AUTHOR=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 

TITLE=The host genetics affects gut microbiome diversity in Chinese depressed patients

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.976814

DOI=10.3389/fgene.2022.976814

ISSN=1664-8021

ABSTRACT=<p>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. <italic>Actinobacteria</italic> and <italic>Pseudomonades</italic> 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 (<italic>p</italic> = 8.65 × 10<sup>–9</sup>), <italic>Actinobacteria</italic> and rs77379751 (<italic>p</italic> = 8.56 × 10<sup>–9</sup>), and PWY-5913 and rs1775633082 (<italic>p</italic> = 4.54 × 10<sup>–8</sup>). A species of the <italic>Romboutsia</italic> genus was co-associated with the species of <italic>Ruminococcus gnavus</italic> in an internetwork through four genes: <italic>METTL8</italic>, <italic>ITGB2</italic>, <italic>OTULIN</italic>, and <italic>PROSER3</italic>, with a strict threshold (<italic>p</italic> &lt; 5 × 10<sup>–4</sup>). Furthermore, our findings suggested that the gut microbiome diversity might affect microRNA expression in the brain and influenced <italic>SERPINA5</italic> 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.</p>