High blood pressure (BP) in childhood is an important public health concern. Around 2 to 5% of children aged 6 years and older are affected by hypertension, with 18% of having elevated BP. Although hypertension is less commonly diagnosed in early childhood, BP levels tend to track from childhood into adulthood, where hypertension is a leading risk factor for cardiovascular disease. Early life determinants of BP remain insufficiently understood, limiting opportunities for prevention. Human milk feeding and infant gut microbiome are potentially modifiable early-life exposures that can influence cardiometabolic health. Bifidobacterium longum subsp infantis (B. infantis) is a human milk oligosaccharide (HMO)-degrading bacterium that can improve the biological benefits of breastfeeding by producing bioactive metabolites.
A study published in JAMA Netw Open aimed to investigate whether interactions between human milk feeding and infant gut microbiome, specifically B. infantis, are prospectively linked to infant fecal metabolites and systolic blood pressure (SBP) in early childhood. The researchers hypothesized that the SBP-lowering association of human milk would be stronger in infants harboring B. infantis and that microbial metabolites might partially mediate these associations.
This cohort study was conducted in the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study, which followed children from infancy to age 13 years in four Canadian cities. The analytic sample included 1,324 children (610 girls [46.1%]); 982 (74.2%) were delivered vaginally. Mothers had a mean age of 33.3±4.5 years, 74.0% were White, 14.1% Asian, and 11.9% other races/ethnicities. Most mothers had a college (73.9%) or graduate degree (19.5%). At 3 months, 799 infants (60.4%) were exclusively human milk-fed, 349 (26.4%) mixed-fed, and 174 (13.1%) not breastfed. 611 infants (47.3%) were still receiving human milk at 1 year. Stool samples were collected at about 3 months and one year for shotgun metagenomic sequencing and metabolomic profiling. BP was measured at ages 3 and 5 years; mean SBP percentiles were 74.6±21.3 at 3 years and 73.4±22.0 at 5 years. Mixed-effects models adjusted for maternal, perinatal, and child factors were used to examine associations and interactions.
The association between human milk feeding and childhood SBP differed significantly according to the presence of B. infantis at 3 months. In infants harboring B. infantis, exclusive human milk feeding was associated with a −17.16 percentile difference in SBP (95% confidence interval [CI]: −29.48 to −4.83) and mixed feeding with a −14.81 percentile difference (95% CI: −27.05 to −2.56), compared with no human milk. No significant associations were observed in infants without B. infantis. Among infants not receiving human milk at 3 months, the presence and higher relative abundance of B. infantis and B. bifidum were linked to higher SBP. No significant microbiome–feeding interactions were observed at 1 year, suggesting a critical window in early infancy. Microbial community analyses showed that the presence of B. infantis explained substantial variation in gut composition at 3 months, specifically in exclusively breastfed infants (R² = 12.60%, P = 0.001) compared with mixed-fed infants (R² = 6.61%, P = 0.001) and non-breastfed infants (R² = 0.67%, P = 0.27).
Metabolomic analyses detected 20 fecal metabolites at 3 months and 11 at 1 year associated with childhood SBP, mainly with SBP at 5 years. Positive associations were observed for metabolites such as succinate and creatinine at 3 months, while several lipid species showed inverse associations. Interactions between B. infantis and human milk feeding were linked to many SBP-related metabolites, which include creatinine and lipid metabolites. Short-chain fatty acids like acetate did not show significant links with SBP. Sensitivity analyses adjusting for gestational age, maternal smoking (7.8%), and child body mass index (BMI) did not materially change findings.
This large prospective cohort study showed that the association between human milk feeding and lower childhood SBP depends on the presence of specific gut microbes, specifically B. infantis, in early infancy. The findings suggest that HMO-degrading microbes enhance the cardiovascular benefits of breastfeeding and that microbial metabolic pathways established at 3 months of age may influence later BP. These results highlight the potential for precision nutrition strategies targeting the early-life gut microbiome to support long-term cardiovascular health, while underscoring the need for replication and mechanistic studies to confirm causality.
Reference: Liu T, Petersen C, Zhao N, et al. Human Milk and Infant Gut Microbiome in Association With Infant Fecal Metabolome and Child Blood Pressure. JAMA Netw Open. 2026;9(2):e2559385. doi:10.1001/jamanetworkopen.2025.59385
