Systematic review of probiotics as an adjuvant treatment for psychiatric disorders.

Introduction: Many psychiatric illnesses have been linked to the gut microbiome, with supplements such as probiotics showing some efficacy in alleviating the symptoms of some psychiatric illnesses. The aim of this review is to evaluate the current literature investigating the effects of adjuvant probiotic or synbiotic administration in combination with first-line treatments for psychiatric illnesses. Method: A systematic search of four databases was conducted using key terms related to treatments for psychiatric illnesses, the gut microbiome, and probiotics. All results were then evaluated based on specific eligibility criteria. Results: Eight studies met eligibility criteria and were analyzed for reported changes in outcome measures used to assess the symptoms of psychiatric illness and the tolerability of treatment. All Major Depressive Disorder (MDD) (n = 5) and Generalized Anxiety Disorder (GAD) (n = 1) studies found adjuvant probiotic or synbiotic treatment to be more efficacious in improving the symptoms of psychiatric illness than the first-line treatment alone or with placebo. The schizophrenia studies (n = 2) found adjuvant probiotic treatment to have no significant difference in clinical outcomes, but it was found to improve the tolerability of first-line antipsychotics. Discussion and conclusion: The findings of the studies included in this review suggest the use of adjuvant probiotic treatment with selective serotonin reuptake inhibitors (SSRIs) for MDD and GAD to be superior to SSRI treatment alone. Probiotic adjuvant treatment with antipsychotics could be beneficial for improving the tolerability of the antipsychotics, but these findings do not suggest that adjuvant probiotic treatment would result in improved clinical outcomes for symptoms of schizophrenia.

Versican promotes T helper 17 cytotoxic inflammation and impedes oligodendrocyte precursor cell remyelination.

Remyelination failure in multiple sclerosis (MS) contributes to progression of disability. The deficient repair results from neuroinflammation and deposition of inhibitors including chondroitin sulfate proteoglycans (CSPGs). Which CSPG member is repair-inhibitory or alters local inflammation to exacerbate injury is unknown. Here, we correlate high versican-V1 expression in MS lesions with deficient premyelinating oligodendrocytes, and highlight its selective upregulation amongst CSPG members in experimental autoimmune encephalomyelitis (EAE) lesions modeling MS. In culture, purified versican-V1 inhibits oligodendrocyte precursor cells (OPCs) and promotes T helper 17 (Th17) polarization. Versican-V1-exposed Th17 cells are particularly toxic to OPCs. In NG2CreER:MAPTmGFP mice illuminating newly formed GFP+ oligodendrocytes/myelin, difluorosamine (peracetylated,4,4-difluoro-N-acetylglucosamine) treatment from peak EAE reduces lesional versican-V1 and Th17 frequency, while enhancing GFP+ profiles. We suggest that lesion-elevated versican-V1 directly impedes OPCs while it indirectly inhibits remyelination through elevating local Th17 cytotoxic neuroinflammation. We propose CSPG-lowering drugs as potential dual pronged repair and immunomodulatory therapeutics for MS.