Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation

AbstractParkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

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Evaluation of Fecal Microbiota Transplantation in Parkinson's Disease Patients With Constipation

10.21203/rs.3.rs-211163/v1 ◽

2021 ◽

Author(s):

Xiao-yi Kuai ◽

Xiao-han Yao ◽

Li-Juan Xu ◽

Yu-qing Zhou ◽

Li-ping Zhang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Neurodegenerative Disorder ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Motor Symptoms ◽

Gastrointestinal Dysfunction ◽

Before And After ◽

Non Motor Symptoms

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

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New Avenues for Parkinson’s Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota

Biomolecules ◽

10.3390/biom11030433 ◽

2021 ◽

Vol 11 (3) ◽

pp. 433

Author(s):

Marina Lorente-Picón ◽

Ariadna Laguna

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Neurodegenerative Disorder ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Motor Symptoms ◽

Dietary Interventions ◽

Microbiome Research ◽

Disease Modifying

Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder that currently affects 1% of the population over the age of 60 years, and for which no disease-modifying treatments exist. Neurodegeneration and neuropathology in different brain areas are manifested as both motor and non-motor symptoms in patients. Recent interest in the gut–brain axis has led to increasing research into the gut microbiota changes in PD patients and their impact on disease pathophysiology. As evidence is piling up on the effects of gut microbiota in disease development and progression, another front of action has opened up in relation to the potential usage of microbiota-based therapeutic strategies in treating gastrointestinal alterations and possibly also motor symptoms in PD. This review provides status on the different strategies that are in the front line (i.e., antibiotics; probiotics; prebiotics; synbiotics; dietary interventions; fecal microbiota transplantation, live biotherapeutic products), and discusses the opportunities and challenges the field of microbiome research in PD is facing.

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The role of gut dysbiosis in Parkinson's disease: mechanistic insights andtherapeutic options

Brain ◽

10.1093/brain/awab156 ◽

2021 ◽

Author(s):

Qing Wang ◽

Yuqi Luo ◽

K Ray Chaudhuri ◽

Richard Reynolds ◽

Eng-King Tan ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Nervous System ◽

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Gastrointestinal Symptoms ◽

Fecal Microbiota ◽

Motor Symptoms ◽

Treatment Paradigm ◽

New Treatment

Abstract Parkinson's disease is a common neurodegenerative disease in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alteration in gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the central nervous system, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries and alterations of the gut microbiota in Parkinson's disease, and highlight current mechanistic insights on the microbiota-gut-brain axis in disease pathophysiology. We discuss the interactions between production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we also draw attention to diet modification, use of probiotics and prebiotics and fecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.

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The Add-On Effect of Lactobacillus plantarum PS128 in Patients With Parkinson's Disease: A Pilot Study

Frontiers in Nutrition ◽

10.3389/fnut.2021.650053 ◽

2021 ◽

Vol 8 ◽

Author(s):

Chin-Song Lu ◽

Hsiu-Chen Chang ◽

Yi-Hsin Weng ◽

Chiung-Chu Chen ◽

Yi-Shan Kuo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Lactobacillus Plantarum ◽

Outcome Measures ◽

Rating Scale ◽

Controlled Trial ◽

Secondary Outcome ◽

Motor Deficits ◽

Motor Symptoms ◽

Non Motor Symptoms

Background:Lactobacillus plantarum PS128 (PS128) is a specific probiotic, known as a psychobiotic, which has been demonstrated to alleviate motor deficits and inhibit neurodegenerative processes in Parkinson's disease (PD)-model mice. We hypothesize that it may also be beneficial to patients with PD based on the possible mechanism via the microbiome-gut-brain axis.Methods: This is an open-label, single-arm, baseline-controlled trial. The eligible participants were scheduled to take 60 billion colony-forming units of PS128 once per night for 12 weeks. Clinical assessments were conducted using the Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr scale, and change in patient “ON-OFF” diary recording as primary outcome measures. The non-motor symptoms questionnaire, Beck depression inventory-II, patient assessment of constipation symptom, 39-item Parkinson's Disease Questionnaire (PDQ-39), and Patient Global Impression of Change (PGI-C) were assessed as secondary outcome measures.Results: Twenty-five eligible patients (32% women) completed the study. The mean age was 61.84 ± 5.74 years (range, 52–72), mean disease duration was 10.12 ± 2.3 years (range, 5–14), and levodopa equivalent daily dosage was 1063.4 ± 209.5 mg/daily (range, 675–1,560). All patients remained on the same dosage of anti-parkinsonian and other drugs throughout the study. After 12 weeks of PS128 supplementation, the UPDRS motor scores improved significantly in both the OFF and ON states (p = 0.004 and p = 0.007, respectively). In addition, PS128 intervention significantly improved the duration of the ON period and OFF period as well as PDQ-39 values. However, no obvious effect of PS128 on non-motor symptoms of patients with PD was observed. Notably, the PGI-C scores improved in 17 patients (68%). PS128 intervention was also found to significantly reduce plasma myeloperoxidase and urine creatinine levels.Conclusion: The present study demonstrated that PS128 supplementation for 12 weeks with constant anti-parkinsonian medication improved the UPDRS motor score and quality of life of PD patients. We suggest that PS128 could serve as a therapeutic adjuvant for the treatment of PD. In the future, placebo-controlled studies are needed to further support the efficacy of PS128 supplementation.Clinical Trial Registration:https://clinicaltrials.gov/, identifier: NCT04389762.

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Association between White Matter Lesions and Non-Motor Symptoms in Parkinson Disease

Neurodegenerative Diseases ◽

10.1159/000489311 ◽

2018 ◽

Vol 18 (2-3) ◽

pp. 127-132 ◽

Cited By ~ 3

Author(s):

Jeong-Yoon Lee ◽

Ji Sun Kim ◽

Wooyoung Jang ◽

Jinse Park ◽

Eungseok Oh ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

White Matter ◽

Parkinson Disease ◽

Cognitive Dysfunction ◽

Rating Scale ◽

White Matter Lesions ◽

Motor Dysfunction ◽

Motor Symptoms ◽

Non Motor Symptoms

Background: There are only few studies exploring the relationship between white matter lesions (WMLs) and non-motor symptoms in Parkinson disease (PD). This study aimed to investigate the association between WMLs and the severity of non-motor symptoms in PD. Methods: The severity of motor dysfunction, cognitive impairment, and non-motor symptoms was assessed by various scales in 105 PD patients. We used a visual semiquantitative rating scale and divided the subjects into four groups: no, mild, moderate, and severe WMLs. We compared the means of all scores between the four groups and analyzed the association between the severity of WMLs and the specific domain of non-motor symptoms. Results: The non-motor symptoms as assessed by the Non-Motor Symptoms Scale, Parkinson’s Disease Questionnaire (PDQ-39), Parkinson’s Disease Sleep Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Neuropsychiatric Inventory (NPI), and Parkinson Fatigue Scale (PFS) were significantly worse in the patients with moderate and severe WMLs than in those without WMLs. Compared with the no WML group, the scores for motor dysfunction were significantly higher in the mild, moderate, and severe WML groups. The scores for cognitive dysfunction were significantly higher in the patients with severe WMLs than in those without WMLs. The severity of WMLs showed linear associations with PFS, BDI, BAI, NPI, and PDQ-39 scores. The severity of WMLs also correlated linearly with scores for motor and cognitive dysfunction. Conclusions: Among the non-motor symptoms, fatigue, depression, anxiety, and quality of life were significantly affected by WMLs in PD. Confirmation of the possible role of WMLs in non-motor symptoms associated with PD in a prospective manner may be crucial not only for understanding non-motor symptoms but also for the development of treatment strategies.

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Swallowing dysfunctions in Parkinson’s disease patients: a novel challenge for the internist

Italian Journal of Medicine ◽

10.4081/itjm.2019.1117 ◽

2019 ◽

Vol 13 (2) ◽

pp. 91-94 ◽

Cited By ~ 1

Author(s):

Elena Barbagelata ◽

Antonello Nicolini ◽

Paola Tognetti

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Practice ◽

Aspiration Pneumonia ◽

Neurodegenerative Disorder ◽

Movement Pattern ◽

Morbidity And Mortality ◽

Motor Symptoms ◽

Common Causes ◽

Non Motor Symptoms

Parkinson’s disease (PD) is a chronic neurodegenerative disorder with a typical movement pattern, as well as different, less studied non-motor symptoms such as dysphagia. Disease-related disorders in efficacy or safety in the process of swallowing usually lead to malnutrition, dehydration or pneumonia. Dysphagia and subsequent aspiration pneumonia are common causes of morbidity and mortality in those with PD. The aim of this review is to identify and evaluate the existing literature on swallowing disorders in PD and providing recommendations for clinical practice routine.

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Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson’s disease: the PPMI cohort

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2017-316213 ◽

2017 ◽

Vol 89 (1) ◽

pp. 78-88 ◽

Cited By ~ 27

Author(s):

Tanya Simuni ◽

Chelsea Caspell-Garcia ◽

Christopher S Coffey ◽

Daniel Weintraub ◽

Brit Mollenhauer ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

De Novo ◽

Controlled Study ◽

Motor Symptoms ◽

Biological Variables ◽

Significant Difference ◽

Non Motor Symptoms ◽

Updrs Part

ObjectiveTo examine the baseline prevalence and longitudinal evolution in non-motor symptoms (NMS) in a prospective cohort of, at baseline, patients with de novo Parkinson’s disease (PD) compared with healthy controls (HC).MethodsParkinson’s Progression Markers Initiative (PPMI) is a longitudinal, ongoing, controlled study of de novo PD participants and HC. NMS were rated using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part I score and other validated NMS scales at baseline and after 2 years. Biological variables included cerebrospinal fluid (CSF) markers and dopamine transporter imaging.Results423 PD subjects and 196 HC were enrolled and followed for 2 years. MDS-UPDRS Part I total mean (SD) scores increased from baseline 5.6 (4.1) to 7.7 (5.0) at year 2 in PD subjects (p<0.001) versus from 2.9 (3.0) to 3.2 (3.0) in HC (p=0.38), with a significant difference between the groups (p<0.001). In the multivariate analysis, higher baseline NMS score was associated with female sex (p=0.008), higher baseline MDS-UPDRS Part II scores (p<0.001) and more severe motor phenotype (p=0.007). Longitudinal increase in NMS severity was associated with the older age (0.008) and lower CSF Aβ1–42 (0.005) at baseline. There was no association with the dose or class of dopaminergic therapy.ConclusionsThis study of NMS in early PD identified clinical and biological variables associated with both baseline burden and predictors of progression. The association of a greater longitudinal increase in NMS with lower baseline Aβ1–42 level is an important finding that will have to be replicated in other cohorts.Trial registrationClinicalTrials.gov identifier: NCT01141023.

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A clinical-anatomical signature of Parkinson’s Disease identified with partial least squares and magnetic resonance imaging

10.1101/168989 ◽

2017 ◽

Cited By ~ 3

Author(s):

Yashar Zeighami ◽

Seyed-Mohammad Fereshtehnejad ◽

Mahsa Dadar ◽

D. Louis Collins ◽

Ronald B. Postuma ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Least Squares ◽

Partial Least Squares ◽

Large Scale ◽

De Novo ◽

Neurodegenerative Disorder ◽

Clinical Manifestations ◽

Motor Symptoms ◽

Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by a wide array of motor and non-motor symptoms. It remains unclear whether neurodegeneration in discrete loci gives rise to discrete symptoms, or whether network-wide atrophy gives rise to the unique behavioural and clinical profile associated with PD. Here we apply a data-driven strategy to isolate large-scale, multivariate associations between distributed atrophy patterns and clinical phenotypes in PD. In a sample of N = 229 de novo PD patients, we estimate disease-related atrophy using deformation based morphometry (DBM) of T1 weighted MR images. Using partial least squares (PLS), we identify a network of subcortical and cortical regions whose collective atrophy is associated with a clinical phenotype encompassing motor and non-motor features. Despite the relatively early stage of the disease in the sample, the atrophy pattern encompassed lower brainstem, substantia nigra, basal ganglia and cortical areas, consistent with the Braak hypothesis. In addition, individual variation in this putative atrophy network predicted longitudinal clinical progression in both motor and non-motor symptoms. Altogether, these results demonstrate a pleiotropic mapping between neurodegeneration and the clinical manifestations of PD, and that this mapping can be detected even in de novo patients.

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Long-term effectiveness of levodopa-carbidopa intestinal gel on motor and non-motor symptoms in advanced Parkinson’s disease: results of the Italian GLORIA patient population

Neurological Sciences ◽

10.1007/s10072-020-04401-w ◽

2020 ◽

Vol 41 (10) ◽

pp. 2929-2937 ◽

Cited By ~ 1

Author(s):

Angelo Antonini ◽

Pietro Marano ◽

Graziano Gusmaroli ◽

Nicola Modugno ◽

Claudio Pacchetti ◽

...

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Motor Fluctuations ◽

Motor Symptoms ◽

Italian Population ◽

Advanced Parkinson’S Disease ◽

Non Motor Symptoms

Abstract Introduction The GLORIA registry included 375 advanced Parkinson’s disease (PD) patients and evaluated the efficacy and safety of a 24-month levodopa-carbidopa intestinal gel (LCIG) treatment in routine medical care. This analysis focuses on the Italian population, 60 patients treated with LCIG in 7 specialised PD care centres. Methods Hours of “Off” and “On” time were assessed with a modified version of the Unified Parkinson’s Disease Rating Scale (UPDRS) part IV items 39 and 32. Motor fluctuations, dyskinesia, non-motor symptoms, quality of life and safety were evaluated. Results Overall, 42 (70%) out of 60 patients completed the registry. LCIG treatment reduced “Off” time (− 3.3 ± 2.7 h at month 24 (M24), P < 0.0001), increased “On” time with dyskinesia (− 2.6 ± 5.2 h at M12, P = 0.0160), and improved UPDRS II and UPDRS III total scores at M24 (− 4.5 ± 10.6, P = 0.0333 and − 4.9 ± 11.7, P = 0.0229, respectively), Non-Motor Symptom Scale (NMSS) total score (− 21.8 ± 28.5, P < 0.0001) and Parkinson’s Disease Questionnaire-8 item (PDQ-8) total score (− 12.5 ± 23.9, P = 0.0173) versus previous oral therapy. Adverse drug reactions (ADR) possibly or probably related to treatment were reported in 16 (28.6%) patients. Decreased weight (7.1%), polyneuropathy (7.1%) and abdominal pain (5.4%) were the most frequent ADRs while device malfunction (5.4%) and medical device change (5.4%) were the most reported device complaints. Conclusions LCIG improved motor fluctuations, non-motor symptoms and quality of life over 24 months while tolerability was consistent with the established safety profile.

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Levodopa–carbidopa intrajejunal infusion in Parkinson’s disease: untangling the role of age

Journal of Neurology ◽

10.1007/s00415-020-10356-x ◽

2020 ◽

Author(s):

Francesca Morgante ◽

Valentina Oppo ◽

Margherita Fabbri ◽

Enrica Olivola ◽

Chiara Sorbera ◽

...

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Control Group ◽

Motor Symptoms ◽

Study Visit ◽

Non Motor Symptoms

Abstract Objectives Levodopa–Carbidopa Intrajejunal gel (LCIG) infusion is an effective intervention for people with advanced Parkinson’s disease (PD). Although age may not be a limiting factor for LCIG implant, no data are available on late elderly PD (LE-PD) subjects. In this cross-sectional, we aimed to demonstrate if older age may impact on quality of life (QoL), motor and non-motor symptoms severity, and profile of side effects in PD treated with LCIG. Methods Out of 512 PD subjects treated with LCIG at 9 Italian PD centers, we selected 25 LE-PD defined as age ≥ 80 years at last follow-up who were available to attend the study visit. Twenty-five PD patients (Control-PD, defined as age < 75 years at last follow-up) matched to LE-PD by disease and LCIG duration served as control group. The following motor and non-motor variables were ascertained: quality of life (PDQ-8), time spent in ON, wearing-off Questionnaire, Unified PD Rating Scale, freezing of gait questionnaire, Parkinson’s disease sleep scale-2, Non Motor Symptoms Scale (NMSS), and MOCA. Results No statistically significant differences were found between LE-PD and Control-PD on PDQ-8 and several motor and non-motor variables. LE-PD had less frequent and milder impulsive–compulsive behaviors and milder dyskinesia. At multivariable regression, worse quality of life was associated with UPDRS-III and NMSS scores but not to age at study visit and age at LICG implant. Rate of adverse effects was similar in both groups. Drop-out rate calculated in the whole PD cohort was comparable between the two groups. Conclusion Our data provide evidence that valuable LCIG infusion might be achieved in late elderly PD.

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