摘要

目的1.对比双相障碍躁狂相患者与健康对照组肠道菌群特征的差异。2.探究躁狂症状缓解后肠道菌群的改变。

方法 纳入2019年10月-2021年1月新乡医学院第二附属医院36例双相障碍躁狂相住院患者为患者组，同期从住院患者非直系陪护家属中招募30例为健康对照组。所有受试者由精神科医生进行临床信息采集，运用Young躁狂评定量表（YMRS）评定躁狂严重程度，利用17项Hamilton抑郁量表（HRSD-17）评定抑郁严重程度。于入组48小时内收集所有受试者的大便标本，并于30分钟内保存在-80℃冰箱内。所有患者每周进行一次YMRS和HRSD-17评分，待YMRS＜6且HRSD-17＜7时，再次收集患者的大便样本。待样本收集完成后，使用Miseq测序仪并运用16S rDNA测序法进行肠道菌群测序分析。然后，采用QIIME2软件对测序

结果进行分析，比较患者组急性发作期和缓解后肠道菌群与健康对照组的差异。

结果1.发作期和缓解期的患者肠道菌群丰度（P=0.047，P=0.040）和多样性（P=0.047，P=0.014）均高于与健康对照组。2.LEfSe分析发现在治疗前后患者组共有71种差异显著的标志性物种，急性发作期患者组富集的菌群有35种，缓解期患者组富集的菌群有36种（LDA score＞2，P＜0.05），未发现急性发作期、缓解期患者肠道菌群与健康对照组有显著差异的菌群。

结论1.本研究

结果表明双相障碍躁狂相患者的肠道菌群丰度和多样性较对照组增加，可能与双相障碍躁狂相的发生有关。2.经过治疗后，急性期和缓解期肠道菌群存在差异群落，可能为通过调整肠道菌群治疗双相障碍燥狂相提供新的依据。

关键词：双相障碍；肠道菌群；微生物-肠-脑轴；16S rRNA测序

ABSTRACT

Objectives The 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. Method Thirty-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 16SrDNA 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.

Results 1.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.

Conclusion   1.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.

Key words: [Key words] Bipolar disorder; Gut microbiota; Microbiota-gut-brain axis; 16S rRNA sequencing