Gut Microbiome and Depression

December 9, 2024 updated by: Washington University School of Medicine

Role of the Gut Microbiome as Determinant of Depression in Multiple Sclerosis Subjects

The purpose of this project is to determine if specific gut microbiome or gut-derived metabolites are associated with depression in patients with Multiple Sclerosis (pwMS). Mechanistically, the investigators further hypothesize that depression in pwMS is related to decreased abundance of gut bacteria with GABA-producing activities and/or with anti-inflammatory properties. To determine if the presence of depression in pwMS is associated with specific gut microbiome, gut-derived metabolites or peripheral blood immune profiles. The investigators will perform a cross-sectional study in clinically stable pwMS recruited at the John L. Trotter MS Center. The investigators will evaluate the presence of depression using the Quality of Life in Neurological Disorders (Neuro-Qol) depression scale, one of the 13 scales in the Neuro-Qol recently developed by the NIH using modern psychometric techniques and validated in pwMS.

A total of 120 pwMS will be recruited: 60 with and 60 without depression based on the Neuro-Qol depression scale. At the study visit each participant will be asked to provide a stool sample for microbiome analyses and a blood sample for peripheral blood immunophenotyping. Potential confounders will be collected and treated as covariates in the analyses. These include: 1) degree of disability (EDSS); 2) treatment with anti-depressants and DMTs; 3) a 4-days food diary to evaluate diet composition; 4) weight and height to calculate the BMI; 5) fatigue; 6) level of physical activity; 7) sleep quality.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Our overall hypothesis is that specific gut microbiome or gut-derived metabolites are associated with depression in pwMS. Mechanistically, the investigators further hypothesize that depression in pwMS is related to decreased abundance of gut bacteria with GABA-producing activities and/or with anti-inflammatory properties.

AIM 1. To determine if the presence of depression in pwMS is associated with specific gut microbiome, gut-derived metabolites or peripheral blood immune profiles.

The investigators will perform a cross-sectional study in clinically stable pwMS recruited at the John L. Trotter MS Center. The investigators will evaluate the presence of depression using the Quality of Life in Neurological Disorders (Neuro-Qol) depression scale, one of the 13 scales in the Neuro-Qol recently developed by the NIH using modern psychometric techniques and validated in pwMS. A total of 120 pwMS will be recruited: 60 with and 60 without depression based on the Neuro-Qol depression scale. At the study visit each participant will be asked to provide a stool sample for microbiome analyses and a blood sample for peripheral blood immunophenotyping. Potential confounders will be collected and treated as covariates in the analyses. These include: 1) degree of disability (EDSS); 2) treatment with anti-depressants and DMTs; 3) a 4-days food diary to evaluate diet composition; 4) the investigatorsight and height to calculate the BMI; 5) fatigue; 6) level of physical activity; 7) sleep quality.

AIM 1A. To determine if depression will correlate with specific gut microbiome or gut-derived metabolites profiles in pwMS.

Stool samples will be processed for microbiome sequencing and metabolome characterization.

AIM 1B. To determine if depression will correlate with a specific peripheral blood immune-inflammatory profile in pwMS.

A peripheral blood sample will be obtained from each participant to perform: 1) peripheral blood immune cell phenotyping to characterize the main immune cell subsets and their activation; 2) intracellular cytokine production to study cytokine production profiles of blood lymphocytes and monocytes.

AIM 2. To quantify GABA production in pwMS with or without depression and determine gut microbiome-immune system interaction in vitro.

In this aim the investigators will perform functional studies to evaluate the potential of gut microbiota from pwMS with or without depression to produce GABA and to modulate immune-inflammatory responses.

AIM 2A. To quantify GABA levels in whole stool, specific stool bacterial isolates and blood of pwMS with or without depression.

The investigators will evaluate GABA levels in the stool and blood of pwMS. In addition, the investigators will measure GABA production by Bacteroides ssp isolated from the gut microbiota of pwMS.

Aim 2B. To evaluate the effects of whole stool and specific bacterial species from pwMS on blood immune cell phenotype and cytokine production.

The investigators will test how whole gut microbiome or specific bacteria (identified in Aim 1 as associated with depression in pwMS) can modulate immune cell function. Peripheral blood mononuclear cells (PBMC) from healthy donors will be cultured in conditioning media from whole stool or bacteria of interest isolated from pwMS. PBMC phenotype and cytokine production after exposure in vitro will be characterized by flow cytometry.

Study Type

Observational

Enrollment (Actual)

51

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University in St Louis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with Multiple Sclerosis (MS)

Description

  1. Age ≥18 years
  2. Diagnosis of RRMS or progressive MS based on the 2017 revised McDonald criteria
  3. Untreated or on any of the MS DMTs as long as they have been stable clinically in the previous 3 months
  4. No history of antibiotic treatment in the 3 months prior to study visit and sample collection
  5. No other autoimmune diseases, chronic metabolic diseases (e.g. diabetes) or conditions (e.g. pregnancy) that would interfere with the parameters that we will be measuring in the stool and blood samples.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
With Neuro-QoL Depression scale T-score > 55
  1. Collection of demographic and clinical data (age, gender, BMI, ethnicity, age of onset, number of relapses).
  2. Administration of the Neuro-QoL depression scale
  3. Neurological exam to evaluate disability and calculate the EDSS score (ranging from 0 to 10)
  4. Neurological cognitive and functional assessments: a 9-hole Peg Test and 25-ft Timed Walk from the Multiple Sclerosis Functional Composite (MSFC); the Symbol Digit Modality Test (SDMT)
  5. Administration of the Fatigue Severity Scale (FSS)
  6. Collection of a 4-days food diary to evaluate diet composition of enrolled pwMS
  7. Administration of the Stanford 7-day Physical Activity Recall Scale (PAR)
  8. Evaluation of sleep quality by administration of the Neuro-QoL sleep disturbance scale
  9. Collection of a stool sample for gut microbiome and metabolome analyses
  10. Collection of a saliva sample for microbiome and metabolome analyses
Other: Neuro-QoL T-score determination
Neuro-Qol depression scale, using a T-score of 55 as a threshold
With Neuro-QoL Depression scale T-score < 55
  1. Collection of demographic and clinical data (age, gender, BMI, ethnicity, age of onset, number of relapses).
  2. Administration of the Neuro-QoL depression scale
  3. Neurological exam to evaluate disability and calculate the EDSS score (ranging from 0 to 10)
  4. Neurological cognitive and functional assessments: a 9-hole Peg Test and 25-ft Timed Walk from the Multiple Sclerosis Functional Composite (MSFC); the Symbol Digit Modality Test (SDMT)
  5. Administration of the Fatigue Severity Scale (FSS)
  6. Collection of a 4-days food diary to evaluate diet composition of enrolled pwMS
  7. Administration of the Stanford 7-day Physical Activity Recall Scale (PAR)
  8. Evaluation of sleep quality by administration of the Neuro-QoL sleep disturbance scale
  9. Collection of a stool sample for gut microbiome and metabolome analyses
  10. Collection of a saliva sample for microbiome and metabolome analyses
Other: Neuro-QoL T-score determination
Neuro-Qol depression scale, using a T-score of 55 as a threshold

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gut microbiome, gut-derived metabolites and peripheral blood immune profiles
Time Frame: 3 years
Gut microbiome will be characterized by metagenomic sequencing. Untargeted metabolome analysis performed by LC-MS. Peripheral blood phenotyping performed by flow cytometry analysis
3 years
GABA levels in whole stool, specific stool bacteria isolates and blood
Time Frame: 3 Years
GABA levels in whole stool measured by targeted LC-MS Effects of whole stool and specific bacterial species from people with MS with or without depression on blood immune cell phenotype and cytokine production measured by flow cytometry.
3 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

University of Texas
University of Connecticut

Investigators

  • Principal Investigator: Laura Piccio, MD, PhD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 27, 2022

Primary Completion (Actual)

October 29, 2024

Study Completion (Actual)

October 29, 2024

Study Registration Dates

First Submitted

May 17, 2022

First Submitted That Met QC Criteria

March 29, 2023

First Posted (Actual)

April 11, 2023

Study Record Updates

Last Update Posted (Estimated)

December 13, 2024

Last Update Submitted That Met QC Criteria

December 9, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202107067

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Will be determined based whether or not recruitment numbers will be sufficient to power outcome analyses.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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