Gut Microbiota Characteristics In Patients With Bipolar Manic

BackgroundThe clinical manifestations of bipolar disorder are complex and have a variety of course evolvement.It is a disease with recurrent episodes throughout life,which will lead to impaired social function and reduced quality of life of patients.The etiology and pathological mechanism of bipolar disorder have not been fully clarified,and there is a lack of clear objective diagnostic indicators.As researchers learn more about the link between gut microbiota and the brain,the microbiota-gut-brain axis is gaining recognition.At present,most of the studies on the pathogenesis of bipolar disorder based on the microbiota-gutbrain axis are cross-sectional studies,and most of them focus on the depressive phase of bipolar disorder,while there are few reports on the characteristics of gut microbiota in patients with manic phase.ObjectivesThe purpose of this study was to compare the differences in gut microbiota characteristics between bipolar manic phase patients and healthy controls and the changes of gut microbiota after remission of mania symptoms.In addition,to explore the possibility of gut microbiota as a biomarker for the diagnosis and prognosis of bipolar disorder.MethodThirty-six patients with bipolar disorder manic phase hospitalized in the Second Affiliated Hospital of Xinxiang Medical University from October 2019 to January 2021 were included as the patient group,and 30 patients from their non-direct accompanying family members were recruited as the healthy control group during the same period.All subjects had clinical information collected by a psychiatrist to assess manic severity using the Young Mania Rating Scale(YMRS)and depression severity using the 17-item Hamilton Rating Scale for Depression(HRSD-17).Fecal samples of all subjects were collected within 48 hours of enrollment and stored in a refrigerator at-80℃ within 30 minutes.All patients received YMRS and HRSD-17 scores once a week,and fecal samples were collected again when YMRS < 6 and HRSD-17 < 7.After the sample collection was completed,the gut microbiota was sequenced and analyzed using the 16 Sr DNA sequencing method and the Miseq sequencer.Then,Qiime2 software was used to analyze the sequencing results to compare the differences of gut microbiota between the patient group and the healthy control group during the acute attack period and after remission,and to analyze the correlation between gut microbiota changes and clinical indicators.Results1.The abundance(P=0.047,P=0.040)and diversity(P=0.047,P=0.014)of gut microbiota in patients at the onset and remission stage were significantly higher than those in healthy control group.2.LEFSE analysis found that there were 71 signature species with significant differences in the patient group before and after treatment,including 35 enrichment species in the acute attack group and 36 enrichment species in the remission group(LDAScore > 2,P < 0.05).There was no significant difference in gut microbiota between the acute attack stage,remission stage and the healthy control group.3.There was no statistically significant linear correlation between different genera and YMRS scores.The course of the disease is positively correlated with the abundance of Monoglobus(r=0.546,P=0.001)、Barnesiella(r=0.449,P=0.007)、Corynebacterium(r=0.410,P=0.014)、Eisenbergiella(r=0.360,P=0.034)、Oscillospiraceae＿g＿uncultured(r=0.423,P=0.011)、Family＿XIII＿UCG＿001(r=0.356,P=0.036);BMI was negatively correlated with the abundance of Barnesiella(r=-0.382,P=0.023)、UCG＿002(r=-0.405,P=0.016)and UCG＿005(r=-0.343,P=0.043).Conclusion1.There were significant changes in the abundance and diversity of gut microbiota in bipolar manic disorder patients,which may be related to the occurrence of bipolar manic disorder.2.After treatment,there were statistically significant differences in gut microbiota between acute phase and remission phase,which may provide a new basis for the treatment of manic phase with bipolar disorder by adjusting gut microbiota.3.The changes of some gut microbiota were correlated with the course of disease and body mass index of patients with bipolar disorder manic phase,suggesting that the adjustment of gut microbiota may affect the course of disease and body mass index of patients with bipolar disorder manic phase.