Monday, March 16, 2015

Like Genes, Our Microbes Pass from Parent to Child

Modern assaults on the human microbiome may deprive some infants of coevolved microorganisms that shape their immune systems as well as lead to other developmental problems


Feb 17, 2015 | |

The mountains of genomic-sequencing data generated by the National Institutes of Health's Human Microbiome Project and recent studies provide strong evidence that just as our human genes were transmitted vertically from our parents and from their parents, and ultimately from our distant primate ancestors, the same holds true for our microbial genes.


This intergenerational transfer begins at the moment of birth, when the minimally colonized fetus is exposed to the microbes in its mother’s vagina as it transits out through the birth canal. The infant, covered with Mom’s microbes, swallows some, which become the founders of the intestinal populations. Babies also inoculate Mom’s breast with their new mouth microbes, and she delivers them back, along with constituents in her milk that specifically favor the ancestral microbes. Thus, Mom’s skin and mouth are other important sources of baby’s early microbes.


Over the course of early childhood the diversity of microbes in and on the baby grows, and by the age of three years it is relatively adultlike. Those first three years, when the microbiome is developing and is most dynamic, are also when the baby’s metabolism, immunity and cognition develop. The stages of a child’s physical and mental development are subject to highly evolved patterns and constraints, and animal experiments suggest that the same holds true for the succession of microbes and the early-life assembly of gut microbiota.


Here is where the trouble begins: by its very nature, the process by which the gut microbiome is shaped involves plasticity. Yet there must be boundaries—and what happens when these are crossed? To what extent is the microbiome vulnerable to perturbation? It is obvious that strong threats may delay normal microbial succession, but they also might lead to extinction of particular taxa. Because both the timing and composition of the successional process and players may be important these disturbances have the potential to change the arc of development of the microbiota and the baby.


What kinds of threats could there be? Because the critical issue is the intergenerational transfer of microbes and its timed assembly, three periods are relevant: before pregnancy, during pregnancy and in the child's early life. For all three periods, antibiotic use is relevant because it may directly change maternal microbes prior to transfer or the child’s microbes afterward. Elective cesarean sections mean that the child misses the birth canal transit, and antibacterials in soaps and foods directly affect microbiota composition. Infant formulas have not been constructed with the benefit of millions of years of mammalian evolution, because breast milk contains nutrients that specifically select for the growth of preferred coevolved organisms and inhibit opportunists and pathogens.


The aggregate of modern assaults on the early-life microbiome suggests that our progeny may not be inheriting their fair share. Exceeding the developing microbiome’s plasticity predictably leads to consequences, as growing evidence evinces. Studies have linked C-sections and exposures to prenatal and postnatal antibiotics to increased risk of obesity, diabetes, celiac disease, asthma and allergies, among other ailments that have their roots in development. This is especially problematic because these exposures are so highly prevalent. We now must assess how to effectively restore our lost microbiomic heritage.


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