Effect of Probiotic Supplements on Oxidative Stress Biomarkers in First-Episode Bipolar Disorder Patients: A Randomized, Placebo-Controlled Trial.

Background: Currently no study has examined the effects of probiotic administration on the symptoms of anxiety, depression, and mania, as well as their correlations with the biomarkers of oxidative stress in patients with bipolar disorder (BPD). The aim of this study is to determine the effects of probiotic supplementation on plasma oxidative stress-related biomarkers and different domains of clinical symptom in patients suffering from BPD. Methods: Eighty first-episode drug-naive patients with BPD were recruited. The subjects were randomized to receive psychotropic drugs supplementing with either probiotic or placebo and scheduled to evaluate with follow-ups for clinical symptom improvements and changes in the oxidative stress biomarkers. The Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Young Mania Rating Scale were used to assess the clinical symptomatology. The panel of plasma oxidative stress biomarkers were determined by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) at baseline and for 3 months of follow-up, i.e., at post-treatment month 1, 2, and 3. Results: After 3 months of intervention, decreased levels of plasma lysophosphatidylcholines (LPCs) were found in both placebo and probiotic groups. However, six other oxidative stress biomarkers (i.e., creatine, inosine, hypoxanthine, choline, uric acid, allantoic acid) increased in BPD patients after the two types of therapies. In addition, a positive correlation between changes of LPC (18:0) and YMRS scale was found in BPD patients and this association only existed in the probiotic group. Additionally, the mania symptom greatly alleviated (pretreatment-posttreatment, odds ratio = 0.09, 95%CI = 0.01, 0.64, p= 0.016) in patients who received probiotic supplements as compared with the placebo group. Conclusion: The changes in plasma biomarkers of oxidative stress in patients with BPD have a potential to be trait-like markers, and serve as prognostic indexes for bipolar patients. Daily intakes of probiotics have advantageous effects on BPD patients with certain clinical symptoms, especially manic symptoms. The treatment may be a promising adjunctive therapeutic strategy for BPD patients in manic episode.