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Gut Microbiota

The infant gut microbiota develops rapidly in early life and plays an important role in immune maturation, metabolic programming and epithelial barrier integrity.1,2 Early microbial colonisation is influenced by maternal health, antibiotic exposure, mode of delivery and infant feeding practices.3,4

Infants born by caesarean section typically demonstrate delayed colonisation with Bacteroides and reduced abundance of Bifidobacterium species compared with vaginally delivered infants, with differences detectable into later infancy.3 Early-life antibiotic exposure further alters microbial diversity and may reduce bifidobacterial abundance.4

Breastfeeding remains the biological reference standard for microbiota development. Human milk oligosaccharides selectively promote bifidobacterial species, supporting short-chain fatty acid production and contributing to gut barrier function and immune regulation.2

When infant formula is the primary source of nutrition, specific ingredients may influence microbial composition.

Prebiotic galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS) have been shown in randomised controlled trials and systematic reviews to increase Bifidobacterium abundance in formula-fed infants, lower stool pH and increase short-chain fatty acid production.5,6 Clinical studies report softer stool consistency and stool patterns more comparable to those observed in breastfed infants.5

The probiotic strain Bifidobacterium animalis subsp. lactis BB-12 has been evaluated in randomised controlled trials in healthy term infants, with findings synthesised in recent systematic reviews.7-9 Supplementation increases faecal bifidobacterial abundance and supports gastrointestinal tolerance in formula-fed infants.7,8 The 2026 ESPGHAN technical review concludes that probiotic effects in infant formula are strain-specific, with modest evidence for reduced functional gastrointestinal symptoms and selected infection outcomes in some populations, while emphasising heterogeneity across trials.9

Lactoferrin has been evaluated in randomised clinical trials, with recent reviews reporting modest and context-dependent effects on selected gastrointestinal and respiratory infection outcomes and mucosal immune responses in infants.10 Mechanistic and clinical studies also suggest potential influences on early microbial composition, including pathogen inhibition and effects on bifidobacteria, although findings are not consistently demonstrated.10

Overall, evidence supports the inclusion of well-characterised prebiotic and probiotic ingredients in infant formula to help modulate early microbial development when breastfeeding is not possible, while recognising that effects are ingredient-specific and not equivalent to the biological complexity of human milk.

References

  1. Stewart CJ, Ajami NJ, O’Brien JL, et al. Temporal development of the gut microbiome in early childhood. Nature. 2018;562:583-8. doi:10.1038/s41586-018-0617-x
  2. Lawson MAE, O’Neill IJ, Kujawska M, et al. Breast milk–derived human milk oligosaccharides promote bifidobacterial colonisation. Nat Commun. 2020;11:4588. doi:10.1038/s41396-019-0553-2
  3. Hoang DM, Levy EI, Vandenplas Y. The impact of caesarean section on the infant gut microbiome. Acta Paediatr. 2021;110:60-67. doi:10.1111/apa.15501
  4. Dierikx TH, Visser DH, Benninga MA, et al. The influence of prenatal and intrapartum antibiotics on intestinal microbiota colonisation in infants: a systematic review. J Infect. 2020;81:190-204. doi:10.1016/j.jinf.2020.05.002
  5. Vandenplas Y, De Greef E, Veereman G. Prebiotics in infant formula. Nutrients. 2020;12:1959. doi:10.4161/19490976.2014.972237
  6. Wiciński M, Sawicka E, Gębalski J, et al. Human milk oligosaccharides and prebiotics in infant nutrition. Nutrients. 2020;12:2663. doi:10.3390/nu12010266
  7. Bueno CPAR, Domínguez AC, Guyonnet D, Pouteau E. Health benefits of Bifidobacterium animalis subsp. lactis BB-12 in infants and children: a mini-review. Front Microbiol. 2026;17:1773473. doi:10.3389/fmicb.2026.1773473.
  8. Indrio F, Gutierrez-Castrellon P, Vandenplas Y, Dinleyici EC, Francavilla R, Mantovani MP, Grillo A, Beghetti I, Corvaglia L, Aceti A. Health effects of infant formula supplemented with probiotics or synbiotics in infants and toddlers: systematic review with network meta-analysis. Nutrients. 2022;14(23):5175. doi:10.3390/nu14235175
  9. Dinleyici EC, Szajewska H, Hojsak I, et al. Technical review by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications on the health outcomes of infant formula supplemented with probiotics. J Pediatr Gastroenterol Nutr. 2026;82(1):235-251. doi:10.1002/jpn3.70068
  10. Miyakawa M, Oda H, Tanaka M. Clinical research review: usefulness of bovine lactoferrin in child health. BioMetals. 2023;36(3):473-489. doi:10.1007/s10534-022-00430-4
  11.