SEARCHCOHORTpediatrics, immunology

cohort·pediatrics, immunology, pulmonology, preclinical research, epidemiology·PMC10158560

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

Gut Microbes · 13 authors, 9 centres

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TL;DR

In a mouse model, propionate administration during lactation reduced airway inflammation, an effect mediated by the GPR41 receptor on eosinophils. In a human birth cohort, lower fecal propionate levels at one month of age were observed in children who later developed asthma.

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This study combines a preclinical mouse model with a human birth cohort to investigate the role of the gut microbial metabolite propionate in bronchial asthma. In the mouse model, propionate intake during lactation attenuated eosinophilic airway inflammation and Th2 cytokine production in adult offspring, mediated via GPR41 on eosinophils and associated with upregulation of TLR2, TLR8, and/or TLR9. In a human birth cohort, longitudinal analysis of fecal samples showed that propionate concentrations were decreased at one month of age in children who subsequently developed asthma. The study suggests a protective role for the propionate-GPR41 pathway during early life. The results imply a potential preventive target for asthma but require further validation.

STUDY TYPE

cohort

SPECIALTY

pediatrics

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ORIGINAL PAPER

PMC10158560

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

Gut Microbes

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ABSTRACT

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.

CITATION EXPORT

Takashi Ito, Yumiko Nakanishi, Ryohei Shibata et al.. The propionate-GPR41 axis in infancy protects from subsequent bronchial asthma onset. Gut Microbes. (2023). https://doi.org/10.1080/19490976.2023.2206507

AUTHORS

13 · 9 CENTRES

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

aLaboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
bDepartment of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
cDepartment of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan
dLaboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
eDepartment of Signal Transductions, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
fDepartment of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan
gCenter for Preventive Medical Sciences, Chiba University, Chiba, Japan
hLaboratory for Immune Regulation, Graduate School of Medical and Pharmaceutical Sciences, Chiba University, Chiba, Japan
iImmunobiology Laboratory, Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan