Human milk-associated bacterial communities associate with the infant gut microbiome over the first year of life

Sara N Lundgren; Juliette C Madan; Margaret R Karagas; Hilary G Morrison; Brock C Christensen; Anne G Hoen

doi:10.3389/fmicb.2023.1164553

Human milk-associated bacterial communities associate with the infant gut microbiome over the first year of life

Front Microbiol. 2023 Apr 17:14:1164553. doi: 10.3389/fmicb.2023.1164553. eCollection 2023.

Authors

Sara N Lundgren¹, Juliette C Madan^{1

2

3}, Margaret R Karagas^{1

4}, Hilary G Morrison⁵, Brock C Christensen^{1

4

6}, Anne G Hoen^{1

7

8}

Affiliations

¹ Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States.
² Department of Pediatrics, Children's Hospital at Dartmouth, Lebanon, NH, United States.
³ Department of Psychiatry, Children's Hospital at Dartmouth, Lebanon, NH, United States.
⁴ Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States.
⁵ Josephine Bay Paul Center, Marine Biological Laboratory, Woods Hole, MA, United States.
⁶ Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States.
⁷ Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States.
⁸ Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States.

Abstract

Introduction: Microbial communities inhabiting the human infant gut are important for immune system development and lifelong health. One critical exposure affecting the bacterial colonization of the infant gut is consumption of human milk, which contains diverse microbial communities and prebiotics. We hypothesized that human milk-associated microbial profiles are associated with those of the infant gut.

Methods: Maternal-infant dyads enrolled in the New Hampshire Birth Cohort Study (n = 189 dyads) contributed breast milk and infant stool samples collected approximately at 6 weeks, 4 months, 6 months, 9 months, and 12 months postpartum (n = 572 samples). Microbial DNA was extracted from milk and stool and the V4-V5 region of the bacterial 16S rRNA gene was sequenced.

Results: Clustering analysis identified three breast milk microbiome types (BMTs), characterized by differences in Streptococcus, Staphylococcus, Pseudomonas, Acinetobacter, and microbial diversity. Four 6-week infant gut microbiome types (6wIGMTs) were identified, differing in abundances of Bifidobacterium, Bacteroides, Clostridium, Streptococcus, and Escherichia/Shigella, while two 12-month IGMTs (12mIGMTs) differed primarily by Bacteroides presence. At 6 weeks, BMT was associated with 6wIGMT (Fisher's exact test value of p = 0.039); this association was strongest among infants delivered by Cesarean section (Fisher's exact test value of p = 0.0028). The strongest correlations between overall breast milk and infant stool microbial community structures were observed when comparing breast milk samples to infant stool samples collected at a subsequent time point, e.g., the 6-week breast milk microbiome associated with the 6-month infant gut microbiome (Mantel test Z-statistic = 0.53, value of p = 0.001). Streptoccous and Veillonella species abundance were correlated in 6-week milk and infant stool, and 4- and 6-month milk Pantoea species were associated with infant stool Lachnospiraceae genera at 9 and 12 months.

Discussion: We identified clusters of human milk and infant stool microbial communities that were associated in maternal-infant dyads at 6 weeks of life and found that milk microbial communities were more strongly associated with infant gut microbial communities in infants delivered operatively and after a lag period. These results suggest that milk microbial communities have a long-term effect on the infant gut microbiome both through sharing of microbes and other molecular mechanisms.

Keywords: breast milk microbiome; breastfeeding; cesarean delivery; infant gut microbiome; microbial co-occurrence.