Microbial regulation of interoception

Interoceptive pathways communicate between the body and the brain to coordinate behavioral responses to changes in the internal milieu. An important contributor to the internal milieu of the body is the gastrointestinal microbiome. Here, we conceptualize the role of the microbiome and microbiome-derived metabolites in interoceptive processes that enable homeostasis maintenance. We highlight four key features that make the microbiome a valuable sensory source for interoceptive processes: its capacity to engage canonical sensory pathways, dynamic responsiveness to environmental perturbations, diurnal oscillations aligned with host circadian rhythms, and the selective gating of sensory information through the intestinal barrier. We further explore how microbiome-derived sensory information contributes to homeostasis, imparts valence to events and cues, and serves as a substrate for memory. Collectively, we present a framework for understanding interoceptive dysfunction through the lens of microbiome-host interactions.