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

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.

KEYWORDS:

• Bronchial asthma
• allergic disease
• microbiota
• Scfas
• propionate
• lactation period
• GPR41
• Tlrs
• human birth cohort

Acknowledgments

We thank T. Kato for analysis support. T.I. is supported by the Research Fellowship for Young Scientists.

Disclosure statement

No potential conflict of interest was reported by the authors.

Authors’ contributions

T.I., and H.O. conceived the study. T.I. designed and performed the experiments and analyses, and cowrote the manuscript. Y.N., R.S., N.S-A., T.N., F.Y., and N.S-I. made the CHIBA Study samples possible and accessible. S.S., and T.J. helped with the mouse experiments. W.S. and M.H. performed and analyzed 16S rRNA sequencing. I.K. provided essential materials and helped to interpret the data. H.O. directed the research and cowrote the manuscript.

Ethics approval and consent to participate

All mouse experiments were performed as approved by the Animal Care and Use Committee of the RIKEN Yokohama Campus (Permission number: AEY2022–008) and carried out according to the committee’s guidelines.

All human experiments have been approved by the research ethics committee of the RIKEN Yokohama Campus and Chiba University. Written informed consent was obtained from all participants.

Consent for publication

Written informed consent was obtained from all participants.

Data availability statement

The 16S rRNA sequence data that support the findings of this study are openly available in DDBJ Sequence Read Archive at https://www.ddbj.nig.ac.jp/ddbj/index.html, reference number DRA014484.

The RNA sequence dat that support the findings of this study are openly available in Gene Expression Omnibus at https://www.ncbi.nlm.nih.gov/geo/, reference number GSE207711.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2206507

Additional information

Funding

This work was supported in part by grant from Japan Society for the Promotion of Science at https://www.jsps.go.jp/english/e-grants/: Grants-in-Aid for Young Scientists (19K17690 to T.I.), The Japan Agency for Medical Research and Development at https://www.amed.go.jp/en/index.html: AMED (16ek0410029h0001 to N.S.), and The Japan Agency for Medical Research and Development at https://www.amed.go.jp/en/index.html: AMED-CREST (19gm0710009h0006 to H.O.)