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Microbiota and the Predictive Adaptive Response

Developmental programming is thought to be a source of many adult diseases, including obesity, diabetes, and cardiovascular disease. The notion that early life experiences, including nutrient transfer from the mother in utero, can shape the risk of later adult diseases has been termed the “predictive adaptive response”.

This relationship first came to light when Barker documented a curious association between birth weight and adult cardiac events in British men. Babies born small had a higher risk of chronic inflammatory diseases as adults. These small babies have been described as adopting a “thrifty phenotype.” That is, nutrient deprivation as a fetus is thought to have shaped the developmental trajectory in these individuals. This shift results in reduced expenditure on muscle and increased energy storage as fat. These developmental adjustments would be “thrifty” because muscle has much greater metabolic fuel demands than does fat. In addition, these small babies are also known to differ in the composition of their adipose tissues: they store fat primarily as visceral fat.  Visceral fat is the “unhealthy” abdominal fat which predisposes to diabetes and atherosclerosis. However, visceral fat has the advantage of being readily mobilized in the setting of stress or infection. The combination of metabolic thriftiness, reduced outlays devoted to costly muscle tissue, and increased ability to mobilize energy during times of stress is posited to promote survival. In terms of human development, the thrifty phenotype also preserves priority energy access for key organs, such as the brain.  For an expanded treatment of these concepts, see Kuzawa et al: Developmental Origins of Adult Function and Health: Evolutionary Hypotheses

As a corollary to these arguments, it has been suggested that fetal nutrient provisioning provides a signal to the developing organism about the future state of the environment it will be born into. If conditions are good, reflected by increased maternal transfer of resources to the developing fetus, the baby will be born large. If these cues are an accurate signal of plentiful nutrition in childhood and later life, babies born large may develop as more muscular, larger, and with less stored fat, even though this strategy may be riskier in times of famine or epidemic disease.  By contrast, small babies, reflecting poor maternal nutrient provisioning in utero, may portend a resource-scarce environment during childhood and early adulthood. These infants might have an advantage if they develop a thrify phenotype that promotes a robust response to environmental stress.   The key is whether in utero conditions can predict a future state. If so, these fetal physiological adjustments, favoring a thrifty phenotype, will be adaptive in later life.

Recently, the Predictive Adaptive Response (PAR), which provides the underpinnings of the adaptive nature of the thrifty phenotype, has come under criticism. The main argument against the PAR is that fetal nutrient scarcity is a poor predictor of later scarcity. Even if a mother is pregnant in a time of famine, it does not mean that 20 years later, their adult offspring will be more likely to experience famine than a baby born to a mother who did not experience food shortage. As a result the thrifty phenotype is as likely to be maladaptive in adulthood than adaptive.

However, the fetus does have access to other cue which are an excellent predictor of a future state.

These are microbial cues, because infants inherit their microbiota from their mothers. Because microbiota transfer is a key determinant of the composition of the gut microbiota, with durable effects, it follows that microbiota transfer offers a method of intergenerational transfer of phenotype.

With that it mind, maybe it is time propose that we rename the predictive adaptive response to the “microbial predictive adapative response”.

The developing fetus is bombarded with cues of microbial environment of its mother, both before and after birth, These microbiota will become the core microbiome, part of which may stay with the individual for life.

It turns out that exposure to certain microbes triggers immune responses that tunes the immune system to deal with those future infectious threats from within and without.  Transfer of microbiota, from maternal skin, breast milk, GI tract, and saliva, play a huge role in determining whether an infant has allergic diseases, metabolic disorders, and autoimmune diseases.

From Nature Reviews 2012:

Title: Microbial contact during pregnancy, intestinal colonization and human disease

Samuli Rautava, Raakel Luoto, Seppo Salminen and Erika Isolauri
Abstract | Interaction with colonizing intestinal bacteria is essential for healthy intestinal and immunological development in infancy. Advances in understanding early host–microbe interactions indicate that this early microbial programming begins in utero and is substantially modulated by mode of birth, perinatal antibiotics and breastfeeding. Furthermore, it has become evident that this stepwise microbial colonization process, as well as immune and metabolic programming by the microbiota, might have a long-lasting influence
on the risk of not only gastrointestinal disease, but also allergic, autoimmune and metabolic disease, in later life. Modulating early host–microbe interaction by maternal probiotic intervention during pregnancy and breastfeeding offers a promising novel tool to reduce the risk of disease. In this Review, we describe the current body of knowledge regarding perinatal microbial contact, initial intestinal colonization and its association with human disease, as well as means of modulating early host–microbe interaction to reduce the risk of disease in the child.”

Categories: Uncategorized

Joe Alcock

Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine

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