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1.
Allergy ; 74(11): 2103-2115, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30964945

RESUMO

Imbalance, or dysbiosis, of the gut microbiome of infants has been linked to an increased risk of asthma and allergic diseases. Most studies to date have provided a wealth of data showing correlations between early-life risk factors for disease and changes in the structure of the gut microbiome that disrupt normal immunoregulation. These studies have typically focused on one specific risk factor, such as mode of delivery or early-life antibiotic use. Such "micro-level" exposures have a considerable impact on affected individuals but not necessarily the whole population. In this review, we place these mechanisms under a larger lens that takes into account the influence of upstream "macro-level" environmental factors such as air pollution and the built environment. While these exposures likely have a smaller impact on the microbiome at an individual level, their ubiquitous nature confers them with a large influence at the population level. We focus on features of the indoor and outdoor human-made environment, their microbiomes and the research challenges inherent in integrating the built environment microbiomes with the early-life gut microbiome. We argue that an exposome perspective integrating internal and external microbiomes with macro-level environmental factors can provide a more comprehensive framework to define how environmental exposures can shape the gut microbiome and influence the development of allergic disease.


Assuntos
Asma/etiologia , Suscetibilidade a Doenças , Exposição Ambiental , Microbioma Gastrointestinal , Interações Hospedeiro-Patógeno , Hipersensibilidade/etiologia , Fatores Etários , Animais , Suscetibilidade a Doenças/imunologia , Humanos , Imunomodulação , Microbiota
2.
Elife ; 102021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33876729

RESUMO

Bacterial members of the infant gut microbiota and bacterial-derived short-chain fatty acids (SCFAs) have been shown to be protective against childhood asthma, but a role for the fungal microbiota in asthma etiology remains poorly defined. We recently reported an association between overgrowth of the yeast Pichia kudriavzevii in the gut microbiota of Ecuadorian infants and increased asthma risk. In the present study, we replicated these findings in Canadian infants and investigated a causal association between early life gut fungal dysbiosis and later allergic airway disease (AAD). In a mouse model, we demonstrate that overgrowth of P. kudriavzevii within the neonatal gut exacerbates features of type-2 and -17 inflammation during AAD later in life. We further show that P. kudriavzevii growth and adherence to gut epithelial cells are altered by SCFAs. Collectively, our results underscore the potential for leveraging inter-kingdom interactions when designing putative microbiota-based asthma therapeutics.


Assuntos
Asma/microbiologia , Microbioma Gastrointestinal/fisiologia , Pichia/fisiologia , Animais , Bactérias , Fenômenos Fisiológicos Bacterianos , Estudos de Casos e Controles , Criança , Pré-Escolar , Humanos , Lactente , Camundongos Endogâmicos C57BL , Organismos Livres de Patógenos Específicos
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