Introduction: The relationship between the brain, gut and bladder is complex. To aid further studies to understand the relationship between specific stressors and mental health disorders (MHD), intestinal sequelae and lower urinary tract symptoms (LUTS) we aim to identify potential mechanisms and biological processes that explain brain-gut-bladder associations in women. Methods: Identification of mechanisms followed guidelines of conceptual model development. Results: Traumatic events, chronic stressors and MHD may lead to a maladaptive stress response with implications for communication and signaling between the brain, gut and bladder. Figure 1 depicts three bidirectional axes; the gut, brain and bladder are key actors engaged in “communication” across the life course. Each organ function is guided by key inputs that ideally assist in maintaining health but also can initiate or exacerbate dysfunction. The gut can communicate with the brain and bladder in ways that shape trajectories of MHD, neuropsychological resilience, central physiological dysregulation and the likelihood of developing and experiencing persistent LUTS. Psychological stressors influence communication between the gut and the brain with accompanying alterations in gut metabolites, neurotransmitters and microbiota. Gut bacteria produce molecules and metabolites that alter production of neurotransmitters (serotonin, dopamine), amino acids (tryptophan), short chain fatty acids (butyrate, acetate) and amyloid proteins that influence the brain (neuronal, blood, immune pathways), thus mediating communication between the gut and brain. Gut bacteria also alter inflammatory immune response via endotoxins, conferring vulnerability or resistance to bladder infections. Microbiota signal neurogenesis, microglia maturation and synaptic pruning; they also calibrate brain-gut-bladder axis communication through neurotransmission, synaptogenesis & the vagus nerve. Conclusions: Some neurotransmitter alterations seen with stress may not be caused directly by perceptions of stress, but rather by stress-related alteration in intestinal bacteria. The brain-gut-bladder axis has implications for research as well as novel prevention and treatment approaches. An intriguing area for research is how the microbiome may influence the brain & bladder. SOURCE OF Funding: The Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium is supported by the National Institutes of Health (NIH) through cooperative agreements (grants U24DK106786, U01DK106853, U01DK106858, U01DK106898, U01DK106893, U01DK106827, U01DK106908, U01DK106892, U01DK126045).