Gut Feeling: Understanding the Mechanisms Underlying the Antidepressant Properties of Probiotics

NCT03893162 | Completed

• 1 other identifier: PROMEX
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Major Depressive Disorder

Keywords

probiotic; depression; microbiome; bacteria

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Neurotransmitters

  change from baseline to week 8

• Blood

  change from baseline to week 8

• Brain activity

  change from baseline to week 8

Study Arms (2)

Multi-strain probiotic "BioKult"

EXPERIMENTAL

4 capsules daily for 8 weeks

Dietary Supplement: Multi-strain probiotic

Placebo

PLACEBO COMPARATOR

4 capsules daily for 8 weeks

Other: Placebo

Interventions

Multi-strain probiotic DIETARY_SUPPLEMENT

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.

Also known as: "BioKult"

Multi-strain probiotic "BioKult"

Placebo OTHER

Visually identical capsules in identical packaging containing no active bacteria.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• King's College London: lead

Study Sites (1)

King's College London

London, SE5 8AF, United Kingdom

Location

Related Publications (2)

• Nikolova VL, Cleare AJ, Young AH, Stone JM. Exploring the mechanisms of action of probiotics in depression: Results from a randomized controlled pilot trial. J Affect Disord. 2025 May 1;376:241-250. doi: 10.1016/j.jad.2025.01.153. Epub 2025 Feb 7.

  PMID: 39924003 DERIVED

• Nikolova VL, Cleare AJ, Young AH, Stone JM. Acceptability, Tolerability, and Estimates of Putative Treatment Effects of Probiotics as Adjunctive Treatment in Patients With Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2023 Aug 1;80(8):842-847. doi: 10.1001/jamapsychiatry.2023.1817.

  PMID: 37314797 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• James M Stone, MBBS PhD FRCPsych

  Institute of Psychiatry Psychology and Neuroscience, King's College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2019
• First Posted: March 28, 2019
• Study Start: July 1, 2019
• Primary Completion: June 29, 2022
• Study Completion: June 30, 2022
• Last Updated: June 30, 2022

Record last verified: 2021-09

Locations

GB (1)