Gut microbiome function and composition in infants from rural Kenya and association with human milk oligosaccharides

ABSTRACT

The gut microbiota evolves rapidly after birth, responding dynamically to environmental factors and playing a key role in short- and long-term health. Lifestyle and rurality have been shown to contribute to differences in the gut microbiome, including Bifidobacterium levels, between infants. We studied the composition, function and variability of the gut microbiomes of 6- to 11-month-old Kenyan infants (n = 105). Shotgun metagenomics showed Bifidobacterium longum to be the dominant species. A pangenomic analysis of B. longum in gut metagenomes revealed a high prevalence of B. longum subsp. infantis (B. infantis) in Kenyan infants (80%), and possible co-existence of this subspecies with B. longum subsp. longum. Stratification of the gut microbiome into community (GMC) types revealed differences in composition and functional features. GMC types with a higher prevalence of B. infantis and abundance of B. breve also had a lower pH and a lower abundance of genes encoding pathogenic features. An analysis of human milk oligosaccharides (HMOs) classified the human milk (HM) samples into four groups defined on the basis of secretor and Lewis polymorphisms revealed a higher prevalence of HM group III (Se+, Le-) (22%) than in most previously studied populations, with an enrichment in 2′-fucosyllactose. Our results show that the gut microbiome of partially breastfed Kenyan infants over the age of six months is enriched in bacteria from the Bifidobacterium community, including B. infantis, and that the high prevalence of a specific HM group may indicate a specific HMO-gut microbiome association. This study sheds light on gut microbiome variation in an understudied population with limited exposure to modern microbiome-altering factors.

KEYWORDS:

• Kenyan infants
• gut microbiome
• breastfeeding
• bifidobacterium
• community types

Acknowledgments

We thank the mothers and infants in the study, field workers and E. Mwasi from Msambweni County Referral Hospital (Msambweni, Kenya), as well as C. Zeder, A. Krzystek, T. Christ (ETH Zurich, Switzerland) and J. Erhardt (Willstaett, Germany) for providing support for laboratory and data analyses. We thank R. Berends, A. Botma, and L. Kaptein from Danone Nutricia Research (Utrecht, The Netherlands) for clinical study support. We thank M. Mank (Danone Nutricia Research, Utrecht, The Netherlands) and E. Rapp (glyXera GmbH, Magdeburg, Germany) for fruitful discussions on HMOs and critical reading of the manuscript.

Data Availability Statement

Metagenomic sequences associated with this project were deposited in EMBL under BioProject accession no. PRJEB52748. The source codes used in this study are available from GitHub (github.com/danone/Kenya.study)

Disclosure statement

M.D., R.B.S., and B.S. are Danone Nutricia Research employees and R.K. is an employee of glyXera GmbH, Magdeburg, Germany.

Ethics approval and consent to participate

Caregivers gave informed consent with either a written signature or a fingerprint. The study protocol was approved by the ethical review committee of ETH Zurich, Switzerland (EK 2018-N-84), and the Institutional Ethics and Review Committee of the Jomo Kenyatta University of Agriculture and Technology, Kenya (JKU/2/4/896B). The trial is registered at clinicaltrials.gov as NCT03894358.

Contributions

M.B.Z., R.B.S., N.M., N.U.S. and M.A.U. designed the clinical study. N.M, M.A.U., S.K. and S.N. conducted the clinical study. M.D. and R.B.S. designed the gut microbiota study. R.K. performed the HMO analysis. M.D., E.C. and R.B.S. supervised the analysis. E.C.Z. and A.H-V. performed the bioinformatic and statistical analysis. M.D. wrote the first draft with inputs from E.C., R.K., R.B.S. All authors were involved in data interpretation and discussion of the results. All the authors edited and approved the final manuscript for submission.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2178793

Additional information

Funding

This study was funded by Danone Nutricia Research.