The Effect of a Butyrate-enhancing Synbiotic Intervention on Inflammatory Depression: a Stratified, Double-Blind, Randomized Controlled Trial

INTERVENTION: Group 1: Synbiotics‐group: Participants with inflammatory depression will receive an 8‐week synbiotic intervention. Three capsules are taken per day. After a screening visit, the following parameters are assessed before the intervention (T1) and after the intervention (T2), as well as at a follow‐up time point (T3): questionnaires and interviews regarding depressive symptoms, quality of life, stress, and motivation/energy; blood samples; stool samples; and computer tasks assessing motivational behavior. Group 2: Placebo‐group: Participants with inflammatory depression will receive an 8‐week placebo intervention. Three capsules are taken per day. After a screening visit, the following parameters are assessed before the intervention (T1) and after the intervention (T2), as well as at a follow‐up time point (T3): questionnaires and interviews regarding depressive symptoms, quality of life, stress, and motivation/energy; blood samples; stool samples; and computer tasks assessing motivational behavior. Group 3: Control group: Healthy participants who do not receive any intervention undergo only the screening and the first day of testing (T1). The same parameters as described above are recorded. CONDITION: ; F32 Depressive episode PRIMARY OUTCOME: Changes in atypical depressive symptoms, as measured by the SIGH‐ADS (Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement). This endpoint is assessed before the intervention, weekly during the intervention, and after the intervention (after 8 weeks), as well as at a follow‐up time point 12 weeks after baseline. SECONDARY OUTCOME: Differences in levels of SCFAs (short‐chain fatty acids) in plasma and fecal samples and pro‐inflammatory proteins (IL‐17A, IL‐6, TNF‐alpha) in plasma between depressed individuals and healthy controls, measured at baseline. ; Change of anhedonia symptoms as measured with the SHAPS‐D (Snaith‐Hamilton Pleasure Scale) and of quality of life as measured with the EQ‐5D‐5L (European Quality of Life Questionnaire 5 dimensions). Change in plasma concentrations of key cytokines (IL‐17A, IL‐6, TNF‐alpha). These endpoints are assessed before the intervention, after the intervention (after 8 weeks), as well as at follow‐up (12 weeks after baseline). INCLUSION CRITERIA: ‐ Ability to give consent ‐ BMI between 18‐40 kg/m² ‐ Willing and able to adhere to the provided diet on the days prior to testing ‐ A score of 10 or higher on the Hamilton Depression Rating Scale ‐ Exclusively for subjects with depression: o Inflammation: CRP of > 1mg/L o Presence of at least two out of the four following symptom categories: a) anhedonia b) increased appetite or weight c) increased sleep d) fatigue or leaden paralysis o Presence of a depressive episode, both first episode or an episode in the context of a known recurrent depressive disorder without psychotic symptoms o Need to be on stable medication for at least 4 weeks or not taking any medication for at least half a year prior to study start. A change in dosage of medication requires a 2‐week waiting period prior to participation.