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<p>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 <i>Drosophila</i>. 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.</p>

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Microbiome-emitted scents activate olfactory neuron-independent airway-gut-brain axis to promote host growth in Drosophila

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月4日

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  • Jin-Woo Lee,
  • Kyung-Ah Lee,
  • In-Hwan Jang,
  • Kibum Nam,
  • Sung-Hee Kim,
  • Minsoo Kyung,
  • Kyu-Chan Cho,
  • Ji-hoon Lee,
  • Hyejin You,
  • Eun-Kyoung Kim,
  • Young Hoon Koh,
  • Hansol Lee,
  • Junsun Park,
  • Soo-Yeon Hwang,
  • Youn Wook Chung,
  • Choong-Min Ryu,
  • Youngjoo Kwon,
  • Soung-Hun Roh,
  • Ji-Hwan Ryu,
  • Won-Jae Lee

摘要

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.