Breast Milk and Microbiota in the Premature Gut: A Method of Preventing Necrotizing Enterocolitis

Summary

Necrotizing enterocolitis (NEC) is an inflammatory condition of the gastrointestinal tract that affects approximately 10% of newborn infants <1,500 g. It occurs in part due to colonizing bacteria interacting with an immature intestine [1]. The immature intestine evokes an innate immune response with increased TLR-4 expression on its intestinal surface and increased signal molecule and NF-κB levels in enterocytes combined with decreased levels of regulatory molecules (e.g., SIGIRR, IRAK-M, and A20). This results in an inflammatory response rather than immune homeostasis [2].

To counteract this tendency, neonatologists have supported breast milk donation [3]. They have also used a variety of probiotics [4]. A combination of both factors – breast milk and probiotics (symbiosis) – appears to set the best results. Therefore, the mechanism of this effect on newborn infants has attracted increased interest [5].
We have shown that Bifidobacterium infantis and breast milk produce a molecule which is effective against NEC. This molecule has been shown to affect inflammation in the immature intestine by inhibiting the transcription factor aryl hydrocarbon (AHR) which stimulates IL-8 production (Fig. 1).

In addition, complex carbohydrates in breast milk interacting with colonizing bacteria such as B. infantis can produce short-chain fatty acids (SCFAs) which are able to induce anti-inflammatory effects via G-coupled receptor (GRP 109) and modulate inflammatory responses of immature enterocytes (Fig. 2).

Fixed protocols in clinical trials including a large number of infants are required to confirm the significance of these effects on the newborn intestine regarding NEC prevention and thus to provide a way to prevent NEC in premature infants.




References
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