Attraction to secreted isoamyl alcohol as a signal for beneficial commensals

C. elegans, a bacterivore living in microbially-complex environments, harbors a characteristic community of gut bacteria that contribute to its health and fitness. What determines which environmental bacteria end up as commensals is largely unknown in C. elegans, as in other animals. Previous work found that gut Pantoea isolates supported rapid worm development and infection resistance, while environmental congenerics were inferior. Notably, worms were preferentially attracted to the more beneficial gut isolates. Using bioactivity-guided fractionation and gas chromatography-mass spectrometry analysis, we identified bacterially derived isoamyl alcohol (IAA) as a secreted volatile attractant underlying this preference. Screening of worm mutants implicated AWC sensory neuron-associated genes in preferential attraction to beneficial Pantoea and established a causal link between IAA sensing and colonization by beneficial strains. While IAA sensing was important for initial colonization, gut-associated Pantoea strains ultimately outcompeted environmental congenerics over time, indicating that microbiome assembly is shaped by two complementary processes: host behavioral preference for high-IAA producers and bacterial competitive fitness within the gut. While IAA is a product of leucine metabolism and may function as a nutritional cue, we found that it could also directly enhance host infection resistance, suggesting an additional role in modulating host physiology. Finally, knockout analysis identified a bacterial branched-chain amino acid aminotransferase homolog as important for IAA production. Together, these findings identify bacterial volatile sensing as an important and underexplored mechanism shaping microbiome composition and its contributions to host fitness.