PROVIT: Supplementary Probiotic Treatment and Vitamin B7 in Depression-A Randomized Controlled Trial

Abstract

Gut microbiota are suspected to affect brain functions and behavior as well as lowering inflammation status. Therefore, an effect on depression has already been suggested by recent research. The aim of this randomized double-blind controlled trial was to evaluate the effect of probiotic treatment in depressed individuals. Within inpatient care, 82 currently depressed individuals were randomly assigned to either receive a multistrain probiotic plus biotin treatment or biotin plus placebo for 28 days. Clinical symptoms as well as gut microbiome were analyzed at the begin of the study, after one and after four weeks. After 16S rRNA analysis, microbiome samples were bioinformatically explored using QIIME, SPSS, R and Piphillin. Both groups improved significantly regarding psychiatric symptoms. Ruminococcus gauvreauii and Coprococcus 3 were more abundant and β-diversity was higher in the probiotics group after 28 days. KEGG-analysis showed elevated inflammation-regulatory and metabolic pathways in the intervention group. The elevated abundance of potentially beneficial bacteria after probiotic treatment allows speculations on the functionality of probiotic treatment in depressed individuals. Furthermore, the finding of upregulated vitamin B6 and B7 synthesis underlines the connection between the quality of diet, gut microbiota and mental health through the regulation of metabolic functions, anti-inflammatory and anti-apoptotic properties. Concluding, four-week probiotic plus biotin supplementation, in inpatient individuals with a major depressive disorder diagnosis, showed an overall beneficial effect of clinical treatment. However, probiotic intervention compared to placebo only differed in microbial diversity profile, not in clinical outcome measures.

Keywords: affective disorders; biotin; depression; gut-brain-axis; inflammation; microbiome; probiotics.

Figure 1

CONSORT Flow Diagram of the PROVIT study. Exclusion criteria consisted of acute suicidality, lack of consent, pregnancy or breastfeeding, severe active drug dependence (i.e., alcohol, benzodiazepines, morphine), other currently active severe cerebral organic diseases (e.g., epilepsy, brain tumor), severe skull- brain trauma/brain surgery in the past, known florid tumor disease, congenital/infantile mental disability, moderate/severe dementia, severe florid autoimmune diseases or current immunosuppression (e.g., lupus erythematosus, HIV, multiple sclerosis), antibiotic therapy within the last month, chronic laxative abuse, acute infectious diarrheal disease, regular intake of butyrate-containing or probiotic supplements in the last year, intake of (other) probiotics and prebiotics or butyrate preparations during the entire trial or within the last month and intake of antibiotics or prebiotics during the entire trial or within the last month.

Figure 2

Chao-1-diversity at the three time points in probiotic and placebo group.

Figure 3

Principal component analysis of participants of verum and placebo group at all three time points.