Lee, J.W., Lee, K.A., Jang, I.H., Nam, K., Kim, S.H., Kyung, M., Cho, K.C., Lee, J.H., You, H., Kim, E.K., Koh, Y.H., Lee, H., Park, J., Hwang, S.Y., Chung, Y.W., Ryu, C.M., Kwon, Y., Roh, S.H., Ryu, J.H., Lee, W.J. (2025). Microbiome-emitted scents activate olfactory neuron-independent airway-gut-brain axis to promote host growth in Drosophila.  Nat. Commun. 16(1): 2199.

FBrf0261766

Research paper

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.

PMC11880416 (PMC) (EuropePMC)