Human Milk and Infant Gut Microbiome in Association With Infant Fecal Metabolome and Child Blood Pressure

Infant milk feeding type (eg, human milk vs formula) and infant gut microbes have each been associated with differences in microbial metabolites and childhood blood pressure; however, evidence remains limited regarding how specific infant gut microbes, at a species or strain level, in combination with milk feeding type, shape microbial metabolites and blood pressure.

To investigate whether human milk feeding and infant gut microbes, including Bifidobacterium longum subsp infantis (B infantis) and other milk-degrading microbes, are associated with infant fecal metabolites and childhood systolic blood pressure (SBP).

This cohort study was part of the Canadian Healthy Infant Longitudinal Development (CHILD) cohort study, a prospective multicenter, contemporary, population-based cohort of pregnant mothers and their offspring recruited between 2009 and 2012. Data were collected from 2009 to 2018 and analyzed from January to December 2024. Participants included a subset of children born at 35 weeks of gestation or later without congenital abnormalities or respiratory distress syndrome and with available data on gut microbiome, fecal metabolome, SBP, and covariates.

Gut microbiome, fecal metabolome, and human milk feeding status at ages 3 months and 1 year.

Age-, sex-, and height-specific SBP percentile, measured at ages 3 and 5 years.

A total of children (610 [46.1%] girls; 982 children [74.2%] delivered vaginally; mean [SD] maternal age at delivery, 33.3 [4.5] years) were included. At age 3 months, but not at age 1 year, human milk feeding and presence of B infantis showed interactive associations with infant fecal metabolites at ages 3 months and 1 year and SBP at ages 3 and 5 years. Among infants harboring B infantis at age 3 months, mixed feeding (difference, -14.81 [95% CI, -27.05 to -2.56] percentile) and exclusive human milk feeding (difference, -17.16 [95% CI, -29.48 to -4.83] percentile) were associated with a lower childhood SBP, whereas no association was observed among infants without B infantis. Several additional infant gut microbes (eg, Eggerthella lenta, Veillonella dispar) and fecal metabolites (eg, creatinine, succinic acid) also demonstrated feeding- or B infantis-dependent associations with childhood SBP.

In this cohort study, early-life interactions between human milk feeding and B infantis, among other bacteria, were associated with the infant fecal metabolome and childhood SBP, underscoring the potential importance of early-life nutrition-microbe interplay in cardiometabolic health.