(A) Visceral convergence of bladder and gut sensory pathways mediate organ crosstalk and the bladder-gut-brain axis. Gut dysbiosis in IC may directly influence sensory pathways, or microbial constituents (LPS and peptidoglycan [PG]) and metabolites in circulation can influence pain circuits centrally via microglia. (B) Dysbiosis-associated immune dysregulation may impact IC pathology by altering the inflammatory milieu and thus affect bladder mast cells and/or Hunner’s lesions. (C) Microglia are potential therapeutic targets for IC by use of drugs that act directly or indirectly.