Exploring the Crosstalk: Nutrition, Microbiome, and Cardiometabolic Health

Exploring the Crosstalk: Nutrition, Microbiome, and Cardiometabolic Health 

The first 1,000 days establish a microbial and metabolic “set point” with lifelong implications for cardiometabolic health. Maternal–infant microbial sharing begins at birth, as microbes are transferred from both vaginal and gut reservoirs.¹ Research, including that from our group, has used strain-resolved metagenomics to reveal the vertical flow of maternal vaginal and fecal microbes, including Bifidobacterium longum subsp. infantis (B. infantis) and other human milk oligosaccharide (HMO) degrading bacteria that dominate the breastfed infant gut.¹ We have shown this transmission is strongly shaped by delivery mode, perinatal antibiotics, and early feeding practices, and can persist into toddlerhood.¹ Specifically, we have noted that cesarean delivery, early antibiotic exposure, and formula feeding consistently attenuate or delay colonization by bifidobacteria and Bacteroides, altering the early-life gut microbiota foundation.¹ 

The early-life gut microbiota is important for nutrition and cardiometabolic health outcomes. We have shown that early-life gut microbes and the metabolites they produce are associated with cardiometabolic measures of inflammation,² adiposity,³ and blood pressure⁴ in toddlerhood and beyond. Furthermore, these microbes may modify the effects of diet on these outcomes. For example, the cardiometabolic effects of breastmilk and HMOs appear to partially depend on early-life gut microbes, including B. infantis and other bifidobacteria.⁴ We have shown that the protective associations of breastmilk with child blood pressure are stronger among infants colonized by B. infantis, which may be mediated by production of the SCFA acetic acid.⁴ In contrast, association of breastfeeding with blood pressure are attenuated among infants that lack of B. infantis.⁴ Microbiota-specific diet effects have also been shown for other, non-HMO, dietary fibers. Ongoing and future studies that distinguish effect modification (diet altering the impact of the microbiome on outcomes) from mediation (diet shaping the microbiome to influence outcomes) are invaluable for providing causal insight into microbe-health outcome associations.  

Intervention strategies focused on restoring perturbed infant microbiomes, before these ecosystems become “adult like” are critical. We have shown that vaginal seeding after cesarean delivery may partially reinstate maternal microbial transmission,⁵ and gut microbiota from vaginally-seeded offspring can improve cardiometabolic outcomes, including intra-abdominal adiposity, in germ-free murine models.⁶ However, evidence remains limited as to the long-term health effects of early-life microbiome transplant interventions in humans. Synbiotic approaches that pair B. infantis with prebiotic fiber (e.g., HMOs) are another approach, with studies showing that these interventions promote colonization of beneficial microbes, production of short-chain fatty acids, and reduction of inflammation. Multi-pronged, microbiome-informed interventions may also hold promise for health-promoting microbiome restoration. We recently demonstrated that a personalized, microbiome-informed and coach-directed intervention that included breastfeeding tips, selecting microbiome-friendly formulas, prudent use of antimicrobials and probiotics, and responsive complementary feeding, resulted in a beneficial shift in microbiome profiles.⁷ 

Together, these lines of evidence converge on a central insight: targeted nutrition during the early-life window of microbial plasticity can meaningfully influence maternal–infant microbial transmission, shape metabolic programming, enhance the beneficial effects of diet, and thus optimize cardiometabolic health. By leveraging mechanistic understanding into intervention design, nutrition and microbiome science offers compelling evidence, along with testable approaches, to primordial prevention. Translational pathways extend from maternity care practices and antibiotic stewardship to personalized, microbiome-informed, coach-directed complementary feeding guidance. The integration of microbiome-targeted strategies into early-life precision nutrition represents a frontier in early-life prevention of cardiometabolic disease. 

REFERENCES 

1. Liu T, Kress AM, Debelius J, et al. Maternal vaginal and fecal microbiota in later pregnancy contribute to child fecal microbiota development in the ECHO cohort. iScience. Apr 18 2025;28(4):112211. doi:10.1016/j.isci.2025.112211 

2. Bohn B, Tilves C, Chen Y, et al. Associations of gut microbiota features and circulating metabolites with systemic inflammation in children. BMJ Open Gastroenterol. Aug 29 2024;11(1)doi:10.1136/bmjgast-2024-001470 

3. Chen Y, Tilves C, Bohn B, et al. Gut microbiota and microbial metabolites are associated with body composition in 5-year-old children: A cross-sectional study in the Gen3G cohort. Pediatr Obes. Jun 2025;20(6):e70007. doi:10.1111/ijpo.70007 

4. Liu T, Stokholm J, Zhang M, et al. Infant Gut Microbiota and Childhood Blood Pressure: Prospective Associations and the Modifying Role of Breastfeeding. J Am Heart Assoc. Mar 4 2025;14(5):e037447. doi:10.1161/JAHA.124.037447 

5. Mueller NT, Differding MK, Sun H, et al. Maternal Bacterial Engraftment in Multiple Body Sites of Cesarean Section Born Neonates after Vaginal Seeding-a Randomized Controlled Trial. mBio. Jun 27 2023;14(3):e0049123. doi:10.1128/mbio.00491-23 

6. Namasivayam S, Tilves C, Ding H, et al. Fecal transplant from vaginally seeded infants decreases intraabdominal adiposity in mice. Gut Microbes. Jan-Dec 2024;16(1):2353394. doi:10.1080/19490976.2024.2353394 

7. Nieto PA, Nakama C, Trachsel J, et al. Improving immune-related health outcomes post-cesarean birth with a gut microbiome-based program: A randomized controlled trial. Pediatr Allergy Immunol. Sep 2025;36(9):e70182. doi:10.1111/pai.70182