthesis, biotin metabolism, glycosaminoglycan degradation, and amino sugar and nucleotide sugar metabolism, were associated with lower BMI z-scores at 5 years. The unsaturated fatty acids biosynthesis pathway was associated with higher BMI z-scores.

Conclusions

These findings indicate that the gut microbiota at 3.5 years is associated with later BMI during childhood, independent of preterm or term birth, suggesting that changes in the gut microbiota that may predispose to adult obesity begin in early childhood.

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Fig. 1: Gut microbiota genera at 3.5 years of age associated with BMI z-score and weight status at 5 years of age.
Fig. 2: KEGG metabolic pathways of 3.5 years gut microbiota associated with BMI z-score and weight status at 5 years of age.

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Data availability

The data from the ELFE and EPIPAGE 2 cohorts cannot be made publicly available for ethical reasons. They are available upon reasonable request from the authors upon reasonable request and under data-security conditions. The 16S rRNA gene reads are publicly available from the National Center for Biotechnology Information Sequence Read Archive (SRA) under the Bioproject accession number PRJNA907285.

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Funding

The ELFE cohort is a joint project between the French Institute for Demographic Studies (INED) and the National Institute of Health and Medical Research (INSERM), in partnership with the French blood transfusion service (Etablissement Français du Sang, EFS), Santé publique France, the National Institute for Statistics and Economic Studies (INSEE), the Direction Générale de la Santé (DGS, part of the Ministry of Health and Social Affairs), the Direction Générale de la Prévention des Risques (DGPR, Ministry for the Environment), the Direction de la Recherche, des Etudes, de l’Evaluation et des Statistiques (DREES, Ministry of Health and Social Affairs), the Département des Etudes, de la Prospective et des Statistiques (DEPS, Ministry of Culture), and the Caisse Nationale des Allocations Familiales (CNAF), with the support of the Ministry of Higher Education and Research and the Institut national de la Jeunesse et de l’Education Populaire (INJEP). The ELFE cohort receives a government grant managed by the National Research Agency under the “Investissements d’avenir” program (ANR-11-EQPX-0038, ANR-19-COHO-0001). The EPIPAGE 2 cohort was funded by the French Institute of Public Health and its partners: the French Health Ministry, The National Institute of Health and Medical Research, the National Institute of Cancer, and the National Solidarity Fund for Autonomy, the National Research Agency under the French Equipex program of “Investissements d’avenir” (ANR-11-EQPX-0038, ANR-19-COHO-0001), and the PremUp foundation. The EPIFLORE ancillary study has been funded by the French National Agency for Research (ANR-12-BSV3–0025), and the Nestec Research Center (Vers-chez-les-Blanc, Switzerland) for the constitution of the collection of stools. The 16S rRNA sequencing was funded by the Biostime Institute for Nutrition and Care-Geneva (BINC-Geneva).

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Author notes

  1. These authors contributed equally: Julio Aires, Marie-Aline Charles.

Authors and Affiliations

  1. Université Paris Cité et Université Sorbonne Paris Nord, Inserm, INRAE, Centre de Recherche en Épidémiologie et StatistiqueS (CRESS), F-75004, Paris, France

    Gaël Toubon, Pierre-Yves Ancel & Marie-Aline Charles

  2. Université Paris Cité, INSERM, UMR-S 1139, Physiopathologie et Pharmacotoxicologie Placentaire Humaine Microbiote Pré & Postnatal (3PHM), F-75006, Paris, France

    Gaël Toubon, Marie-José Butel, Johanne Delannoy & Julio Aires

  3. FHU PREMA, « Fighting Prematurity », F-75006, Paris, France

    Gaël Toubon, Marie-José Butel, Johanne Delannoy, Pierre-Yves Ancel & Julio Aires

  4. INRAE, UMR 1280, Physiologie des Adaptations Nutritionnelles (PhAN), Centre d’investigation clinique 1413, Centre hospitalo-universitaire de Nantes, F-44300, Nantes, France

    Jean-Christophe Rozé

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Contributions

J-CR, M-JB, M-AC, P-YA, and JA were responsible for data collection. GT, M-JB, M-AC, and JA designed the research. GT and JD analyzed the data. GT drafted the manuscript and J-CR, M-JB, M-AC, P-YA, JA, and JD contributed to writing the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Julio Aires or Marie-Aline Charles.

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Toubon, G., Butel, MJ., Rozé, JC. et al. Association between gut microbiota at 3.5 years of age and body mass index at 5 years: results from two French nationwide birth cohorts. Int J Obes 48, 503–511 (2024). https://doi.org/10.1038/s41366-023-01442-x

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