Constipation In Parkinson's Disease Research Articles

Defecatory disorders are a common cause of chronic constipation in Parkinson disease.

Up to 50% of patients with Parkinson disease have constipation (PD-C), but the prevalence of defecatory disorders caused by rectoanal dyscoordination in PD-C is unknown. We aimed to compare anorectal function of patients with PD-C versus idiopathic chronic constipation (CC). Anorectal pressures, rectal sensation, and rectal balloon expulsion time (BET) were measured with high-resolution anorectal manometry (HR-ARM) in patients with PD-C and control patients with CC, matched for age and sex. We identified 97 patients with PD-C and 173 control patients. Eighty-six patients with PD-C (89%) had early PD, and 39 (40%) had a defecatory disorder, manifest by a prolonged rectal balloon expulsion time (37 patients) or a lower rectoanal pressure difference during evacuation (2 patients). PD-C patients with a prolonged BET had a greater anal resting pressure (p = 0.02), a lower rectal pressure increment (p = 0.005), greater anal pressure (p = 0.047), and a lower rectoanal pressure difference during evacuation (p < 0.001). Rectal sensory thresholds were greater in patients with abnormal BET. In the multivariate model comparing CC and PD-C (AUROC = 0.76), PD-C was associated with a lower anal squeeze increment (odds ratio [OR] for PD-C, 0.93 [95% CI, 0.91-0.95]), longer squeeze duration (OR, 1.05 [95% CI, 1.03-1.08]), lower rectal pressure increment (OR per 10 mm Hg, 0.72 [95% CI, 0.66-0.79]), and negative rectoanal gradient during evacuation (OR per 10 mm Hg, 1.16 [95% CI, 1.08-1.26]). Compared with CC, PD-C was characterized by impaired squeeze pressure, longer squeeze duration, lower increase in rectal pressure, and a more negative rectoanal gradient during evacuation.

Distinct Patterns of Gene Expression Changes in the Colon and Striatum of Young Mice Overexpressing Alpha-Synuclein Support Parkinson's Disease as a Multi-System Process.

Evidence supports a role for the gut-brain axis in Parkinson's disease (PD). Mice overexpressing human wild type α- synuclein (Thy1-haSyn) exhibit slow colonic transit prior to motor deficits, mirroring prodromal constipation in PD. Identifying molecular changes in the gut could provide both biomarkers for early diagnosis and gut-targeted therapies to prevent progression. To identify early molecular changes in the gut-brain axis in Thy1-haSyn mice through gene expression profiling. Gene expression profiling was performed on gut (colon) and brain (striatal) tissue from Thy1-haSyn and wild-type (WT) mice aged 1 and 3 months using 3' RNA sequencing. Analysis included differential expression, gene set enrichment and weighted gene co-expression network analysis (WGCNA). At one month, differential expression (Thy1-haSyn vs. WT) of mitochondrial genes and pathways related to PD was discordant between gut and brain, with negative enrichment in brain (enriched in WT) but positive enrichment in gut. Linear regression of WGCNA modules showed partial independence of gut and brain gene expression changes. Thy1-haSyn-associated WGCNA modules in the gut were enriched for PD risk genes and PD-relevant pathways including inflammation, autophagy, and oxidative stress. Changes in gene expression were modest at 3 months. Overexpression of haSyn acutely disrupts gene expression in the colon. While changes in colon gene expression are highly related to known PD-relevant mechanisms, they are distinct from brain changes, and in some cases, opposite in direction. These findings are in line with the emerging view of PD as a multi-system disease.

Research status and prospect on the mechanisms of acupuncture and moxibustion treatment for constipation of Parkinson's disease.

Constipation may accelerate the progression of Parkinson's disease (PD). The quality of life in PD patients can be significantly improved when constipation is treated, hence the disease progression may be delayed. At present, the mechanism research is still at the initial stage for acupuncture in treatment of PD, focusing on neurohumoral factors, intestinal flora, bacterial fermentation products and intestinal inflammation； and there are the problems such as single intervention, thinking limitation and insufficient cooperation among disciplines. This paper systematically reviews the mechanism research progress of acupuncture for the treatment of constipation in PD so as to provide the references for the subsequent studies.

Constipation in Parkinson's Disease.

Constipation is one of the most common gastrointestinal features of Parkinson's disease (PD), occurring in over 50% of all PD patients during the course of their disease. Furthermore, constipation is now recognized as an important, prodromal symptom and may predate the onset of the classical motor symptoms by decades. Thereafter, the prevalence and severity of constipation in PD tend to parallel the course of both motor and nonmotor phenomena such as cognitive decline and depression. Difficult defecation (obstructed defecation, dyssynergia) is the primary pathophysiology underlying constipation and likely reflects involvement by the PD process of one or more of the many skeletal muscle groups that are involved in effecting defecation. Management of constipation in PD may be complicated by several patient factors including dysphagia, cognitive impairment, depression, and weak sphincter tone. While the armamentarium available to those who treat constipation, in general, has expanded considerably in recent years, the evidence supporting any therapy in the management of this symptom in PD has remained slim.

Parkinson's disease patients combined with constipation tend to have higher serum expression of microRNA 29c, prominent neuropsychiatric disorders, possible RBD conversion, and a substandard quality of life.

The symptom of constipation has been confirmed as an early diagnose criteria for Parkinson's disease (PD). Furthermore, evidences suggest that pathogenesis of PD initiates in gut, rather than brain. If so, identifying biomarkers for constipation in PD might have potentials to assist early diagnosis and initial treatment. We first identified that microRNA 29c (miR-29c) was dysregulated both in PD and constipation patients through bioinformatics analysis. Then, serological analysis of the expression of miR-29c in 67 PD patients with constipation (PD-C), 51 PD patients without constipation (PD-NC), and 50 healthy controls (HC) was carried out by qPCR. Demographic and clinical features were also compared. Patients in PD-C group were further classified into two groups: those with prodromal stage constipation (PD-C-Pro) (n = 36) and those with clinical stage constipation (PD-C-Clinic) (n = 31), to explore their different characteristics. The levels of miR-29c in PD-C group were higher than that in PD-NC group, both higher than HC group. PD-C-Pro group's miR-29c levels were statistically higher compared with PD-C-Clinic group's. What is more, PD-C group had higher scores of MDS-UPDRS-I, NMSS, NMSS3, NMSS4, NMSS6, NMSS9, SCOPA-AUT, HAMD, HAMA, RBDSQ, CSS, and PACQOL compared with PD-NC party. Relative to the PD-C-Clinic, patients in PD-C-Pro group had higher MDS-UPDRS-I, NMSS, NMSS3, HAMD, and HAMA scores, and were more likely to have RBD. Our results indicated that miR-29c seems to be an underlying cause for developing constipation in patients with PD and PD-C identifies a group of patients with more severe non-motor impairment, prominent neuropsychiatric disorders, and possible RBD conversion as well as a substandard quality of life. We further confirmed that there is a close relationship between symptoms representing the same pathological origin, especially constipation and RBD.

The effect of electroacupuncture at ST25 on Parkinson's disease constipation through regulation of autophagy in the enteric nervous system.

The effectiveness and safety of electroacupuncture (EA) for constipation have been confirmed by numerous clinical studies and experiments, and there are also studies on the efficacy of EA for Parkinson's disease (PD) motor symptoms. However, there are few researches on EA for PD constipation. Autophagy is thought to be involved in the mechanistic process of EA in the central nervous system (CNS) intervention in Parkinson's pathology. However, whether it has the same effect on the enteric nervous system (ENS) has not been elucidated. Therefore, we investigated whether EA at Tianshu (ST25) acupoint promotes the clearance of α-Syn and damaged mitochondria aggregated in the ENS in a model of rotenone-induced PD constipation. This study evaluated constipation symptoms by stool characteristics, excretion volume, and water content, and the expression levels of colonic ATG5, LC3II, and Parkin were detected by Western Blot (WB) and Real-Time Quantitative PCR (RT-qPCR). The relationship between the location of α-Syn and Parkin in the colonic ENS was observed by immunofluorescence (IF). The results showed that EA intervention significantly relieved the symptoms of rotenone-induced constipation in PD rats, reversed the rotenone-induced down-regulation of colonic ATG5, LC3II, and Parkin expression, and the positional relationship between colonic α-Syn and Parkin proved to be highly correlated. It is suggested that EA might be helpful in treating PD constipation by modulating Parkin-induced mitochondrial autophagy.

Electroacupuncture for motor dysfunction and constipation in patients with Parkinson's disease: a randomised controlled multi-centre trial

Motor disturbances and non-motor disturbances such as constipation are the main factors affecting the quality of life in patients with Parkinson's disease (PD). We investigated the efficacy and safety of electroacupuncture combined with conventional pharmacological treatment on motor dysfunction and constipation in PD. In this multi-centre randomised controlled trial, we enrolled 166 eligible participants between September 19, 2018 and September 25, 2019 in four hospitals in China. Participants were randomly assigned (1:1) to the electroacupuncture (EA) group and the waitlist control group. Each participant in both groups received the conventional pharmacological treatment, EA group received 3 sessions of electroacupuncture per week for 12 weeks. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline to week 12. The secondary outcomes included the evaluation of functional disability in motor symptoms and constipation, the adherence and adverse events were also recorded. Registered with Chictr.org.cn, ChiCTR1800019517. At week 12, the change in the UPDRS score of the EA group was significantly higher than that of the control group, with a difference of-9.1 points (95% CI,-11.8 to-6.4), and this difference continued into weeks 16 and 24. From baseline to week 12, the 39-item Parkinson Disease Question (PDQ-39) decreased by 10 points (interquartile range, IQR-26.0 to 0.0) in the EA group and 2.5 points (IQR:-11.0 to 4.0) in the control group, the difference was statistically significant. The time and steps for the 20-m walk at week 12, as well as the changes from baseline in the EA group, were comparable with that in the control group. But the EA group had a greater decrease than the control group from baseline in the times for 20-m walks at weeks 16 and 24. From week 4 to week 24, the median values of spontaneous bowel movements (SBMs) per week in the EA group were higher than that in the control group, the differences were all statistically significant. The incidence of EA-related adverse events during treatment was low, and they are mild and transient. The findings of our study suggested that compared with conventional pharmacological treatment, conventional pharmacological treatment combined with electroacupuncture significantly enhances motor function and increased bowel movements in patients with PD, electroacupuncture is a safe and effective treatment for PD. Shanghai "Science and Technology Innovation Action Plan" Clinical Medicine Field Project (18401970700), Shanghai Special Project on Aging and Women's and Children's Health Research (020YJZX0134), Shanghai Clinical Research Centre for Acupuncture and Moxibustion (20MC1920500).

Parkinson's disease constipation effect of electroacupuncture at ST25 through colonic motility and enteric neuropathology.

The enteric nervous system (ENS) plays a central role in developing Parkinson's disease (PD) constipation, and the regulation of the ENS may be a key component in treating PD constipation. Electroacupuncture (EA) can effectively treat constipation symptoms in PD, but research on its specific mechanisms, especially in terms of ENS, is relatively lacking. Therefore, we investigated whether EA at ST25 promotes the restoration of ENS structure and colonic motor function in the rotenone-induced PD constipation rat model. In this study, we evaluated constipation symptoms by stool characteristics, excretion and water volume, and whole gut transit time and observed colonic motility regulation through colonic motion detection and pathological changes in the colonic myenteric nervous plexus by transmission electron microscopy and immunofluorescence staining. EA significantly improved the constipation symptoms and positively adjusted the colonic motility in rotenone-induced PD constipation rats. At the same time, EA reversed the rotenone-induced colonic myenteric nervous plexus injury and regulated the ratio of inhibitory and excitatory neurotransmitters. Our results indicate that EA treatment of PD constipation may be mediated through the adjustment of ENS.

Dysbiosis of the Beneficial Gut Bacteria in Patients with Parkinson's Disease from India.

Recent advancement in understanding neurological disorders has revealed the involvement of dysbiosis of the gut microbiota in the pathophysiology of Parkinson's disease (PD). We sequenced microbial DNA using fecal samples collected from PD cases and healthy controls (HCs) to evaluate the role of gut microbiota. Full-length bacterial 16S rRNA gene sequencing of fecal samples was performed using amplified polymerase chain reaction (PCR) products on the GridION Nanopore sequencer. Sequenced data were analyzed using web-based tools BugSeq and MicrobiomeAnalyst. We found that certain bacterial families like Clostridia UCG 014, Cristensenellaceae, and Oscillospiraceae are higher in abundance, and Lachinospiracea, Coriobacteriaceae and genera associated with short-chain fatty acid production, Faecalibacterium, Fusicatenibacter, Roseburia and Blautia, are lower in abundance among PD cases when compared with the HC. Genus Akkermansia, Dialister, Bacteroides, and Lachnospiraceae NK4A136 group positively correlated with constipation in PD. Observations from this study support the other global research on the PD gut microbiome background and provide fresh insight into the gut microbial composition of PD patients from a south Indian population. We report a higher abundance of Clostridia UCG 014 group, previously not linked to PD.

Correction: Oral ENT-01 Targets Enteric Neurons to Treat Constipation in Parkinson Disease

Correction: Oral ENT-01 Targets Enteric Neurons to Treat Constipation in Parkinson Disease

Constipation Management in Parkinson Disease.

BACKGROUND: Constipation is the most frequently reported nonmotor gastrointestinal symptom of Parkinson disease and can precede motor symptoms by up to 20 years. The causes of constipation can be multifactorial, but the implications can lead to life-threatening complications. Early recognition of constipation can lead to better health outcomes and quality of life. MANAGEMENT CONSIDERATIONS: The combination of nonpharmacological management through screening tools, nursing assessment, and patient education as well as pharmacological management is considered best practice. IMPLICATIONS FOR PRACTICE: Nurses who are knowledgeable on the current treatment options for constipation in Parkinson disease will be better equipped as active multidisciplinary team players to provide optimal care to their patients and achieve the best health outcomes.

The Gastrointestinal Dysfunction Scale for Parkinson's Disease.

Gastrointestinal dysfunction is an important feature of Parkinson's disease (PD), and there is increasing evidence that it may play a key role in the disease process. However, its assessment is limited by different tools and underlying differences in diagnostic criteria for gastrointestinal dysfunction. To date, there is no psychometric instrument for quantitative evaluation of gastrointestinal symptoms specifically designed for use in PD. The objective of this study was to develop a self-report questionnaire-based instrument, the Gastrointestinal Dysfunction Scale for Parkinson's Disease, and to evaluate its psychometric properties. We performed a literature review and conducted 3 focus groups to develop the Gastrointestinal Dysfunction Scale for Parkinson's Disease. Three hundred and sixteen patients with PD and 55 controls completed the Gastrointestinal Dysfunction Scale for Parkinson's Disease, the Non-Motor Symptom Scale, the Hospital Anxiety and Depression Scale, and a stool diary adapted from the Bristol Stool Chart. The Gastrointestinal Dysfunction Scale for Parkinson's Disease demonstrated good internal consistency (Cronbach's α=0.82) and test-retest stability (0.79 < ICCs > 0.94). Correlation analyses supported good convergent and divergent validity. Receiver operating characteristic analysis demonstrated that a cutoff score of ≥9 on the Gastrointestinal Dysfunction Scale for Parkinson's Disease Constipation subscale discriminates between PD patients with and without constipation. The Gastrointestinal Dysfunction Scale for Parkinson's Disease is a novel disease-specific self-report tool to quantitatively assess the presence and severity of gastrointestinal dysfunction features in patients with PD, with strong reliability and validity. Further longitudinal studies are needed to demonstrate its utility in tracking gastrointestinal dysfunction in PD clinical cohorts. © 2021 International Parkinson and Movement Disorder Society.

Probiotics for Parkinson's disease: Current evidence and future directions.

The gut–brain axis is a hot topic in Parkinson's disease (PD). It has been postulated that gut pathogens and dysbiosis can contribute to peripheral inflammatory states or trigger downstream metabolic effects that exacerbate the neurodegenerative process in PD. Several preclinical and clinical studies have demonstrated disrupted intestinal permeability, intestinal inflammation, altered gut microbiome, and reduced fecal short‐chain fatty acids in PD. In this regard, microbial‐directed therapies such as probiotics are emerging as potential therapeutic options. Probiotic supplementation is postulated to confer a variety of health benefits due to the diverse functions of these live microorganisms, including inhibition of pathogen colonization, modulation/“normalization” of the microbiome and/or its function, immunomodulatory effects (e.g. reducing inflammation), and improved host epithelial barrier function. Interestingly, several PD animal model studies have demonstrated the potential neuroprotective effects of probiotics in reducing dopaminergic neuronal degeneration. Notably, two randomized placebo‐controlled trials have provided class I evidence for probiotics as a treatment for constipation in PD. However, the effects of probiotics on other PD aspects, such as motor disability and cognitive function, and its long‐term efficacy (including effects on PD drug absorption in the gut) have not been investigated adequately. Further targeted animal and human studies are also warranted to understand the mechanisms of actions of probiotics in PD and to tailor probiotic therapy based on individual host profiles to improve patient outcomes in this disabling disorder.

S0500 Intestinal Methanogen Overgrowth (IMO) in Parkinson's Disease: High Prevalence and Correlation With Constipation

INTRODUCTION: Recent ACG guidelines have defined intestinal methanogenic overgrowth (IMO) and described its clinical significance. The prevalences of small intestinal bacterial overgrowth (SIBO) and IMO in Parkinson's disease (PD) are unclear. SIBO in PD is linked to worse motor symptoms. Treatment of SIBO can improve motor function in PD. Our aim is to quantify the prevalence of SIBO and IMO in Parkinson's disease (PD) subjects with constipation compared to patients with unexplained GI symptoms undergoing glucose breath testing (GBT). METHODS: After an overnight fast and day of low-CHO diet, subjects brushed their teeth and rinsed their mouth with antiseptic mouthwash 2h before test. During GBT, 75 g of glucose dissolved in 250 mL water was administered. Breath samples were obtained at baseline and 15 min intervals for 2 h. Samples are collected in a bag (QuinTron Instrument Company, Inc.) and alveolar gas was analyzed for both H2 and CH4 levels by chromatography (QuinTron Micro Analyzer, QuinTron, Inc.). SIBO was defined as H2 rise of ≥20 ppm from baseline and/or CH4 rise of ≥10 ppm. IMO was defined as any measured CH4 ≥ 10 ppm. Daily bowel movements were assessed by prospective stool diary. Constipation was defined by <3 complete spontaneous bowel movements (CSBMs)/week. RESULTS: Nineteen patients with PD (68.2 ± 7.0 years, F/M = 6/13) underwent breath testing and compared to 158 subjects with unexplained GI symptoms (47.4 ± 15.3 years, F/M = 119/39). 31.6% (6/19) of PD subjects had SIBO versus 23.4% (37/158) of subjects with unexplained GI symptoms (P = 0.95), shown in Table 1. 52.6% (10/19) of PD subjects had IMO compared to 14.6% (23/158) subjects with unexplained GI symptoms (P < 0.001). 36.8% (7/19) had < 3 CSBMs per week. There was significant correlation between constipation and IMO, but not SIBO, Table 2. Higher maximum methane levels during GBT also significantly correlated with the presence of constipation. CONCLUSION: Rates of SIBO are similar between PD subjects with constipation and symptomatic patients undergoing GBT. More than half and significantly more PD subjects with constipation than symptomatic patients undergoing GBT have IMO. IMO and higher methane levels correlate with constipation in PD quantified by a stool diary. Methanogens may play a critical role in non-motor symptoms of PD patients such as constipation. ACKNOWLEDGEMENT: Parkinson's Foundation Translational Research Award.Table 1.: SIBO and IMO prevalence in subjects with PD vs unexplained GI symptomsTable 2.: Correlation between IMO, maximum methane level, and SIBO with constipation

Changes in Gastrointestinal Microbiome Composition in PD: A Pivotal Role of Covariates.

Altered gut microbiota may trigger or accelerate alpha-synuclein aggregation in the enteric nervous system in Parkinson's disease (PD). While several previous studies observed gut microbiota alterations in PD, findings like diversity indices, and altered bacterial taxa itself show a considerable heterogeneity across studies. We recruited 179 participants, of whom 101 fulfilled stringent inclusion criteria. Subsequently, the composition of the gut microbiota in 71 PD patients and 30 healthy controls was analyzed, sequencing V3–V4 regions of the bacterial 16S ribosomal RNA gene in fecal samples. Our goal was (1) to evaluate whether gut microbiota are altered in a southern German PD cohort, (2) to delineate the influence of disease duration, stage, and motor impairment, and (3) to investigate the influence of PD associated covariates like constipation and coffee consumption. Aiming to control for a large variety of covariates, strict inclusion criteria were applied. Finally, propensity score matching was performed to correct for, and to delineate the effect of remaining covariates (non-motor symptom (NMS) burden, constipation, and coffee consumption) on microbiota composition. Prior to matching altered abundances of distinct bacterial classes, orders, families, and genera were observed. Both, disease duration, and stage influenced microbiome composition. Interestingly, levodopa equivalent dose influenced the correlation of taxa with disease duration, while motor impairment did not. Applying different statistical tests, and after propensity score matching to control for NMS burden, constipation and coffee consumption, Faecalibacterium and Ruminococcus were most consistently reduced in PD compared to controls. Taken together, similar to previous studies, alterations of several taxa were observed in PD. Yet, further controlling for PD associated covariates such as constipation and coffee consumption revealed a pivotal role of these covariates. Our data highlight the impact of these PD associated covariates on microbiota composition in PD. This suggests that altered microbiota may mediate the protective effect of i.e., coffee consumption and the negative effect of constipation in PD.

A randomized double-blind placebo-controlled multicenter trial of Bushen Yisui and Ziyin Jiangzhuo formula for constipation in Parkinson disease.

Introduction:Constipation is a common nonmotor symptom of Parkinson disease (PD). Constipation can also impact patient's quality of life. Chinese herbal medicines have been used for the treatment of constipation in PD. This trial will evaluate the efficacy and safety of a Chinese herbal formula Bushen Yisui and Ziyin Jiangzhuo (BYZJ) for the treatment of constipation in PD.Methods and analysis:This randomized, double-blind, placebo-controlled, multicenter clinical trial will involve 4 hospitals in Beijing, China. The study will aim to recruit 90 PD patients with constipation between 30 and 80 years-of age with a score of 1 – 4 on the Hoehn and Yahr scale. Once recruited, Patients will be randomized into a BYZJ group or a placebo group in a 2:1 ratio. The trial will include a 1-week run-in period, a 4-week double-blind treatment period, a 4-week and a 12-week follow-up period. All patients will be educated about PD-related constipation during the run-in period. BYZJ granules and simulated granules will be administered twice daily for 4 weeks to the BYZJ group and the placebo group respectively. Assessments will be performed during run-in period, before the start of treatment (baseline, week 0), and at 4, 8, and 16 weeks. The primary outcome will be measured with the Constipation Severity Instrument, and secondary outcomes will be evaluated with the Patient Assessment of Constipation Quality of Life questionnaire, Bristol Stool Form Scale, Movement Disorders–Unified Parkinson Disease Rating Scale, Nonmotor Symptoms Scale, PD Sleep Scale, Parkinson Fatigue Scale-16. Laxative use (dose and frequency) will also be recorded. Intention-to-treat and per-protocol set analyses will be used to compare symptom improvement between the 2 groups. Any adverse events will be recorded.Discussion:If found effective and safe, BYZJ formula will be one of Chinese herb to treat constipation and even other nonmotor or motor symptoms in PD patients. The results will sustain the broader use of BYZJ formula in PD.

A Study Protocol to Determine the Effect of a Mediterranean Diet Intervention on Improving Gastrointestinal Function in Parkinson’s Disease

Abstract Objectives Constipation is a common and debilitating nonmotor symptom of Parkinson's disease (PD) that is poorly understood and has limited treatment options. A preliminary pilot study conducted at our center suggests that a Mediterranean diet, which emphasizes foods rich in fermentable fibers and antioxidants, can reduce symptoms of constipation in patients with PD, but may also result in unintended reductions in body weight. This may potentially attenuate the benefit of this dietary intervention. The primary outcome of this project is to test the efficacy of a Mediterranean diet intervention on improving the clinical symptoms of constipation in PD. Secondary outcomes will determine the effect of this intervention on body composition, fecal microbial communities and markers of intestinal inflammation and permeability. Methods This is a 10-week, randomized, controlled, parallel study. Participants with PD (diagnosed by a movement disorder neurologist) who have symptoms of constipation and do not follow a Mediterranean diet will be recruited (n = 42). During the 2-week run-in period, participants will undergo neurological, nutritional, and body composition assessments. Urine and stool samples to assess intestinal permeability (urine sugar probe test), inflammation and microbial communities will be collected. Participants will then be randomized to follow the Mediterranean diet or to maintain their habitual diet for 8 weeks. A study dietitian will provide in-person dietary instruction and weekly follow-up via telephone to both groups to support diet adherence and monitor changes in weight and adverse events. Throughout the study, questionnaires will assess dietary intake and gastrointestinal function including laxative usage. Measurements completed at baseline will be repeated at 4 and 8 weeks of the intervention. Results N/A Conclusions We hypothesize that a Mediterranean diet intervention administered by a registered dietitian/nutritionist will result in dietary changes that improve constipation symptoms, reduce intestinal permeability and inflammation, and favor beneficial microbial communities without producing unintended effects on body mass. Funding Sources University of Florida Moonshot Initiative.

Faecal Transplantation, Pro- and Prebiotics in Parkinson's Disease; Hope or Hype?

Faecal microbiome transplantation (FMT) is an attractive technique, because the administration is relatively simple and in general has a mild adverse effect pattern. Moreover, FMT consists of a broad mixture, which could be beneficial, because at this moment it is not known what type of changes in the microbiome are needed. However, except from a few cases no clinical data in Parkinson’s disease (PD) is available yet. There is some indication that FMT might be beneficial in severe constipated PD patients, but the clinical data to support this are very scarce. So, actually there are no good data in the public domain to support FMT at this moment in PD patients. FMT at this moment is a black box with too many unanswered questions, also with respect to safety concerns. Only the administration of species of Lactobacillus and Bifidobacterium over a time period of four to twelve weeks has repeatedly proven to be effective in treating constipation in PD. Also, no solid clinical data are available about the possible effects of probiotic treatment on motor symptoms or progression of PD. Therefore, also probiotic treatments in PD should wait until better clinical data become available, in order to select the right target populations and to have good estimates of the clinical effects to be expected.

Colonic transit, high-resolution anorectal manometry and MRI defecography study of constipation in Parkinson's disease

IntroductionDespite clinical relevance and potential role on the disease pathogenesis, underlying mechanisms of constipation in Parkinson's disease (PD) remain poorly understood. A systematic assessment using complementary physiological investigations was performed to elucidate constipation pathophysiology in order to improve its symptomatic management. MethodsPD patients with constipation were evaluated with clinical questionnaires, colonic transit, high-resolution anorectal manometry and MRI defecography. Results were compared and correlated with clinical features. ResultsA total of 42 patients (69% male; age 68 ± 8 years; disease duration 10.5 ± 6.1 years) were included, of whom 33 (78.6%) had objective constipation defined by < 3 bowel movements per week or straining. Severity of constipation measured by self-administered questionnaires correlated with disease severity, burden of motor and non-motor symptoms but not with age, disease duration or Parkinson's medications. Colonic transit and anorectal function (high-resolution anorectal manometry and/or MRI defecography) was assessed in 15 patients. A combination of both delayed colonic transit and anorectal dysfunction was the pattern most commonly found (60% of patients) and overall anorectal dysfunction was more prevalent than isolated slow transit constipation. Physiological findings were heterogeneous including reduced colonic motility, rectal hyposensitivity, defecatory dyssynergia and poor motor rectal function. ConclusionSubjective constipation in PD is poorly correlated with commonly used definition, assessment questionnaires and physiological results. Multiple complex overlapping pathophysiological mechanisms are responsible including slow transit and anorectal dysfunction. Complementary investigations to assess colonic transit and anorectal function are required in those with refractory symptoms for a systematic assessment and appropriate symptomatic management.

Severe Constipation in Parkinson's Disease and in Parkinsonisms: Prevalence and Affecting Factors.

Background: constipation is one of the most common and disabling non-motor symptoms of Parkinson Disease (PD) and Parkinsonisms (PS). Few studies evaluate the difference of prevalence between PD and PS and the cause leading to a severe constipation in this diseases.Objective: Aim of our study is to evaluate the prevalence of constipation in a population of patients with PD and PS and to evaluate which factors influence the development of severe constipation.Methods: Two hundred and fifty outpatients with PD and 39 with PS were enrolled. Sixty five age-matched healthy subjects served as control. Constipation was assessed using the “Constipation Scoring System” (CSS). All patients underwent a global clinical, functional and neuropsychological assessment including: Unified Parkinson's disease Rating Scale (UPDRS), 6-min Walk Test (6MWT), and Mini-Mental State Examination (MMSE).Results: Data confirm the high prevalence of constipation among patients with PD and PS. Severe constipation affects much more patients with PS. A significant association between total CSS and age, H and Y stage, 6MWT, MMSE, total UPDRS, and UPDRS III was found in PD. In PS patients total CSS was associated with age, 6MWT, total UPDRS, and UPDRS III. Multivariable regression analysis showed that the only variables significantly and independently associated with total CSS in PD patients were age and total UPDRS, both with direct relationship.Conclusions: The reduction of motor performance seems to be the primary cause for developing severe constipation in PD and PS patients. These data suggest that maintain a good quality of gait and endurance may be helpful to reduce the risk of constipation.