Gut Feeling: Understanding the Mechanisms Underlying the Antidepressant Properties of Probiotics (PROMEX)

Previous research has suggested that probiotics can improve depressive symptoms in patients with Major Depressive Disorder (MDD), particularly when used in addition to antidepressants. The aim of this exploratory pilot study is to improve the investigator's understanding of the mechanisms underlying these effects. This study will assess the effects of an 8-week double-blind placebo-controlled probiotic intervention on the gut microbiome, inflammatory marker levels, brain activity and neurotransmitter levels in patients with MDD and their relationship to changes in mood. This study will also recruit a group of demographically-matched healthy controls for gut microbiome comparison with the MDD group (non-interventional).

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Dietary supplement: Multi-strain probiotic; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 8AF
    • King's College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria for MDD participants:

• aged 18-55;
• currently in a depressive episode according to DSM-5 criteria, who are currently on antidepressant treatment but remain symptomatic (HAM-D17 score >13);
• on stable treatment regimen of an approved treatment for at least 6 weeks;
• non-smokers;
• for participants willing to take part in the neuroimaging component: right-handed, no contraindications, non-claustrophobic, weight <126kg;

Exclusion criteria for MDD participants:

• eating disorder, bipolar disorder, schizophrenia or psychotic symptoms;
• substance dependence in the past year, except for caffeine;
• active suicidal ideation;
• use of probiotic supplements in the past 2 weeks, or regular use of a probiotic;
• use of antibiotics in the past 12 weeks;
• history of allergic reaction to any of the components of BioKult;
• history of history of a systemic medical illness;
• current presence of significant GI problems or disease or history of major GI surgery;
• pregnancy or breastfeeding;
• following a dietary regimen unrepresentative of the general population (e.g. fasting or following a specific diet);
• regular/current use of antacids, proton pump inhibitors, laxatives, antidiarrheals;

Inclusion criteria for Healthy Volunteers:

• Aged 18-55;
• No current or historic presence of depression, other psychiatric disorder or substance dependence
• No history of a systemic medical illness;
• No family history of psychiatric disorder;
• Non-smoker;
• Not used probiotic supplements in the past 2 weeks, nor regular use of a probiotic;
• Not used antibiotics in the past 12 weeks;
• No current presence of gastrointestinal disease, or history of major GI surgery;
• No reported regular/current use of antacids, proton pump inhibitors, laxatives, antidiarrheals;
• pregnancy or breastfeeding;
• not currently following a dietary regimen or dietary restrictions unrepresentative of the general population (e.g. fasting or following a specific diet);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multi-strain probiotic "BioKult"; 4 capsules daily for 8 weeks	Dietary supplement: Multi-strain probiotic; The intervention in this study is a multi-strain probiotic which contains: Bacillus subtilis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Lactobacillus salivarius, Lactococcus lactis ssp. lactis, Streptococcus thermophilus. Each capsule contains minimum 2 billion live microorganisms per capsule, equivalent to 10 billion live microorganisms per gram.; Other Names: "BioKult"
Placebo Comparator: Placebo; 4 capsules daily for 8 weeks	Other: Placebo; Visually identical capsules in identical packaging containing no active bacteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gut microbiota in MDD	species diversity and abundance at the level of organisational taxonomic units (OTUs) will be measured with 16S ribosomal RNA (rRNA) sequencing	baseline
differences in gut microbiota between MDD and healthy volunteers	species diversity and abundance at the level of OTUs will be measured with 16SrRNA-based sequencing and compared between the two groups	baseline
gut microbiota changes in MDD following probiotic intervention and their correlation to change in depressive symptoms	species diversity and abundance at the level of OTUs will be measured with 16SrRNA-based sequencing and depressive symptoms will be measured with the Inventory of Depressive Symptomatology Self-Report (IDS-SR) and the Hamilton Depression Rating Scale (HAM-D17)	change from baseline to week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurotransmitters	levels of glutamate and gamma-aminobutyric acid (GABA) will be measured with Magnetic Resonance Imaging (MRS)	change from baseline to week 8
Blood	levels of tumor necrosis factor (TNF-a), interleukins IL-1β, IL-6, IL-17, and C-reactive protein (CRP) will be measured	change from baseline to week 8
Brain activity	measured with functional magnetic resonance imaging (fMRI)	change from baseline to week 8

Collaborators and Investigators

• Sponsor: King's College London
• Investigators: Principal Investigator: James M Stone, MBBS PhD FRCPsych, Institute of Psychiatry Psychology and Neuroscience, King's College London

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): June 29, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: March 22, 2019
• First Submitted That Met QC Criteria: March 27, 2019
• First Posted (Actual): March 28, 2019

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 29, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: depression; probiotic; microbiome; bacteria
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: PROMEX

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No