Supplementary Material for: Gut Microbiome Composition and Its Association with Sleep in Major Psychiatric Disorders

Introduction: Sleep disturbances are highly prevalent across most major psychiatric disorders. Alterations in the hypothalamic-pituitary-adrenal axis, neuroimmune mechanisms and circadian rhythm disturbances partially explain this connection. The gut microbiome is also suspected to play a role in sleep regulation and recent studies suggest that certain probiotics, prebiotics, synbiotics and fecal microbiome transplantation can improve sleep quality. Methods: We aimed to assess the relationship between gut-microbiota -composition, psychiatric disorders and sleep quality, in this cross-sectional, cross-disorder study. We recruited 103 participants, 63 patients with psychiatric disorders (Major Depressive Disorder n=31, Bipolar Disorder n=13, Psychotic Disorder n=19) along with 40 healthy controls. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The fecal microbiome was analyzed using 16S rRNA sequencing, and groups were compared based on alpha- and beta-diversity metrics as well as differentially abundant species and genera. Results: A transdiagnostic decrease in alpha diversity and differences in beta diversity indices were observed in psychiatric patients, compared to controls. Correlation analysis of diversity metrics and PSQI score showed no significance in the patient and control groups. However, three species, Ellagibacter isourolithinifaciens, Senegalimassilia faecalis and uncultured Blautia sp. and two genera, Senegalimassilia and uncultured Muribaculaceae genus were differentially abundant in psychiatric patients with good sleep quality (PSQI > 8), compared to poor sleep quality patients (PSQI ≤ 8). Conclusion: In conclusion, this study raises important questions about the interconnection of the gut microbiome and sleep disturbances.

引言：睡眠障碍在绝大多数重型精神障碍中均具有高患病率。下丘脑-垂体-肾上腺轴（hypothalamic-pituitary-adrenal axis）功能异常、神经免疫机制紊乱以及昼夜节律失调，可部分解释这一关联。肠道微生物组也被认为在睡眠调控中发挥作用，近期研究表明，特定的益生菌（probiotics）、益生元（prebiotics）、合生素（synbiotics）以及粪便微生物群移植（fecal microbiome transplantation）可改善睡眠质量。
方法：本研究为横断面、跨诊断研究，旨在探讨肠道微生物群组成、精神障碍与睡眠质量三者之间的关联。本研究共招募103名受试者，其中63名为精神障碍患者（重性抑郁症n=31、双相障碍n=13、精神病性障碍n=19），另40名为健康对照。采用匹兹堡睡眠质量指数（Pittsburgh Sleep Quality Index, PSQI）评估受试者的睡眠质量。通过16S rRNA测序分析粪便微生物组，并基于α多样性、β多样性指标以及差异丰度物种和属水平类群进行组间比较。
结果：与健康对照相比，精神障碍患者呈现出跨诊断性的α多样性降低以及β多样性指数差异。对多样性指标与PSQI评分进行相关性分析，结果在患者组与对照组中均未显示出统计学显著性。然而，与睡眠质量较差（PSQI ≤ 8）的患者相比，睡眠质量良好（PSQI > 8）的精神障碍患者体内存在3种差异丰度物种：埃拉吉杆菌（Ellagibacter isourolithinifaciens）、粪便塞内加尔芽孢杆菌（Senegalimassilia faecalis）以及未培养的布劳特氏菌（uncultured Blautia sp.），另有2个差异丰度菌属：塞内加尔芽孢杆菌属（Senegalimassilia）以及未培养的Muribaculaceae菌属（uncultured Muribaculaceae genus）。
结论：综上，本研究针对肠道微生物组与睡眠障碍之间的相互关联提出了重要的科学问题。