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

作者：Jin Woo Lee, Kyung-Ah Lee, In-Hwan Jang, Ki-Bum Nam, Sunghee Kim, Minsoo Kyung, Kyu-Chan Cho, Ji-hoon Lee, Hye Jin 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 · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-57484-4 · 被引用次数：9 · 研究领域：Invertebrate Immune Response Mechanisms、Insect symbiosis and bacterial influences、Neurobiology and Insect Physiology Research

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. Animals detect microbiomes through smell, aiding communication, group recognition, and behavior. Here with Drosophila model, the authors show that airway and gut cells can sense microbiome-emitted scents independently of smell, promoting host growth.