The propionate-GPR41 axis in infancy protects from subsequent bronchial asthma onset

婴儿时期的丙酸-GPR41 轴可预防随后的支气管哮喘发作

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作者:Takashi Ito, Yumiko Nakanishi, Ryohei Shibata, Noriko Sato, Toshi Jinnohara, Sayo Suzuki, Wataru Suda, Masahira Hattori, Ikuo Kimura, Taiji Nakano, Fumiya Yamaide, Naoki Shimojo, Hiroshi Ohno

Abstract

Evidence has accumulated that gut microbiota and its metabolites, in particular the short-chain fatty acid propionate, are significant contributors to the pathogenesis of a variety of diseases. However, little is known regarding its impact on pediatric bronchial asthma, one of the most common allergic diseases in childhood. This study aimed to elucidate whether, and if so how, intestinal propionate during lactation is involved in the development of bronchial asthma. We found that propionate intake through breast milk during the lactation period resulted in a significant reduction of airway inflammation in the offspring in a murine house dust mite-induced asthma model. Moreover, GPR41 was the propionate receptor involved in suppressing this asthmatic phenotype, likely through the upregulation of Toll-like receptors. In translational studies in a human birth cohort, we found that fecal propionate was decreased one month after birth in the group that later developed bronchial asthma. These findings indicate an important role for propionate in regulating immune function to prevent the pathogenesis of bronchial asthma in childhood.

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