Early Life Microbial Exposure and Immunity Training Effects on Asthma Development and Progression (original) (raw)
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Respiratory and Gut Microbiota in Allergy and Asthma
The Central European Journal of Paediatrics
The objective of the study was to assess the potential mechanisms by which the microbiome influences immune responses in allergy and asthma, especially during early childhood and to evaluate the evidence of respiratory and gut microbiota dysbiosis. The development and progression of allergy and asthma may depend on individual susceptibility, allergen exposure, infections, and exposure to indoor and outdoor air pollution. In recent years there has increasingly been an emphasis on the importance of microbiota in the regulation of immune response and the development of atopic diseases, as well as asthma. Commensal microbes are necessary for the induction of a balanced and tolerogenic immune system especially at an early age. An insufficiency of early life exposure to the environmental microbiota necessary for colonization of the gastrointestinal and/or respiratory tracts results in the development of asthma and allergic diseases. On the other hand, disturbed physiological flora in the digestive and respiratory tract also increase the risk for development and progression of asthma and allergy (allergic march). Microbiota in the gut and lungs may influence both the onset and progression of childhood asthma. These microbiota can be modulated by various environmental factors, including the type of delivery, early-life microbial exposures, diet, antibiotics. Conclusion − Intervention regarding airway microbiome, particularly in early life, might be a strategy for prevention or treatment of asthma and allergies. Further investigations are needed to improve our understanding of the role of the microbiome in inflammation, and to clarify the effect of the regulation of lung and gut microbiota and its influence on the prevention or treatment of allergic diseases and asthma.
Infant airway microbiota and topical immune perturbations in the origins of childhood asthma
Nature Communications, 2019
Asthma is believed to arise through early life aberrant immune development in response to environmental exposures that may influence the airway microbiota. Here, we examine the airway microbiota during the first three months of life by 16S rRNA gene amplicon sequencing in the population-based Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC 2010) cohort consisting of 700 children monitored for the development of asthma since birth. Microbial diversity and the relative abundances of Veillonella and Prevotella in the airways at age one month are associated with asthma by age 6 years, both individually and with additional taxa in a multivariable model. Higher relative abundance of these bacteria is furthermore associated with an airway immune profile dominated by reduced TNF-α and IL-1β and increased CCL2 and CCL17, which itself is an independent predictor for asthma. These findings suggest a mechanism of microbiota-immune interactions in early infancy that predisposes to childhood asthma.
Frontiers in immunology, 2017
This review focuses on the current evidence that maternal dietary and gut bacterial exposures during pregnancy influence the developing fetal immune system and subsequent offspring asthma. Part 1 addresses exposure to a farm environment, antibiotics, and prebiotic and probiotic supplementation that together indicate the importance of bacterial experience in immune programming and offspring asthma. Part 2 outlines proposed mechanisms to explain these associations including bacterial exposure of the fetoplacental unit; immunoglobulin-related transplacental transport of gut bacterial components; cytokine signaling producing fetomaternal immune alignment; and immune programming via metabolites produced by gut bacteria. Part 3 focuses on the interplay between diet, gut bacteria, and bacterial metabolites. Maternal diet influences fecal bacterial composition, with dietary microbiota-accessible carbohydrates (MACs) selecting short-chain fatty acid (SCFA)-producing bacteria. Current evidenc...
Microbial manipulation of immune function for asthma prevention: inferences from clinical trials
Proceedings of the American Thoracic Society, 2007
The "hygiene hypothesis" proposes that the increase in allergic diseases in developing countries reflects a decrease in infections during childhood. Cohort studies suggest, however, that the risks of asthma are increased in children who suffer severe illness from a viral respiratory infection in infancy. This apparent inconsistency can be reconciled through consideration of epidemiologic, clinical, and animal studies. The elements of this line of reasoning are that viral infections can predispose to organ-specific expression of allergic sensitization, and that the severity of illness is shaped by the maturity of immune function, which in turn is influenced by previous contact with bacteria and viruses, whether pathogenic or not. Clinical studies of children and interventional studies of animals indeed suggest that the exposure to microbes through the gastrointestinal tract powerfully shapes immune function. Intestinal microbiota differ in infants who later develop allergic...
The maternal microbiome during pregnancy and allergic disease in the offspring
Seminars in immunopathology, 2017
There is substantial epidemiological and mechanistic evidence that the increase in allergic disease and asthma in many parts of the world in part relates to changes in microbial exposures and diet acting via the composition and metabolic products of the intestinal microbiome. The majority of research in this field has focused on the gut microbiome during infancy, but it is increasingly clear that the maternal microbiome during pregnancy also has a key role in preventing an allergy-prone immune phenotype in the offspring. The mechanisms by which the maternal microbiome influences the developing fetal immune system include alignment between the maternal and infant regulatory immune status and transplacental passage of microbial metabolites and IgG. Interplay between microbial stimulatory factors such as lipopolysaccharides and regulatory factors such as short-chain fatty acids may also influence on fetal immune development. However, our understanding of these pathways is at an early s...
ABSTRACTStudies in European and US farming populations have documented major reductions in asthma prevalence in offspring of mothers exposed to microbial breakdown products present in farm dusts and unprocessed foods. This was associated with enhancement of innate immune competence in the offspring. We sought to (i) identify a safe therapeutic that would reproduce these immunomodulatory effects in a murine model, (ii) elucidate underlying mechanism(s)-of-action, and (iii) develop a scientific rationale for progressing this approach to human trials. We demonstrate in mice that maternal treatment during pregnancy with the microbial-derived immunomodulator OM85, which has been used clinically in adults and children in Europe for >30 years for bolstering resistance to infection-associated airways inflammation, markedly reduces the susceptibility of the offspring of treated mothers to development of experimental atopic asthma. We identify bone marrow precursors of the dendritic cell p...
International immunology, 2018
The incidence of allergic diseases, which increased to epidemic proportions in developed countries over the last few decades, has been correlated with altered gut microbiota colonization. Although probiotics may play a critical role on the restoration of gut homeostasis, its efficiency on the control of allergy is controversial. Here we aimed to investigate the effects of probiotic treatment initiated at neonatal or adult ages on the suppression of experimental ovalbumin-induced asthma. Neonatal or adult mice were orally treated with probiotic bacteria and subjected to ovalbumin-induced allergy. Asthma-like symptoms, microbiota composition and frequencies of the total CD4+ and CD4+Foxp3+ regulatory T (Treg) cells were evaluated in both groups. Probiotic administration to neonates, but not to adults, was necessary and sufficient for the absolute prevention of experimental allergen-induced sensitization. The neonatally-acquired tolerance, transferrable to probiotic-untreated adult rec...