Free threonine in human breast milk is related to infant intestinal microbiota composition

Monika Riederer; Natascha Schweighofer; Slave Trajanoski; Claudia Stelzer; Miriam Zehentner; Bianca Fuchs-Neuhold; Karl Kashofer; Johannes A Mayr; Marlies Hörmann-Wallner; Sandra Holasek; Moenie van der Kleyn

doi:10.1007/s00726-021-03057-w

Free threonine in human breast milk is related to infant intestinal microbiota composition

Amino Acids. 2022 Mar;54(3):365-383. doi: 10.1007/s00726-021-03057-w. Epub 2021 Sep 3.

Affiliations

¹ Institute of Biomedical Science, University of Applied Sciences JOANNEUM, Graz, Austria. monika.riederer@fh-joanneum.at.
² Division of Endocrinology and Diabetology, Medical University Graz, Graz, Austria.
³ Core Facility Computational Bioanalytics, Center for Medical Research (ZMF), Medical University of Graz, Graz, Austria.
⁴ Institute of Biomedical Science, University of Applied Sciences JOANNEUM, Graz, Austria.
⁵ Institute of Dietetics and Nutrition, Health Perception Lab, University of Applied Sciences JOANNEUM, Graz, Austria.
⁶ Diagnostic and Research Institute of Pathology, Medical University of Graz, Auenbruggerpl. 2, 8036, Graz, Austria.
⁷ Department of Pediatrics, Salzburger Landeskliniken and Paracelsus Medical University, Salzburg, Austria.
⁸ Department of Pathophysiology, Medical University Graz, Graz, Austria.
⁹ Institute of Midwifery, University of Applied Sciences JOANNEUM, Graz, Austria.

Abstract

Background: Accumulating evidence indicates that free amino acids (FAA) might be bioactive compounds with potential immunomodulatory capabilities. However, the FAA composition in human milk is still poorly characterized with respect to its correlation to maternal serum levels and its physiological significance for the infant. Studies addressing the relation of human milk FAA to the infants' intestinal microbiota are still missing.

Methods: As part of a pilot study, maternal serum and breast milk FAA concentrations as well as infant intestinal microbiota (16S rRNA) were determined 2 months after birth. The study cohort consisted of 41 healthy mothers and their term delivered, healthy infants with normal birthweight. The relationship between maternal serum and milk FAA was determined by correlation analyses. Associations between (highly correlated) milk FAA and infant intestinal beta diversity were tested using PERMANOVA, LefSe and multivariate regression models adjusted for common confounders.

Results: Seven breast milk FAA correlated significantly with serum concentrations. One of these, threonine showed a negative association with abundance of members of the class Gammaproteobacteria (R²adj = 17.1%, p = 0.006; β= - 0.441). In addition, on the level of families and genera, threonine explained 23.2% of variation of the relative abundance of Enterobacteriaceae (R²adj; p = 0.001; β = - 0.504) and 11.1% of variability in the abundance of Escherichia/Shigella (R²adj, p = 0.025; β = - 0.368), when adjusted for confounders.

Conclusion: Our study is the first to suggest potential interactions between breast milk FAA and infant gut microbiota composition during early lactation. The results might be indicative of a potential protective role of threonine against members of the Enterobacteriaceae family in breast-fed infants. Still, results are based on correlation analyses and larger cohorts are needed to support the findings and elucidate possible underlying mechanisms to assess the complex interplay between breast milk FAA and infant intestinal microbiota in detail.

Keywords: Breast milk; Enterobacteriales; Free amino acids; Gammaproteobacteria; Human; Infant; Microbiota; Threonine.

MeSH terms

Female
Gastrointestinal Microbiome* / genetics
Humans
Infant
Milk, Human* / chemistry
Milk, Human* / metabolism
Milk, Human* / microbiology
Pilot Projects
RNA, Ribosomal, 16S / genetics
Threonine / metabolism

Substances

RNA, Ribosomal, 16S
Threonine

Grants and funding

839098/Österreichische Forschungsförderungsgesellschaft