Impacts of Bariatric Surgery on the Microbiome and Brain Function

NCT05318781 | Unknown

• 1 other identifier: MP-32-2022-2412
• Study Type: observational
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

Emerging evidence suggests that dietary and metabolic interventions could potentially target prevention and supportive therapies as well as treatments that may slow the clinical deterioration of neurodegenerative disorders. Though certain dietary patterns can impair specific cognitive domains, e.g., declines in reasoning and global cognition, there is still no consensus on the optimal diet to maintain brain health. Studies have also shown an association between the gut microbiome and neurocognition, as the microbiota can affect neuronal function through neurotransmitters and neuroactive microbial metabolites. Furthermore, studies indicate that diet may strongly influence the gut microbiota. However, the mechanisms for these complex relationships are still poorly understood. Bariatric procedures \[i.e., weight loss surgeries\] create a unique environment, in which a fast change in gut microbiota composition and dietary patterns occurs through surgery-induced intestinal and metabolic modifications, leading to changes in gut-brain communication. Interestingly, improvements in neurocognitive domains including memory and executive function have been reported post-bariatric surgery. However, there is large variability in these outcomes, indicating that the benefits are not universal. The goal of the current study is to explore the associations between dietary patterns and gut microbiota with cognition and brain structure, using bariatric surgery as an efficient naturalistic experimental design. This project will also explore potential mediators of diet-microbiome alterations as they relate to improvements in brain function and structure. A total of 120 adult patients (\> 30y yrs.) scheduled to undergo a first bariatric surgery along with 60 age-, sex-, and BMI-matched waitlist control group will be recruited from the bariatric surgery clinic at the CIUSSS du Nord-de-l'Île-de-Montréal. These individuals will undergo assessments 3 months before surgery, as well as 6- and 12-months post-surgery, or an equivalent time for those on the waitlist. This study will also include 60 age-and sex-matched individuals who are not eligible for bariatric surgery as an additional healthy Canadian comparison group (only one assessment time point). Assessments taken during the data collection period will include: self-report information \[e.g., sociodemographic and background information, health and diet behaviours\]; information from medical records \[e.g., medications usage, peri- and post-surgical complications, etc.\]; physiological measures \[i.e., blood, urine and fecal samples collection\]; cognitive assessment \[i.e., neuropsychological tests battery\]; and brain imaging \[i.e., structural MRI\]. Collectively, this study is designed to provide critical information about potential individually targeted diet-based preventative strategies to reduce the development and progression of neurodegenerative disorders. Moreover, this project will explore potential mediators of diet-microbiome alterations as they relate to improvements in brain function and structure, and as such, it will provide essential information on key mechanisms, stimulating further research and the creation of parallel non-dietary therapeutic options.

Conditions

Bariatric Surgery Candidate; Weight Loss

Keywords

Bariatric surgery; Microbiota; Diet; Cognition; Brain structure

Outcome Measures

Primary Outcomes (1)

• Changes in cognition from baseline [3 months pre-surgery] to 12 months post-surgery, measured using sensitive neuropsychological test battery [NTB]

  Global cognition will be assessed using the NTB total score (the primary outcome), a composite NTB score of 14 sub-tests. NTB domain Z scores for executive functioning, processing speed, and memory will also be calculated.

  3 months pre- and 12 months post-surgery [or equivalent time point for waitlist participants]

Secondary Outcomes (2)

• Changes in MRI-derived brain volume from baseline [3 months pre-surgery] to 12 months

  3 months pre- and 12 months post-surgery [or equivalent time point for waitlist participants]

• Changes in MRI-derived white-matter hyperintensities from baseline [3 months pre-surgery] to 12 months post-surgery

  3 months pre- and 12 months post-surgery [or equivalent time point for waitlist participants]

Other Outcomes (20)

• Trajectories of clusters of gut microbiota composition measured with Metagenomic shotgun sequencing from baseline through to 12 months post-surgery

  3 months pre- and 6 and 12 months post-surgery [or equivalent time point for waitlist participants]

• Trajectories of clusters of gut microbiota composition measured with High-throughput sequencing of 16 S rRNA genes from baseline through to 12 months post-surgery

  3 months pre- and 6 and 12 months post-surgery [or equivalent time point for waitlist participants]

• Trajectories of macro-level dietary intake from baseline through to 12 months post-surgery

  3 months pre- and 6 and 12 months post-surgery [or equivalent time point for waitlist participants]

Study Arms (3)

Patients undergoing bariatric surgery

Adult patients (≥ 30y yrs.) scheduled to undergo a first bariatric surgery recruited from the bariatric surgery clinic at the CIUSSS du Nord-de-l'Île-de-Montréal \[N=120\]

Patients on the bariatric surgery waitlist

Age-, sex-, and BMI-matched waitlist control group \[awaiting for bariatric surgery\] recruited from the bariatric surgery clinic at the CIUSSS du Nord-de-l'Île-de-Montréal \[N=60\]

Non-bariatric eligible individuals

Age-and sex-matched individuals who are not eligible for bariatric surgery, as an additional non-bariatric comparison group \[N=60\] \*The 60 age-and sex-matched non-bariatric participants will have data captured just once \[at baseline\] on a limited number of key assessments

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

A total of 120 adult patients (≥ 30y yrs.) scheduled to undergo a first bariatric surgery (i.e., no previous surgery-related disruption to the gut microbiota), along with 60 age-, sex-, and BMI-matched waitlist control group will be recruited from the bariatric surgery clinic at the CIUSSS du Nord-de-l'Île-de-Montréal, which conducts around 1,000 surgeries per year with a waitlist of approximately 1,000 individuals, with an average wait of 3 years. Volunteers for the non-bariatric eligible individuals group \[healthy control group\] will be recruited using advertisements, recruitment materials will include a short description of the study and details of who is eligible to participate.

You may qualify if:

• Age 30 years or older
• Indeviduals planning to be available for two years of follow-up
• Ability ro read and speak French or English

You may not qualify if:

• A previous bariatric surgery
• Using long-term antibiotics
• Using commercially available prebiotic/probiotic in the past month
• A history of significant intestinal disease/disorder that would influence the microbiome (e.g., Crohn's disease)
• A non-bariatric surgery in the 6 months before being recruited
• A diagnosed neurologic disorder or deficits (e.g., dementia, stroke, or seizures)
• A diagnosis of a severe axis 1 psychotic disorder (e.g., schizophrenia) or bipolar disorder
• A current infection or a diagnosed infectious disease
• Pregnacy or breast feeding
• Active cancer
• Advanced kidney disease
• Advanced liver disease
• Past organ transplantation
• Having any contraindications for undergoing MRI \[i.e., having a cardiac pacemaker (or pacemaker), defibrillator (a heart rhythm device), heart valve prosthesis (a prosthesis in the heart), Swan-Ganz catheter (a tube in the pulmonary artery on the chest), metal insulin or chemotherapy pump under the skin, neurostimulator, brain aneurysm clip (a clip in a blood vessel of the brain), metal prosthesis or rods (following surgery), metal cerclage (metal support on a bone), cochlear or ocular implant (an implant in the ear or eye), penile implant, an intraocular metal fragment (metal debris in the eye), an intrauterine device that does not conform with the MRI, any plastic implants (e.g., breasts) or a patch on the skin for the administration of a medication unless it can remove before scan session\]. Additional requirements for MRI includes patients agreement to: 1) have a pregnancy test and remove makeup, 2) the removal of dentures (full or partial), and 3) provide information on all surgery and previous tattoos (tattoos made for many years or those made in some countries, as the ink contains metallic particles).
• For participants included in the non-bariatric eligible comparison group group, individuals with any physician diagnosed major non-communicable chronic disease, defined as cardiovascular disease, chronic obstructive lung disease, cancer, diabetes, or obesity, will be excluded.

Sponsors & Collaborators

• Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal: lead
• Concordia University, Montreal: collaborator
• Centre de Recherche de l'Institut Universitaire de Geriatrie de Montreal: collaborator
• University of Ottawa: collaborator

Study Sites (1)

Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, H4J 1C5, Canada

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Samples retained include serum, urine, plasma, stool for high-throughput sequencing of 16SrRNA and metagenomic shotgun sequencing

MeSH Terms

Conditions

Weight Loss

Condition Hierarchy (Ancestors)

Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Simon Bacon, PhD

  Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: April 8, 2022
• Study Start: August 1, 2022
• Primary Completion: January 1, 2025
• Study Completion: May 1, 2025
• Last Updated: August 3, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)