The Latest Articles on Intestines in Parkinson’s Disease

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles on intestines in Parkinson’s disease.

Title: Association of intestinal inflammation and permeability markers with clinical manifestations of Parkinson's disease
Authors: Ines Rajkovaca Latic, Zvonimir Popovic, Katica Mijatovic, Ines Sahinovic, Vlasta Pekic, Domagoj Vucic, Vesna Cosic, Blazenka Miskic, Svetlana Tomic
Type: Research Article

Abstract:

Introduction
Intestinal inflammation and gut microbiota dysbiosis can stimulate degeneration of dopaminergic neurons and development of Parkinson's disease (PD) via the gut-brain axis in certain patients.
Methods
In a case-control study, fecal markers of intestinal inflammation and permeability were measured using the ELISA method in PD patients and healthy controls. Motor and nonmotor symptoms were assessed using the Movement Disorder Society (MDS) Unified PD Rating Scale, Hoehn & Yahr scale, MDS Non-Motor Symptom Scale, Scales for Outcomes in PD - Autonomic Dysfunction, PD Sleep Scale - 2, Montreal Cognitive Assessment, Beck Anxiety Inventory, and Beck Depression Inventory-II. A correlation was established between the intestinal inflammation and permeability markers and PD symptoms.
Results
Higher levels of beta-defensin 2, zonulin and lactoferrin were recorded in PD patients compared to controls. Calprotectin and secretory immunoglobulin A showed no significant differences. Regression analysis indicated the roles of beta-defensin 2 and lactoferrin in predicting PD likelihood. Calprotectin yielded positive correlations with disease duration, depression, motor fluctuations, and gastrointestinal symptoms; beta defensin 2 with thermoregulation; and secretory immunoglobulin A with depression. Secretory immunoglobulin A showed negative correlation with age and age at disease onset, while zonulin showed negative correlation with the MDS Unified PD Rating Scale total score.
Conclusions
Fecal markers differed in PD patients compared to controls and correlated with age, disease duration, and some nonmotor symptoms. Future studies should identify the subgroups of PD patients that are likely to develop intestinal inflammation.
Access this article: https://doi.org/10.1016/j.parkreldis.2024.106948

Title: Consensus practice recommendations for management of gastrointestinal dysfunction in Parkinson disease.
Authors: Delaram Safarpour, Natividad Stover, David R. Shprecher, Ali G. Hamedani, Ronald F. Pfeiffer, Henry P. Parkman, Eamonn MM. Quigley, Leslie J. Cloud, On behalf of the Other Non-motor Features Working Group of the Parkinson Study Group
Type: Review

Abstract:

Background
Gastrointestinal (GI) dysfunction is a common non-motor feature of Parkinson disease (PD). GI symptoms may start years before the onset of motor symptoms and impair quality of life. Robust clinical trial data is lacking to guide screening, diagnosis and treatment of GI dysfunction in PD.
Objective
To develop consensus statements on screening, diagnosis, and treatment of GI dysfunction in PD.
Methods
The application of a modified Delphi panel allowed for the synthesis of expert opinions into clinical statements. Consensus was predefined as a level of agreement of 100% for each item. Five virtual Delphi rounds were held. Two movement disorders neurologists reviewed the literature on GI dysfunction in PD and developed draft statements based on the literature review. Draft statements were distributed among the panel that included five movement disorder neurologists and two gastroenterologists, both experts in GI dysmotility and its impact on PD symptoms. All members reviewed the statements and references in advance of the virtual meetings. In the virtual meetings, each statement was discussed, edited, and a vote was conducted. If there was not 100% consensus, further discussions and modifications ensued until there was consensus.
Results
Statements were developed for screening, diagnosis, and treatment of common GI symptoms in PD and were organized by anatomic segments: oral cavity and esophagus, stomach, small intestine, and colon and anorectum.
Conclusions
These consensus recommendations offer a practical framework for the diagnosis and treatment of GI dysfunction in PD.
Access this article: https://doi.org/10.1016/j.parkreldis.2024.106982

Title: Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial
Authors: Arnout Bruggeman, Charysse Vandendriessche, Hannelore Hamerlinck, Danny De Looze, David J. Tate, Marnik Vuylsteke, Lindsey De Commer, Lindsay Devolder, Jeroen Raes, Bruno Verhasselt, Debby Laukens, Roosmarijn E. Vandenbroucke, Patrick Santens
Type: Research Article

Summary:

Background
Dysregulation of the gut microbiome has been implicated in Parkinson's disease (PD). This study aimed to evaluate the clinical effects and safety of a single faecal microbiota transplantation (FMT) in patients with early-stage PD.
Methods
The GUT-PARFECT trial, a single-centre randomised, double-blind, placebo-controlled trial was conducted at Ghent University Hospital between December 01, 2020 and December 12, 2022. Participants (aged 50–65 years, Hoehn and Yahr stage 2) were randomly assigned to receive nasojejunal FMT with either healthy donor stool or their own stool. Computer-generated randomisation was done in a 1:1 ratio through permutated-block scheduling. Treatment allocation was concealed for participants and investigators. The primary outcome measure at 12 months was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score obtained during off-medication evaluations. Intention-to-treat analysis was performed using a mixed model for repeated measures analysis. This completed trial is registered on ClinicalTrials.gov (NCT03808389).
Findings
Between December 2020 and December 2021, FMT procedures were conducted on 46 patients with PD: 22 in the healthy donor group and 24 in the placebo group. Clinical evaluations were performed at baseline, 3, 6, and 12 months post-FMT. Full data analysis was possible for 21 participants in the healthy donor group and 22 in the placebo group. After 12 months, the MDS-UPDRS motor score significantly improved by a mean of 5.8 points (95% CI −11.4 to −0.2) in the healthy donor group and by 2.7 points (−8.3 to 2.9) in the placebo group (p = 0.0235). Adverse events were limited to temporary abdominal discomfort.
Interpretation
Our findings suggested a single FMT induced mild, but long-lasting beneficial effects on motor symptoms in patients with early-stage PD. These findings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages.
Access this article: https://doi.org/10.1016/j.eclinm.2024.102563

Title: Electroacupuncture blocked motor dysfunction and gut barrier damage by modulating intestinal NLRP3 inflammasome in MPTP-induced Parkinson’s disease mice
Authors: Lei Guo, Haiming Hu, Nan Jiang, Huabing Yang, Xiongjie Sun, Hui Xia, Jun Ma, Hongtao Liu
Type: Research Article

Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder commonly accompanied by gut dysfunction. EA has shown anti-inflammatory and neuroprotective effects. Here, we aim to explore whether EA can treat Parkinson’s disease by restoring the intestinal barrier and modulating NLRP3 inflammasome. We applied 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish a PD mouse model and EA at the GV16, LR3, and ST36 for 12 consecutive days. The open-field test results indicated that EA alleviated depression and behavioral defects, upregulated the expressions of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF), and blocked the accumulation of α-synuclein (α-syn) in the midbrain. Moreover, EA blocked the damage to intestinal tissues of PD mice, indicative of suppressed NLRP3 inflammasome activation and increased gut barrier integrity. Notably, the antibiotic-treated mouse experiment validated that the gut microbiota was critical in alleviating PD dyskinesia and intestinal inflammation by EA. In conclusion, this study suggested that EA exhibited a protective effect against MPTP-induced PD by alleviating behavioral defects, reversing the block of motor dysfunction, and improving the gut barrier by modulating intestinal NLRP3 inflammasome. Above all, this study could provide novel insights into the pathogenesis and therapy of PD.
Access this article: https://doi.org/10.1016/j.heliyon.2024.e30819

Title: Efficacy of probiotic supplements on Parkinson's disease: A systematic review and meta-analysis
Authors: Xiaxia Jin, Wendi Dong, Kaile Chang, Yongmei Yan, Xiaochun Liu
Type: Review

Abstract:

Objective
This study aimed to evaluate the clinical efficacy and safety of probiotics supplementation in the treatment of Parkinson's disease (PD).
Methods
We searched China National Knowledge Infrastructure (CNKI), Weipu (VIP) database, Wanfang Database, Sinomed (CBM), PubMed, Embase, Cochrane library and Web of Science databases for eligible studies from inception to January 4th, 2024. Randomized controlled trials (RCTS) comparing the effects of probiotic supplements and placebo in patients with PD. Meta-analysis was conducted with the software Review Manager 5.4. The quality assessment was performed according to Cochrane risk of bias tool.
Results
A total of 11 RCTs with 756 PD patients were included in this study. We found that probiotics could increase the number of complete bowel movements (CBMs) per week and improved the scores of Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) (SMD = 0.73, 95 % CI: 0.54 to 0.92, P < 0.00001, I2 = 45 %; SMD = − 0.79, 95 % CI: − 1.19 to − 0.39, P < 0.001, I2 = 55 %, respectively) compared with the placebo group. However, there was no significant difference between the two groups in improving fecal traits and defecation efforts in PD patients (SMD = 0.87, 95 % CI: 0.01 to 1.74, P = 0.05, I2 = 94 %; SMD = 1.24, 95 % CI: − 1.58 to 4.06, P > 0.05, I2 = 98 %, respectively). In terms of PD composite scale scores: after treatment, there was no significant difference in Movement Disorder Society-Unified-Parkinson Disease Rating Scale Ⅲ score (MDS-UPDRSⅢ) between the probiotic group and the placebo group (SMD = − 0.09, 95 % CI: − 0.35 to 0.16, P > 0.05, I2 = 0 %).
Conclusions
In conclusion, based on the overall results of the available RCTs studies, our results suggested the potential value of probiotics in improving constipation symptoms in PD patients. Therefore, probiotics may be one of the adjuvant therapy for PD-related constipation patients. The findings of this study provide more proof supporting the effectiveness of probiotics, encouraging probiotics to be utilized alone or in combination with other therapies in clinical practice for PD patients. However, more well-designed RCTs with large sample sizes are required.
Access this article: https://doi.org/10.1016/j.ctim.2024.103045