The infant gut bacterial microbiota and risk of pediatric asthma and allergic diseases

Abstract

Among the many areas being revolutionized by the recent introduction of culture independent microbial identification techniques is investigation of the relationship between close contact with large animals, antibiotics, breast feeding, mode of birth, and other exposures during infancy as related to a reduced risk of asthma and allergic disease. These exposures were originally clustered under the “Hygiene Hypothesis” which has morphed into the “Microbiota Hypothesis”. This review begins by summarizing epidemiologic studies suggesting that the common feature of these allergy risk-related exposures is their influence on the founding and early development of a child's gut microbiota. Next studies using culture independent techniques are presented showing that the microbiota of children who have experienced the exposures of interest have altered gut microbiota. Finally, selected mouse and human studies are presented which begin to corroborate the protective exposures identified in epidemiologic studies by identifying mechanisms through which microbes can alter immune development and function. These microbially driven immune alterations demonstrate that microbial exposures in many cases could alter the risk of subsequent allergic disease and asthma. Hopefully a better understanding of how microbes influence allergic disease will lead to safe and effective methods for reducing the prevalence of all forms of allergic disease.

Dog introduction alters the home dust microbiota

“…These results should be viewed as further evidence in support of the evolving “Microbiota Hypothesis” related to allergy and asthma risk . The hypothesis is that the environmental microbial diversity influences the assemblage process of an infant's gut microbiota ecosystem which subsequently, in partnership with exposure to allergens and microbes, influences the child's immune development and risk for allergies and asthma . Evidence supporting this hypothesis continues to increase.…”

Remote Sensing Between Liver and Intestine: Importance of Microbial Metabolites

“…During development, the “Hygiene Hypothesis” states that newborns that are delivered by caesarian section or raised in an overly clean environment are more susceptible to pediatric asthma and allergic diseases. Epidemiologic studies have suggested that the common feature of the increases risk of allergy is at least partially due to the perturbation in the founding and early development of a child’s gut microbiota (125). Conversely, allergic airway inflammation can reduce gut microbial diversity, whereas D-tryptophan produced from probiotic supplement does the opposite (126).…”

Strategies to alter the natural history of childhood asthma

“…Culture-independent high-throughput methods have revolutionized the identification and quantification of genetic material, and knowledge has rapidly accumulated regarding the microbial composition of human living environments and bodies [68*,69]. These developments occurred concomitantly with the proposal and evolution of the “hygiene hypothesis,” which posits that reduced microbial exposure accounts for the rising prevalence of allergic disease [70].…”

“…The hygiene hypothesis is based on the now well-documented finding that risk of allergic disease is reduced in association with a variety of environmental exposures, among which household size was the first to be identified [68*,69,70]. Wu and colleagues recently showed that exposures in early infancy may be particularly important [71*].…”

“…As many of the same exposures that are linked to reduced risk of allergy have come to be recognized as determinants of human microbial composition, including residence on a farm, cohabitation with a dog, day care attendance, and vaginal birth, the hygiene hypothesis has evolved into a “microbiota hypothesis” in which environmental factors reduce allergic disease via modification of the host microbiome [68*,69,72*]. Other recognized asthma risk factors may also act via perturbations of the human microbiome.…”