Gut Microbiota, Host Gene Experession, and Cell Traffic via Milk

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Summary 

The human neonate is often born with a nonsterile gastrointestinal tract. The mechanism of this in utero colonization is poorly understood, but potential sources include ascending vaginal microbes, transloca- tion of microbes from the maternal intestine or skin, or hematogenous spread from the maternal oral cavity.

Furthermore, human milk is not sterile. Using both culture and non-culture-based techniques, this fluid has been found to be rich in microbes, and they will eventually colonize or at least be present in the intestine of the developing infant with the potential to elicit numerous immune responses via metabolite production, interaction with the
developing infant immune system, and induction of signals for host gene expression.

In addition to the milk microbes, this fluid also provides a source of enzymes such as lipase and alkaline phosphatase. Immunoglobulins, especially IgA, are found at relatively high concentrations. Milk also provides a multitude of biologically active proteins such as lactoferrin and lysozyme. Carbohydrates, including disaccharides such as lactose, when not digested and absorbed by the host can be utilized by microbes that metabolize this sugar to other highly biologically active agents such
as short-chain fatty acids, acetate, propionate, and butyrate. Oligosaccharides serve as nutrients for certain microbes that flourish in their presence and have the ability to interact with the intestinal mucosa of the host.

The cellular composition (including immune cells and stem cells) and siRNAs found in milk exosomes also appear to play important roles in terms of immunologic protection, immune modulation, and transcriptional regulation.

Although exciting, much of the information currently available is associational. These agents are present in milk; we have theories about their roles, without a strong body of mechanistic data. We have also the impression that just because they are present in human milk, they provide specific advantages to the infant who is not fed these components. However, it is clear that despite major efforts, not all babies will be able to receive and benefit directly from their own mothers’ milk. A better understanding not only of the composition of human milk – but also the mechanisms of how these components affect the host – should help us optimize milk for a larger number of infants.

Suggested Reading
Ardissone N, de la Cruz DM, Davis-Richardson AG, et al: Meconium microbiome analysis identifies bacteria correlated with premature birth. PLoS One 2014;9:e90784.

Cacho NT, Lawrence RM: Innate immunity and breast milk. Front Immunol 2017;8:584. Gomez-Gallego C, Garcia-Mantrana I, Salminen S, Collado MC: The human milk microbiome and factors influencing its composition and activity. Semin Fetal Neonatal Med 2016;21:400–405.

Hassiotou F, Geddes DT, Hartmann PE: Cells in human milk: state of the science. J Hum Lact 2013;29:171–182.

Rogier EW, Frantz AL, Bruno ME, et al: Lessons from mother: long-term impact of anti- bodies in breast milk on the gut microbiota and intestinal immune system of breast-
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Josef Neu

Josef Neu

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