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).

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);