Multiple Sclerosis, Parkinson Disease, REM Sleep Behavior Disorder
Conditions
Brief summary
The purpose of this study is to ascertain the functional profiles of the immune cells within the gastrointestinal tract and to determine how these cells contribute to autoimmune and neurologic diseases.
Detailed description
Immune cells and microbes within the GI tract likely play an important role for neurologic disease pathogenesis, including MS and Parkinson's disease. Nevertheless, these immune cells have never been studied in detail using modern single cell technologies. Moreover, most of the human microbiome work done in this space to date has utilized fecal samples, but different anatomic niches within the gut may have greater importance for disease. This study will provide seminal information about how the relationships between gut immunity and neurologic/autoimmune diseases and may be paradigm shifting in regards to how the pathogenesis of some neurologic diseases is viewed. This is an observational cohort study. Individuals undergoing colonoscopy (+/- upper endoscopy) as a part of standard of care or who consent to have a colonoscopy (+/- upper endoscopy) will be recruited to provide tissue biopsies obtained from the gastrointestinal mucosa. The rationale for including those who are not yet due to have a screening colonoscopy is that for many neurologic diseases (like MS), the disease onset is in adolescence or early adulthood, and the disease is diagnosed in young adults. These individuals would not yet be due to have screening colonoscopies, and yet changes in immune cells within the intestines may be a critical part of disease pathogenesis. This is what the investigators are exploring with this study. The investigators will need to recruit age matched healthy controls because many features of the immune system change with age; as people get older, the immune system becomes less inflammatory ("immune senescence") and thus it is essential to have age-matched tissues for comparison.
Interventions
PROCEDUREColon Tissue Biopsy
Colonoscopy and colon tissue biopsy.
Sponsors
Yale University
National Institutes of Health (NIH)
Chan Zuckerberg Biohub
The Brain Research Foundation
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18 and up ONE of the following: * Recommended to under a screening colonoscopy (+/- upper endoscopy) as part of standard of care. This includes healthy individuals as well as those with neurologic and/or autoimmune diseases. OR * Willing to undergo research colonoscopy (+/- upper endoscopy) for research
Exclusion criteria
* Currently pregnant. Women of childbearing potential would perform a point of care urine pregnancy test prior to colonoscopy/endoscopy. * Known or suspected, chronic inflammatory gastrointestinal disease (e.g. inflammatory bowel disease) * Known, acute or chronic infections * Systemic antibiotic (PO or IV) use within 3 months of colonoscopy * Systemic corticosteroid use (equivalent of prednisone 10 mg per day or higher for \>5 days) within 2 weeks of colonoscopy * Malignancy, diagnosed or treated within the last 5 years * Probiotic use within 2 weeks of procedure * History of major GI surgery (e.g. colon resection, gastric bypass) * Bleeding disorder, or on anticoagulant medication * Other medical condition that, in the judgement of the investigator, would lead to higher-than-expected risks of biopsy * Allergy to MAC anesthesia or other drugs used pursuant to standard of care for biospecimen collection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterization of immune cells from the gastrointestinal mucosa | Through study completion, an average of 5 years | Gastrointestinal mucosa cells will be characterized using sRNA measured through high-throughput sequencing with quantitative polymerase chain reaction (qPCR) validation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate spatial transcriptomics of intestinal tissue | Through study completion, an average of 5 years | Spatial transcriptomics will be performed on gut mucosal biopsies |
| Characterize the microbiome at different anatomic sites within the gastrointestinal tract | Through study completion, an average of 5 years | 16S and/or shotgun metagenomic sequencing will be utilized to assess the composition of gut microbiome |
Countries
United States
Contacts
CONTACTCynthia Marques
CONTACTDimitri Duvilaire
PRINCIPAL_INVESTIGATORErin Longbrake
Yale University
Outcome results
None listed