Microbiome-emitted scents activate olfactory neuron-independent airway-gut-brain axis to promote host growth in Drosophila
While it is now accepted that the microbiome has strong impacts on animal growth promotion, the exact mechanism has remained elusive. Here we show that microbiome-emitted scents contain volatile somatotrophic factors (VSFs), which promote host growth in an olfaction-independent manner in Drosophila. We found that inhaled VSFs are readily sensed by olfactory receptor 42b non-neuronally expressed in subsets of tracheal airway cells, enteroendocrine cells, and enterocytes. Olfaction-independent sensing of VSFs activates the airway-gut-brain axis by regulating Hippo, FGF and insulin-like growth factor signaling pathways, which are required for airway branching, organ oxygenation and body growth. We found that a mutant microbiome that did not produce (2R,3R)-2,3-butanediol failed to activate the airway-gut-brain axis for host growth. Importantly, forced inhalation of (2R,3R)-2,3-butanediol completely reversed these defects. Our discovery of contact-independent and olfaction-independent airborne interactions between host and microbiome provides a novel perspective on the role of the airway-gut-brain axis in microbiome-controlled host development.
Authors
- Kyu-Chan Cho (ORCID: https://orcid.org/0009-0004-8177-8275)
- Soo‐Yeon Hwang (ORCID: https://orcid.org/0000-0002-8548-5777)
- Hye Jin You (ORCID: https://orcid.org/0000-0001-5566-5171)
- Hansol Lee (ORCID: https://orcid.org/0000-0001-8725-3710)
- Minsoo Kyung
- Ji-Hwan Ryu (ORCID: https://orcid.org/0000-0001-6969-7465)
- Eun Kyoung Kim (ORCID: https://orcid.org/0000-0002-7653-3503)
- Young Hoon Koh (ORCID: https://orcid.org/0000-0002-8717-6089)
- Choong‐Min Ryu (ORCID: https://orcid.org/0000-0002-7276-1189)
- Youngjoo Kwon (ORCID: https://orcid.org/0000-0001-6256-3042)
- Youn Wook Chung (ORCID: https://orcid.org/0000-0002-4382-1410)
- Soung‐Hun Roh (ORCID: https://orcid.org/0000-0003-3851-7200)
- Junsun Park (ORCID: https://orcid.org/0000-0002-7569-7653)
- Ki-Bum Nam
- Jin Woo Lee (ORCID: https://orcid.org/0000-0003-4245-9381)
- Jihoon Lee (ORCID: https://orcid.org/0000-0001-5327-824X)
- Won‐Jae Lee (ORCID: https://orcid.org/0000-0002-1438-8005)
- Sunghee Kim (ORCID: https://orcid.org/0009-0000-0091-5591)
- In-Hwan Jang
- Kyung-Ah Lee
Institutions
- Ewha Womans University (KR)
- Seoul National University (KR)
- Yonsei University (KR)
- Biosolution (South Korea) (KR)
- National University College (PR)
- Institute of Molecular Biology (AM)
- Korean College of Helicobacter and Upper Gastrointestinal Research (KR)
- Korea Research Institute of Bioscience and Biotechnology (KR)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-04
- DOI
- https://doi.org/10.1038/s41467-025-57484-4
- Citations
- 8
- Primary Topic
- Invertebrate Immune Response Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 6.38
Funders
- National Research Foundation of Korea