Dynamic Associations of Milk Components With the Infant Gut Microbiome and Fecal Metabolites in a Mother-Infant Model by Microbiome, NMR Metabolomic, and Time-Series Clustering Analyses

Yosuke Komatsu; Daiki Kumakura; Namiko Seto; Hirohisa Izumi; Yasuhiro Takeda; Yuki Ohnishi; Shinji Nakaoka; Tomoyasu Aizawa

doi:10.3389/fnut.2021.813690

Dynamic Associations of Milk Components With the Infant Gut Microbiome and Fecal Metabolites in a Mother-Infant Model by Microbiome, NMR Metabolomic, and Time-Series Clustering Analyses

Front Nutr. 2022 Jan 7:8:813690. doi: 10.3389/fnut.2021.813690. eCollection 2021.

Authors

Yosuke Komatsu^{1

2

3}, Daiki Kumakura¹, Namiko Seto², Hirohisa Izumi^{2

3}, Yasuhiro Takeda^{2

3}, Yuki Ohnishi^{1

4}, Shinji Nakaoka^{1

4}, Tomoyasu Aizawa^{1

4}

Affiliations

¹ Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
² Health Care and Nutritional Science Institute, Morinaga Milk Industry Co. Ltd., Zama, Japan.
³ Center for Food and Medical Innovation Promotion, Institute for the Promotion of Business-Regional Collaboration of Hokkaido University, Sapporo, Japan.
⁴ Department of Advanced Transdisciplinary Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.

Abstract

Background: The gut microbiome and fecal metabolites of breastfed infants changes during lactation, and are influenced by breast milk components. This study aimed to investigate dynamic associations of milk components with the infant gut microbiome and fecal metabolites throughout the lactation period in a mother-infant model. Methods: One month after delivery, breast milk and subsequent infant feces were collected in a pair for 5 months from a mother and an exclusively breastfed infant. Composition of the fecal microbiome was determined with 16S rRNA sequencing. Low-molecular-weight metabolites, including human milk oligosaccharides (HMOs), and antibacterial proteins were measured in feces and milk using ¹H NMR metabolomics and enzyme-linked immunosorbent assays. The association of milk bioactive components with the infant gut microbiome and fecal metabolites was determined with Python clustering and correlation analyses. Results: The HMOs in milk did not fluctuate throughout the lactation period. However, they began to disappear in infant feces at the beginning of month 4. Notably, at this time-point, a bifidobacterium species switching (from B. breve to B. longum subsp. infantis) occurred, accompanied by fluctuations in several metabolites including acetate and butyrate in infant feces. Conclusions: Milk bioactive components, such as HMOs, might play different roles in the exclusively breastfed infants depending on the lactation period.

Keywords: NMR metabolomics; bioactive component; breast milk; human milk oligosaccharide; infant fecal metabolites; infant gut microbiome; time-series clustering analysis.