Evaluation of bidirectional gut-brain axis and anorectal function in Parkinson's disease with constipation

Background: Parkinson's disease (PD) is a neurodegenerative movement disorder with prodromal and highly prevalent gastrointestinal (GI) symptoms, especially constipation. Although PD models suggest gut-brain axis dysfunction, the mechanistic underpinnings and their correlation with GI symptoms are poorly understood. Aim: To examine the bidirectional gut-brain axis function in PD and correlate it with constipation severity, PD duration, and severity. Methods: Rectal sensory thresholds and afferent cortical evoked potentials (CEP) were assessed using a 4-ring EMG electrode probe. Efferent anal and rectal motor evoked potentials (MEPs) were obtained following transcranial and lumbosacral magnetic stimulation. Bowel symptoms were assessed by prospective stool diary. The CEP and MEP latencies, rectal sensory thresholds, and anorectal sensorimotor data were compared between PD subjects and age-adjusted healthy subjects. Key Results: Twenty-five PD subjects with constipation (F/M = 6/19) and 20 healthy subjects (F/M = 14/6) were enrolled. The first and pain sensation thresholds were higher in PD subjects than healthy subjects (p < 0.002) but lost significance after adjustment for age. Age-adjusted rectal CEP and right-sided cortico-anal MEP latencies were prolonged in PD subjects compared to healthy subjects (p < 0.04). Also, half (4 of 8) age-adjusted spino-anal and rectal MEP latencies in PD subjects were significantly longer. In multivariate linear analysis, first rectal sensation and right-sided MEP latencies showed moderate correlation with constipation severity. Conclusions & Inferences: Parkinson's disease is associated with significant bidirectional gut-brain axis dysfunction as evidenced by prolonged afferent and efferent neuronal signaling. Constipation severity in PD is correlated to abnormal rectal sensation and lateralized disturbance of efferent brain-gut signaling.