Han Ke, Ji Lei, Wang Chenliu, Shao Yang, Chen Changfeng, Liu Liangjie, Feng Mofan, Yang Fengping, Wu Xi, Li Xingwang, Xie Qinglian, He Lin, Shi Yi, He Guang, Dong Zaiquan, Yu Tao
Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory of Psychotic Disorders, Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China.
Front Genet. 2023 Jan 9;13:976814. doi: 10.3389/fgene.2022.976814. eCollection 2022.
The gut microbiome and host genetics are both associated with major depressive disorder (MDD); however, the molecular mechanisms among the associations are poorly understood, especially in the Asian, Chinese group. Our study applied linear discriminant analysis (LDA) effect size (LEfSe) and genome-wide association analysis in the cohort with both gut sequencing data and genomics data. We reported the different gut microbiota characteristics between MDD and control groups in the Chinese group and further constructed the association between host genetics and the gut microbiome. and were found more in the MDD group. We found significant differences in the ACE and Chao indexes of alpha diversity while no discrepancy in beta diversity. We found three associations between host genetics with microbiome features: beta diversity and rs6108 ( = 8.65 × 10), and rs77379751 ( = 8.56 × 10), and PWY-5913 and rs1775633082 ( = 4.54 × 10). A species of the genus was co-associated with the species of in an internetwork through four genes: , , , and , with a strict threshold ( < 5 × 10). Furthermore, our findings suggested that the gut microbiome diversity might affect microRNA expression in the brain and influenced and other spatially close genes afterward. These findings suggest new linkages between depression and gut microbiome in Asian, Chinese people, which might be mediated by genes and microRNA regulation in space distance.
肠道微生物群和宿主遗传学均与重度抑郁症（MDD）相关；然而，这些关联背后的分子机制却知之甚少，尤其是在亚洲的中国人群体中。我们的研究在一个同时拥有肠道测序数据和基因组数据的队列中应用了线性判别分析（LDA）效应大小（LEfSe）和全基因组关联分析。我们报告了中国人群体中MDD组和对照组之间不同的肠道微生物群特征，并进一步构建了宿主遗传学与肠道微生物群之间的关联。在MDD组中发现[具体物质1]和[具体物质2]更多。我们发现α多样性的ACE和Chao指数存在显著差异，而β多样性没有差异。我们发现宿主遗传学与微生物群特征之间存在三种关联：β多样性与rs6108（P = 8.65 × 10[具体指数]）、[具体物质3]与rs77379751（P = 8.56 × 10[具体指数]）以及PWY - 5913与rs1775633082（P = 4.54 × 10[具体指数]）。[某属的一种物种]通过四个基因：[基因1]、[基因2]、[基因3]和[基因4]，在一个网络中与[另一物种]共同相关，且有严格的阈值（P < 5 × 10[具体指数]）。此外，我们的研究结果表明，肠道微生物群多样性可能会影响大脑中的微小RNA表达，并随后影响[具体基因1]和其他空间上相邻的基因。这些发现揭示了亚洲中国人群中抑郁症与肠道微生物群之间的新联系，这可能是由基因和微小RNA在空间距离上的调控介导的。
