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  • Review Article
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Functional urological disorders: a sensitized defence response in the bladder–gut–brain axis

Key Points

  • Functional disorders of the urogenital tract overlap and often co-occur with functional disorders of the gastrointestinal tract, suggesting that they represent a spectrum or continuum across organ systems, sharing underlying hypersensitivity

  • Functional disorders often run a chronic course and display considerable treatment resistance, with heterogeneity in treatment response and in what constitutes treatment success or failure

  • Stress experience, recurrent negative social interactions, infections, and related intestinal syndromes or affective conditions might have a role in the development of functional urogenital disorders

  • Urological and related gastrointestinal functional disorders exist as a function of threat as alarm falsification of a sensitized defence system

  • Under-recognition of a complex multimorbidity phenotype, consisting of urological, gastrointestinal, and affective comorbidity, might contribute to treatment resistance in functional disorders

  • Polysyndromatic patients with persisting complaints after appropriate treatment require a collaborative approach — integrating medical and psychosocial elements is necessary in order to deliver individually tailored solutions for any identifiable disease phenotype

Abstract

Functional urological and gastrointestinal disorders are interrelated and characterized by a chronic course and considerable treatment resistance. Urological disorders associated with a sizeable functional effect include overactive bladder (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS), and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Poor treatment outcomes might be attributable to untreated underlying psychological and psychiatric disorders, as the co-occurrence of functional urological and gastrointestinal disorders with mood and anxiety disorders is common. The hypothetical bladder–gut–brain axis (BGBA) is a useful framework under which this interaction can be studied, suggesting that functional disorders represent a sensitized response to earlier threats such as childhood adversity or previous traumatic events, resulting in perceived emotional and bodily distress — the symptoms of functional disorders. Psychological and physical stress pathways might contribute to such alarm falsification, and neuroticism could be a risk factor for the co-occurrence of functional disorders and affective conditions. Additionally, physical threat — either from external sources or internal sources such as infection — might contribute to alarm falsification by influencing body–brain crosstalk on homeostasis and, therefore, affecting mood, cognition, and behaviour. Multidisciplinary research and an integrated care approach is, therefore, required to further elucidate and remediate functional urological and gastrointestinal polymorphic phenotypes.

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Figure 1: The threatening environment and the bladder–gut–brain axis (BGBA).
Figure 2: Timecourse of cumulative threat and the consecutive alarm falsification of defence.

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Leue, C., Kruimel, J., Vrijens, D. et al. Functional urological disorders: a sensitized defence response in the bladder–gut–brain axis. Nat Rev Urol 14, 153–163 (2017). https://doi.org/10.1038/nrurol.2016.227

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