Single-center Pathophysiological Study of the Role of Inflammation, Changes in the Intestinal Epithelial Barrier and the Intestinal Microbiota in Parkinson's Disease

Single-center Pathophysiological Study of the Role of Inflammation, Changes in the Intestinal Epithelial Barrier and the Intestinal Microbiota in Parkinson's Disease

Converging evidence from the literature suggests that digestive inflammation may play a role in the development of Parkinson's disease (PD). The investigators showed in the laboratory in a pilot study that PD patients have digestive inflammation and that the level of inflammation was inversely related to the length of the disease course. This digestive inflammation could be at the origin of an increased intestinal permeability in a subpopulation of parkinsonian patients, cause or consequence of modifications of the intestinal microbiota, thus offering a potential portal of entry for a pathogen according to Braak's theory. To opponents of this theory, it could also reflect the spread of inflammation from the Central nervous System to the Enteral Nervous System (ENS), via the brain-gut axis.

Investigators' hypothesis is that digestive inflammation occurs very early in Parkinson's disease and that it is associated with hyperpermeability of the intestinal epithelial barrier and a change in the intestinal microbiota composition. The investigators propose to study the inflammation markers in the ENS of patients with a pre-motor form of PD (idiopathic Rapid Eye Movement (REM) sleep behavior disorder, n = 20), early-stage PD (<5 years, without dopatherapy, n = 20), more advanced PD (> 5 years, n = 20) and control subjects (n = 20), on colonic biopsies taken during a rectosigmoidoscopy or a coloscopy. Intestinal permeability will be measured by ex-vivo techniques (in a Ussing chamber), the composition of the microbiota will be established by sequencing 16s RNA and the lesional load of phosphorylated alpha-synuclein will be evaluated by immunohistochemistry. All of these parameters will be correlated with clinical data on the severity of PD: duration of development, age, total Unified Parkinson's Disease Rating Scale (UPDRS) motor score and axial sub-score, cognitive tests (Montreal Cognitive Assessment, MoCA), existence of a probable idiopathic REM sleep behavior disorder (REM Sleep Behavior Disorder Screening Questionnaire RBDSQ), olfactory tests, complaint of dysautonomia (SCales for Outcomes in Parkinson's disease - autonomic dysfunction, SCOPA-Aut).

The analysis of inflammation markers, the intestinal barrier and the microbiota could be a first step making it possible to formulate physiopathological hypotheses on the development of PD, to propose predictive biomarkers of the disease and its severity and to design early interventions in the hope of modifying the evolutionary course of the pathological process.

Inclusion Criteria:

Parkinson's Disease patients :

• patients with Parkinson's disease according to the criteria of the United Kingdom Parkinson's disease survey brain bank (UKPDSBB)
• aged over 18 years
• who have given their consent to participate in this study

Idiopathic REM sleep behavior disorders patients:

• patients with an Idiopathic REM sleep behavior disorder confirmed by video-polysomnography (International Classification of Sleep Disorders-3 criteria), not explained by a pathology (narcolepsy, brainstem injury, neurodegenerative disease)
• aged over 18 years
• having given their consent to participate in this study

Control:

• patients undergoing coloscopy for family screening for digestive polyps
• aged over 18
• who have given their consent to participate in this study

Exclusion Criteria:

• dementia (MINI MENTAL STATE EXAMINATION score <24)
• history of authenticated colonic disease (inflammatory disease, adenocarcinoma) or functional colopathy in control subjects or having preceded the first signs of Parkinson's Disease or Idiopathic REM sleep behavior disorder for more than 5 years, respectively in Parkinson's Disease and Idiopathic REM sleep behavior disorder patients
• history of prescription of antibiotic treatment, acute gastrointestinal illness or hospitalization for an acute medical pathology or for a surgical procedure in the last month
• anticoagulant treatment or coagulopathy
• pregnant or breastfeeding women, woman not benefiting from effective contraception if of childbearing age
• adults under tutorship, curatorship or under legal protection

For patients with Idiopathic REM sleep behavior disorder:

- presence of Parkinson's Disease according to United Kindom Parkinson's Disease Brain Bank criteria

For control:

• presence of a Parkinson's Disease according to United Kindom Parkinson's Disease Brain Bank criteria
• complaint of nighttime unrest in favor of a probable Idiopathic REM sleep behavior disorder