Breastfeeding in Neonatal Bacterial Colonization

2022 11 Projects FLRF

The Role of Breastfeeding in Neonatal Bacterial Colonization project took place at the Mucosal Immunology and Biology Research Center (MIBRC) at Massachusetts General Hospital – a major teaching hospital of Harvard Medical School. 

Led by Professor W. Allan Walker and his team at MIBRC and supported by FLRF, the project investigated the protective mechanisms of breastmilk during the newborn period. Its aim was to reduce the number of children affected by inflammatory allergic and chronic diseases caused by unbalanced colonization of infants’ intestines.

The study followed the hypothesis that breastmilk provides a protective link from mother to newborn in the extrauterine environment by stimulating a symbiotic, initial intestine colonization, leading to intestinal immune homeostasis and a reduction of the intestinal inflammation that causes immune-mediated diseases.

Over the first year of the project, Professor Walker and his team established the importance of nutrients in breastmilk (complex carbohydrates and tryptophan) interacting with either breastmilk microbiota or microbiota in the infant gut, stimulated by exclusive breastfeeding. In two submitted manuscripts, they showed that breastmilk-induced microbiota, e.g., “pioneer” bacteria, can metabolize breastmilk nutrients for protective functionality. They also identified indole-lactic acid (ILA), a metabolic product of breastmilk tryptophan interacting with Bifidobateria infantis (a “pioneer” bacterium); ILA inhibits the excessive inflammation seen with colonization in the newborn intestine and may be an important protective factor when mother’s expressed breastmilk is fed to her premature infant to protect against necrotizing enterocolitis.

These research findings could have a direct, long-lasting impact on current feeding practices, especially in the neonatal intensive care unit, and could lead to better acceptance and understanding of the importance of breastmilk in general.

Huang W, Cho KY, Meng D, Walker WA. The impact of indole-3-lactic acid on immature intestinal innate immunity and development: a transcriptomic analysis. Sci Rep. 2021;11(1):8088. DOI: 10.1038/s41598-021-87353-1

Gao Y, Davis B, Zhu W, Zheng N, Meng D, Walker WA. Short-chain fatty acid butyrate, a breast milk metabolite, enhances immature intestinal barrier function genes in response to inflammation in vitro and in vivo. Am J Physiol Gastrointest Liver Physiol. 2021;320(4):G521–30. DOI: 10.1152/ajpgi.00279.2020

Zheng N, Gao Y, Zhu W, Meng D, Walker WA. Short chain fatty acids produced by colonizing intestinal commensal bacterial interaction with expressed breast milk are anti-inflammatory in human immature enterocytes. PLoS One. 2020;15(2):e0229283. DOI: 10.1371/journal.pone.0229283

Meng D, Sommella E, Salviati E, Campiglia P, Ganguli K, Djebali K et al. Indole-3-lactic acid, a metabolite of tryptophan, secreted by Bifidobacterium longum subspecies infantis is anti-inflammatory in the immature intestine. Pediatr Res. 2020 Jan 16. DOI: 10.1038/s41390-019-0740-x. [Epub ahead of print]

Senger S, Ingano L, Freire R, Anselmo A, Zhu W, R Sadreyev et al. Human fetal-derived enterospheres provide insights on intestinal development and a novel model to study Necrotizing Enterocolitis (NEC). Cell Mol Gastroenterol Hepatol. 2018 Jan 31;5(4):549-568. DOI: 10.1016/j.jcmgh.2018.01.014. eCollection 2018.

Jiang F*, Meng D*, Zhu W, Weng M, Kasper DL, Walker WA. The symbiotic bacterial surface factor polysaccharide A on bacteroides fragilis Inhibits IL-1 β-induced inflammation in human fetal enterocytes via toll receptors 2 and 4. Plos One. 2017;12(3):e0172738. DOI: 10.1371/journal.pone.0172738. eCollection 2017. (*shared authorship)

Gregory KE*, Samuel BS*, Houghteling P, Shan G, Ausubel FM, Sadreyev RI et al. Influence of maternal breast milk ingestion on acquisition of the intestinal microbiome in preterm infants. Microbiome. 2016;4(1):68. DOI: 10.1186/s40168-016-0214-x. (*shared authorship)

Walker WA, Iyengar RS. Breast milk, microbiota and intestinal immune homeostasis. Pediatr Res. 2014;77(1-2):220-228. DOI: 10.1038/pr.2014.160. Epub 2014 Oct 13.

Jeurink PV, van Bergenhenegouwen J, Jiménez E, Knippels LM, Fernández L, Garssen J et al. Human milk: a source of more life than we imagine. Benef Microbes. 2013;4(1):17-30. DOI: 10.3920/BM2012.0040.

Chichlowski M, De Lartigue G, German JB, Raybould HE, Mills DA. Bifidobacteria isolated from infants and cultured on human milk oligosaccharides affect intestinal epithelial function. J Pediatr Gastroenterol Nutr. 2012;55(3):321-327. DOI: 10.1097/MPG.0b013e31824fb899.

Schwartz S, Friedberg I, Ivanov IV, Davidson LA, Goldsby JS, Dahl DB et al. A metagenomic study of diet dependent interaction between gut microbiota and host in infants reveals differences in immune response. Genome Biol. 2012;13(4):R32. DOI: 10.1186/gb-2012-13-4-r32.

Rautava S, Walker WA. Academy of Breastfeeding Medicine founder’s lecture 2008: Breastfeeding – An extrauterine link between mother and child. Breastfeed Med. 2009;4(1):3-10. DOI: 10.1089/bfm.2009.0004.

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