The high prevalence of comorbid mental disorders (CMDs), such as anxiety and depression, in patients with inflammatory bowel disease (IBD) is well documented. The reported bidirectional relationship between the two conditions suggests a crucial role of a gut-brain axis in CMD development in patients with IBD. This study aimed to investigate a complex interplay between gut microbiota and host genetic variants relevant to the development of CMDs in IBD. Genome-wide variant data, gut metagenomic data, and/or anxiety/depression estimates were obtained from 507 patients with IBD and 75 healthy controls. A series of integrative analyses were performed, profiling gut microbial diversity, microbial abundance, polygenic risk score, microbial quantitative trait locus (mbQTL), and microbial IBD-risk score. Patients with IBD had significantly lower gut microbial alpha diversity than controls, particularly those with CMD. Beta diversity revealed that a large fraction of IBD-associated taxa contributing to the top principal component were potentially associated with CMD risk. We identified 146 significantly differentially abundant taxa (DATs) between IBD patients and controls, and 48 DATs between CMD-free and CMD-affected IBD patients, with the majority showing consistent changes in abundance between IBD and CMD. Microbial IBD-risk scores, developed to estimate the degree of microbial IBD-specific burden in each individual, supported a significant enrichment of IBD-risk signatures in CMD-affected patients. Additionally, we found an IBD-risk mbQTL for an IBD/CMD-associated DAT, implicating an interplay between IBD-risk variants and gut dysbiosis in the development of both IBD and CMD. Collectively, IBD-associated gut dysbiosis predominantly confers risk of CMD in IBD patients partially through genetic variant-mediated regulation.

中文翻译：

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炎症性肠病的肠道微生物和人类遗传特征会增加合并精神障碍的风险

炎症性肠病 (IBD) 患者中焦虑和抑郁等共病精神障碍 (CMD) 的患病率很高，这是有据可查的。据报道，这两种情况之间的双向关系表明肠-脑轴在 IBD 患者 CMD 发展中发挥着至关重要的作用。本研究旨在调查肠道微生物群与宿主遗传变异之间复杂的相互作用，这些变异与 IBD 中 CMD 的发展相关。从 507 名 IBD 患者和 75 名健康对照中获得全基因组变异数据、肠道宏基因组数据和/或焦虑/抑郁估计。进行了一系列综合分析，分析了肠道微生物多样性、微生物丰度、多基因风险评分、微生物数量性状基因座 (mbQTL) 和微生物 IBD 风险评分。 IBD 患者的肠道微生物 α 多样性显着低于对照组，尤其是 CMD 患者。 Beta 多样性表明，IBD 相关类群中大部分构成顶部主成分的类群可能与 CMD 风险相关。我们在 IBD 患者和对照之间确定了 146 个丰度显着差异的类群 (DAT)，在无 CMD 和受 CMD 影响的 IBD 患者之间确定了 48 个 DAT，其中大多数在 IBD 和 CMD 之间表现出一致的丰度变化。微生物 IBD 风险评分是为了估计每个人的微生物 IBD 特异性负担程度而开发的，支持 CMD 患者中 IBD 风险特征的显着丰富。此外，我们还发现了 IBD/CMD 相关 DAT 的 IBD 风险 mbQTL，这表明 IBD 风险变异与肠道菌群失调在 IBD 和 CMD 的发展过程中存在相互作用。总的来说，IBD 相关的肠道菌群失调主要通过遗传变异介导的调节，导致 IBD 患者患 CMD 的风险。