STUDY QUESTION How does the gut bacteriome differ based on mood disorders (MDs) in women with polycystic ovary syndrome (PCOS), and how can the gut bacteriome contribute to the associations between these two conditions? SUMMARY ANSWER Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha diversity and a significantly lower abundance of Butyricicoccus compared to women with PCOS but without MDs. WHAT IS KNOWN ALREADY Women with PCOS have a 4- to 5-fold higher risk of having MDs compared to women without PCOS. The gut bacteriome has been suggested to influence the pathophysiology of both PCOS and MDs. STUDY DESIGN, SIZE, DURATION This population-based cohort study was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), which includes all women born in Northern Finland in 1966. Women with PCOS who donated a stool sample at age 46 years (n = 102) and two BMI-matched controls for each case (n = 205), who also responded properly to the MD criteria scales, were included. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 102 women with PCOS and 205 age- and BMI-matched women without PCOS were included. Based on the validated MD criteria, the subjects were categorized into MD or no-MD groups, resulting in the following subgroups: PCOS no-MD (n = 84), PCOS MD (n = 18), control no-MD (n = 180), and control MD (n = 25). Clinical characteristics were assessed at age 31 years and age 46 years, and stool samples were collected from the women at age 46 years, followed by the gut bacteriome analysis using 16 s rRNA sequencing. Alpha diversity was assessed using observed features and Shannon’s index, with a focus on genera, and beta diversity was characterized using principal components analysis (PCA) with Bray–Curtis Dissimilarity at the genus level. Associations between the gut bacteriome and PCOS-related clinical features were explored by Spearman’s correlation coefficient. A P-value for multiple testing was adjusted with the Benjamini–Hochberg false discovery rate (FDR) method. MAIN RESULTS AND THE ROLE OF CHANCE We observed changes in the gut bacteriome associated with MDs, irrespective of whether the women also had PCOS. Similarly, PCOS MD cases showed a lower alpha diversity (Observed feature, PCOS no-MD, median 272; PCOS MD, median 208, FDR = 0.01; Shannon, PCOS no-MD, median 5.95; PCOS MD, median 5.57, FDR = 0.01) but also a lower abundance of Butyricicoccus (log-fold changeAnalysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC)=−0.90, FDRANCOM-BC=0.04) compared to PCOS no-MD cases. In contrast, in the controls, the gut bacteriome did not differ based on MDs. Furthermore, in the PCOS group, Sutterella showed positive correlations with PCOS-related clinical parameters linked to obesity (BMI, r2=0.31, FDR = 0.01; waist circumference, r2=0.29, FDR = 0.02), glucose metabolism (fasting glucose, r2=0.46, FDR < 0.001; fasting insulin, r2=0.24, FDR = 0.05), and gut barrier integrity (zonulin, r2=0.25, FDR = 0.03). LIMITATIONS, REASONS FOR CAUTION Although this was the first study to assess the link between the gut bacteriome and MDs in PCOS and included the largest PCOS dataset for the gut microbiome analysis, the number of subjects stratified by the presence of MDs was limited when contrasted with previous studies that focused on MDs in a non-selected population. WIDER IMPLICATIONS OF THE FINDINGS The main finding is that gut bacteriome is associated with MDs irrespective of the PCOS status, but PCOS may also modulate further the connection between the gut bacteriome and MDs. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement (MATER, No. 813707), the Academy of Finland (project grants 315921, 321763, 336449), the Sigrid Jusélius Foundation, Novo Nordisk Foundation (NNF21OC0070372), grant numbers PID2021-12728OB-100 (Endo-Map) and CNS2022-135999 (ROSY) funded by MCIN/AEI/10.13039/501100011033 and ERFD A Way of Making Europe. The study was also supported by EU QLG1-CT-2000-01643 (EUROBLCS) (E51560), NorFA (731, 20056, 30167), USA/NIH 2000 G DF682 (50945), the Estonian Research Council (PRG1076, PRG1414), EMBO Installation (3573), and Horizon 2020 Innovation Grant (ERIN, No. EU952516). The funders did not participate in any process of the study. We have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

中文翻译：

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多囊卵巢综合症女性的肠道细菌组和情绪障碍

研究问题 多囊卵巢综合征 (PCOS) 女性的肠道细菌组因情绪障碍 (MD) 有何不同，肠道细菌组如何影响这两种疾病之间的关联？摘要答案 与患有 PCOS 但没有 MD 的女性相比，同时患有 MD 的 PCOS 女性表现出独特的肠道细菌组，α 多样性降低，丁酸球菌丰度显着降低。已知信息 患有 PCOS 的女性患 MD 的风险比未患 PCOS 的女性高 4 至 5 倍。肠道细菌组被认为影响 PCOS 和 MD 的病理生理学。研究设计、规模、持续时间 这项基于人群的队列研究源自 1966 年芬兰北部出生队列 (NFBC1966)，其中包括 1966 年在芬兰北部出生的所有女性。 46 岁时捐赠粪便样本的 PCOS 女性（n = 102）和每个病例的两个 BMI 匹配对照（n = 205），他们也对 MD 标准量表做出了正确的反应。参与者/材料、环境、方法 总共包括 102 名患有 PCOS 的女性和 205 名年龄和 BMI 匹配的非 PCOS 女性。根据经过验证的 MD 标准，受试者被分为 MD 组或无 MD 组，从而产生以下亚组：PCOS 无 MD (n = 84)、PCOS MD (n = 18)、对照无 MD (n = 180) 和对照 MD (n = 25)。对 31 岁和 46 岁时的临床特征进行评估，并在 46 岁时采集女性的粪便样本，然后使用 16 s rRNA 测序进行肠道细菌组分析。使用观察到的特征和香农指数评估α多样性，重点关注属，并使用主成分分析（PCA）和属水平的布雷-柯蒂斯相异性来表征β多样性。通过 Spearman 相关系数探讨了肠道细菌组与 PCOS 相关临床特征之间的关联。使用 Benjamini-Hochberg 错误发现率 (FDR) 方法调整多重测试的 P 值。主要结果和机会的作用 我们观察到与 MD 相关的肠道细菌组的变化，无论女性是否也患有 PCOS。同样，PCOS MD 病例显示出较低的 α 多样性（观察特征，PCOS no-MD，中位数 272；PCOS MD，中位数 208，FDR = 0.01；Shannon，PCOS no-MD，中位数 5.95；PCOS MD，中位数 5.57，FDR = 0.01），但与 PCOS 无 MD 病例相比，丁酸球菌丰度也较低（偏差校正微生物组成分的对数倍变化分析（ANCOM-BC）=−0.90，FDRANCOM-BC=0.04）。相比之下，在对照组中，肠道细菌组并没有根据 MD 的不同而有所不同。此外，在 PCOS 组中，Sutterella 与与肥胖相关的 PCOS 相关临床参数（BMI，r2=0.31，FDR = 0.01；腰围，r2=0.29，FDR = 0.02）、葡萄糖代谢（空腹血糖，r2）呈正相关。 = 0.46，FDR < 0.001，r2 = 0.24，FDR = 0.05），和肠道屏障完整性（连蛋白，r2=0.25，FDR=0.03）。尽管这是第一项评估 PCOS 中肠道细菌组与 MD 之间联系的研究，并且包含了用于肠道微生物组分析的最大 PCOS 数据集，但与 MD 的存在分层的受试者数量相比，还是有限的。之前的研究重点关注非选定人群中的MD。研究结果的更广泛意义 主要发现是，无论 PCOS 状态如何，肠道细菌组都与 MD 相关，但 PCOS 也可能进一步调节肠道细菌组和 MD 之间的联系。研究经费/竞争利益 这项研究由芬兰科学院根据 Marie Sklodowska-Curie 赠款协议（MATER，编号 813707）资助的欧盟地平线 2020 研究与创新计划（项目赠款 315921、321763、336449） ）、Sigrid Jusélius 基金会、诺和诺德基金会 (NNF21OC0070372)，拨款号为 PID2021-12728OB-100 (Endo-Map) 和 CNS2022-135999 (ROSY)，由 MCIN/AEI/10.13039/501100011033 和 ERFD A Way of Making Europe 资助。该研究还得到了欧盟 QLG1-CT-2000-01643 (EUROBLCS) (E51560)、NorFA (731, 20056, 30167)、USA/NIH 2000 G DF682 (50945)、爱沙尼亚研究委员会 (PRG1076、PRG1414)、 EMBO 安装 (3573) 和地平线 2020 创新补助金（ERIN，编号 EU952516）。资助者没有参与该研究的任何过程。我们没有需要声明的利益冲突。试用注册号 不适用。