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

NCT ID: NCT03893162

Last Updated: 2022-06-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-01
• Study Completion Date: 2022-06-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Multi-strain probiotic "BioKult"

4 capsules daily for 8 weeks

Group Type: EXPERIMENTAL

Multi-strain probiotic

Intervention Type: 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.

Placebo

4 capsules daily for 8 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Visually identical capsules in identical packaging containing no active bacteria.

Interventions

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.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Visually identical capsules in identical packaging containing no active bacteria.

Intervention Type: OTHER

Other Intervention Names

"BioKult"

Eligibility Criteria

Inclusion Criteria

• 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;

• 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);

Exclusion Criteria

• 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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

King's College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James M Stone, MBBS PhD FRCPsych

Role: PRINCIPAL_INVESTIGATOR

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

Locations

King's College London

London, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39924003 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37314797 (View on PubMed)

Other Identifiers

PROMEX

Identifier Type: -

Identifier Source: org_study_id