Characterization of Gastrointestinal Symptom Type and Severity in Parkinson's Disease: A Case–Control Study in an Australian Cohort

Abstract

BackgroundWhile constipation is a well‐known non‐motor symptom which may precede the onset of the classical motor symptoms of PD, there have been few comprehensive studies of gastrointestinal (GI) symptoms in people with PD (PwP).ObjectivesTo investigate the spectrum of GI symptoms in an Australian PwP cohort and their relationship to use of anti‐parkinsonian medications dietary habits and smoking.MethodsThe prevalence and severity of GI symptoms were compared in a group of 163 PwP and 113 healthy control subjects using the Gastrointestinal Symptom Rating Scale (GSRS). Corrected linear regression models were used to determine differences between PwP and controls, and to investigate the influence of different classes of anti‐Parkinsonian medications.ResultsPwP reported a greater frequency of constipation and GI‐associated illnesses when compared to healthy controls. Total GSRS scores (P < 0.0001), upper GI symptoms (P < 0.0001), and hypoactive GI Symptoms (P < 0.0001) were all significantly greater in the PD cohort than controls. Further analyses revealed a positive association between the use of anti‐Parkinsonian medications and total GSRS scores (P < 0.001), as well as upper GI symptoms (P < 0.001) and hypoactive GI function (P < 0.001).ConclusionsThis study illustrates the frequency and array of GI symptoms in a large PD cohort. The findings indicate that anti‐parkinsonian medications play an important role in the presentation and development of GI symptoms.

Changes in the Gut Microbiome and Predicted Functional Metabolic Effects in an Australian Parkinson’s Disease Cohort

“…Bile acids eliminate cholesterol from the body (Ticho et al, 2019), aid GI motility (Ticho et al, 2019), and reduce the bacteria found in the small intestine (Ridlon et al, 2014). This corresponds with previous research indicating constipation as one of the first symptoms in PD and identifying that PwP are more likely to be constipated than the general public (Kenna et al, 2021). Another interesting implication of this finding would help explain the increased prevalence of small intestinal bacterial overgrowth (SIBO) in PwP, as the reduced biosynthesis of bile acids would diminish the capacity to moderate bacterial populations in the small intestine.…”

“…Furthermore, butyrate also regulates the permeability of the gut through the stimulation of tight junctions and mucus production (Getachew et al, 2020), and promotes an acidic gut pH which reduces the growth of pathogenic pro-inflammatory bacteria (Walker et al, 2005). The reduction in Agathobaculum, which exhibits effects on gut motility regulating ability, could be a contributory factor to the increased severity and frequency of GI dysmotility symptoms in this particular cohort (Kenna et al, 2021), as well as other PwP cohorts (Kaye et al, 2006;Knudsen et al, 2017;Li et al, 2019;Cirstea et al, 2020). On the other hand, Gammaproteobacteria, a pro-inflammatory bacterium that produces endotoxins and is associated with GI disorders such as Crohn's disease (Sekido et al, 2020), and Synergistetes (Synergistia) a bacterium involved in GI infections (Vartoukian et al, 2007), were significantly increased in our PwP cohort.…”

“…A detailed history of gastrointestinal disorders; diet content; and antibiotic, probiotic, prebiotic, antacid or constipation treatment use within the previous year was obtained (Table 1). All study participants also completed a validated 15-question Gastrointestinal Symptom Rating Scale (GSRS) to evaluate the frequency and severity of gastrointestinal symptoms, as previously described (Kenna et al, 2021). All PwP were assessed in the "ON" state using the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, and the Hoehn and Yahr scale, with a higher score and stage representing greater disease severity.…”

Parkinson' disease medication alters rat small intestinal motility and microbiota composition

“…Small intestinal motility is one of the factors influencing SIBO 40 , and is prevalent in PD patients. [41][42][43] PD medication has been also shown to be associated with GI symptoms 44 and reduced transit times. 45 Here, we show that the PD medication per se, in healthy rats, affect the microbial profile, besides its effect on gut motility (Figure 3).…”

“…40 SIBO is prevalent (up to 54•5 %) and significantly higher in PD patients. [41][42][43] Recently, PD medication has been also associated with the development of GI-symptoms 44 or GI-transit 45 in PD patients. Analogously, we showed that the unabsorbed residues of levodopa that reach the distal small intestine is converted to a bioactive molecule, which reduces ileal contractility in mice ex vivo.…”