• IMPORTANCE
    • 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.
  • OBJECTIVE
    • 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).
  • DESIGN, SETTING, AND PARTICIPANTS
    • 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.
  • EXPOSURES
    • Gut microbiome, fecal metabolome, and human milk feeding status at ages 3 months and 1 year.
  • MAIN OUTCOMES AND MEASURES
    • Age-, sex-, and height-specific SBP percentile, measured at ages 3 and 5 years.
  • RESULTS
    • 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.
  • CONCLUSIONS AND RELEVANCE
    • 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.