Microbial metabolites as engines of behavioral variation across animals.

The microbiome, especially that present in the gut, has emerged as a key modulator of animal behavior. However, the extent of its influence across species and behavioral repertoires, as well as the underlying mechanisms, remains poorly understood. Increasing evidence suggests that microbial metabolites play an important role in driving behavioral variation. In this review, we synthesize findings from vertebrates to invertebrates, spanning both model and non-model organisms, to define key groups of microbial-derived metabolites involved in modulating seven distinct behaviors: nutrition, olfaction, circadian rhythms, reproduction, locomotion, aggression, and social interactions. We discuss how these microbial metabolites interact with host chemosensory systems, neurotransmitter signaling, and epigenetic modifications to shape behavior. Additionally, we highlight critical gaps in mechanistic understanding, including the need to map additional host receptors and signaling pathways, as well as the untapped potential of microbial biosynthetic gene clusters as sources for novel bioactive compounds. Advancing these areas will enhance understanding of the microbiome's role in behavioral modulation and open new avenues for microbiome-based interventions for behavioral disorders.