(PTFS16-04-24) Human Milk Oligosaccharide Metabolizing Gene Abundance and Diversity in Infants

Objectives: This study aims to assess the diversity of human milk oligosaccharide (HMO) metabolizing genes in the infant gut microbiome and associate gene patterns with participant characteristics. We hypothesized that gut microbiotas of human-milk fed infants would contain a greater abundance and diversity of HMO metabolizing genes compared to those of non-human milk fed infants. We also hypothesized that mode of delivery will have no significant impact on HMO-metabolizing gene concentrations in the infant gut.

Methods: Pregnant women enrolled in the Michigan Archive for Research on Child Health (MARCH) and later provided questionnaire responses and fecal samples when their infants were 1 (n=38) and 3 mos (n=77) old. All fecal samples underwent DNA extraction. DNA from 3 mos old stool samples was sequenced. Quantitative real-time PCR was used to analyze HMO-metabolizing gene abundance and diversity in relation to mode of delivery (1 mos), diet (1 and 3 mos) or eczema (3 mos). HMO gene abundance was compared by characteristic using the Kruskal Wallis test.

Results: HMO metabolizing gene (Sia, B breve, GH750, and gBif) abundance was similar for vaginally and cesarean delivered infants. The abundance of Sia was significantly increased in 1 mos human-milk fed infants (p < 0.10), and this was demonstrated by mean CT value analysis between human and non-human milk fed infants. The abundance of other HMO genes was similar between feeding groups. Though three clusters of 3mos old participants emerged upon analysis of HMO metabolizing genes using whole genome sequencing data, these clusters were not associated with infant diet.

Conclusions: The results suggest that infant feeding practices, rather than mode of delivery, drive HMO metabolizing gene abundance, specifically Sia, a gene encoding a sialidase. Assessing the effects of human milk on the gut microbiome can elucidate the role of diet in improving child health and strengthening long-term immunity.

Funding Sources: This research was funded in part by the National Institute of Allergy and Infectious Disease, the Office of the Director at the National Institutes of Health, the Michigan Health Endowment Fund, and other institutional funds.