Model Selection Reveals the Butyrate-Producing Gut Bacterium Coprococcus eutactus as Predictor for Language Development in 3-Year-Old Rural Ugandan Children

Remco Kort*, Job Schlösser, Alan R. Vazquez, Prudence Atukunda, Grace K.M. Muhoozi, Alex Paul Wacoo, Wilbert F.H. Sybesma, Ane C. Westerberg, Per Ole Iversen, Eric D. Schoen

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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Abstract

Introduction: The metabolic activity of the gut microbiota plays a pivotal role in the gut-brain axis through the effects of bacterial metabolites on brain function and development. In this study we investigated the association of gut microbiota composition with language development of 3-year-old rural Ugandan children.

Methods: We studied the language ability in 139 children of 36 months in our controlled maternal education intervention trial to stimulate children’s growth and development. The dataset includes 1170 potential predictors, including anthropometric and cognitive parameters at 24 months, 542 composition parameters of the children’s gut microbiota at 24 months and 621 of these parameters at 36 months. We applied a novel computationally efficient version of the all-subsets regression methodology and identified predictors of language ability of 36-months-old children scored according to the Bayley Scales of Infant and Toddler Development (BSID-III).

Results: The best three-term model, selected from more than 266 million models, includes the predictors Coprococcus eutactus at 24 months of age, Bifidobacterium at 36 months of age, and language development at 24 months. The top 20 four-term models, selected from more than 77 billion models, consistently include C. eutactus abundance at 24 months, while 14 of these models include the other two predictors as well. Mann–Whitney U tests suggest that the abundance of gut bacteria in language non-impaired children (n = 78) differs from that in language impaired children (n = 61). While anaerobic butyrate-producers, including C. eutactus, Faecalibacterium prausnitzii, Holdemanella biformis, Roseburia hominis are less abundant, facultative anaerobic bacteria, including Granulicatella elegans, Escherichia/Shigella and Campylobacter coli, are more abundant in language impaired children. The overall predominance of oxygen tolerant species in the gut microbiota was slightly higher in the language impaired group than in the non-impaired group (P = 0.09).

Conclusion: Application of the all-subsets regression methodology to microbiota data established a correlation between the relative abundance of the anaerobic butyrate-producing gut bacterium C. eutactus and language development in Ugandan children. We propose that the gut redox potential and the overall bacterial butyrate-producing capacity in the gut are important factors for language development.
Original languageEnglish
Article number681485
Pages (from-to)1-14
Number of pages14
JournalFrontiers in Microbiology
Volume12
Issue numberJune
DOIs
Publication statusPublished - 2 Jun 2021

Bibliographical note

Funding Information:
The study was approved by The AIDS Support Organization Research Ethics Committee (no. TASOREC/06/15-UG-REC-009) and by the Uganda National Council for Science and Technology (no. UNCST HS 1809) as well as by the Norwegian Regional Committee for Medical and Health Research Ethics (no. 2013/1833). Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.

Funding Information:
All mothers gave written or thumb-printed, informed consent to participate and could decline an interview or assessment at any time. The study was approved by The AIDS Support Organization Research Ethics Committee (no. TASOREC/06/15-UG-REC-009) and by the Uganda National Council for Science and Technology (no. UNCST HS 1809) as well as by the Norwegian Regional Committee for Medical and Health Research Ethics (no. 2013/1833). The trial was registered at clinicaltrials.gov (NCT02098031).

Funding Information:
This research was funded by the Vrije Universiteit Amsterdam (Amsterdam, Netherlands), and the Throne Holst Foundation (Oslo, Norway).

Publisher Copyright:
© Copyright © 2021 Kort, Schlösser, Vazquez, Atukunda, Muhoozi, Wacoo, Sybesma, Westerberg, Iversen and Schoen.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • all subsets regression
  • butyrate
  • Coprococcus eutactus
  • gut-brain-axis
  • language development
  • metagenomic aerotolerant predominance index
  • mixed integer optimization

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