The host genetics affects gut microbiome diversity in Chinese depressed patients

Ke Han; Lei Ji; Chenliu Wang; Yang Shao; Changfeng Chen; Liangjie Liu; Mofan Feng; Fengping Yang; Xi Wu; Xingwang Li; Qinglian Xie; Lin He; Yi Shi; Guang He; Zaiquan Dong; Tao Yu

doi:10.3389/fgene.2022.976814

The host genetics affects gut microbiome diversity in Chinese depressed patients

Front Genet. 2023 Jan 9:13:976814. doi: 10.3389/fgene.2022.976814. eCollection 2022.

Authors

Ke Han^{1

2}, Lei Ji^{1

2}, Chenliu Wang^{1

2}, Yang Shao³, Changfeng Chen⁴, Liangjie Liu^{1

2}, Mofan Feng^{1

2}, Fengping Yang^{1

2}, Xi Wu^{1

2}, Xingwang Li^{1

2}, Qinglian Xie⁵, Lin He^{1

2}, Yi Shi^{1

2}, Guang He^{1

2}, Zaiquan Dong⁶, Tao Yu^{1

7}

Affiliations

¹ Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China.
² Shanghai Key Laboratory of Psychotic Disorders, Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China.
³ Asbios (Tianjin) Biotechnology Co., Ltd., Tianjin, China.
⁴ School of Mental Health, Jining Medical University, Jining, China.
⁵ Out-patient Department of West China Hospital, Sichuan University, Chengdu, China.
⁶ Mental Health Center of West China Hospital, Sichuan University, Chengdu, China.
⁷ Shanghai Center for Women and Children's Health, Shanghai, China.

Abstract

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

Keywords: SERPINA5; beta diversity; depression; gut microbiome; microRNA.

Grants and funding

This project was supported by the National Key Research and Development Program (2016YFC0906400), the Innovation Funding in Shanghai (20JC1418600 and 18JC1413100), the National Natural Science Foundation of China (82071262 and 81671326), the Natural Science Foundation of Shanghai (20ZR1427200 and 20511101900), the Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), the Shanghai Leading Academic Discipline Project (B205), the Technology Department of Sichuan Province (2022YFS0350), the Capacity Building Planning Program for Shanghai Women and Children’s Health Service, and the collaborative Innovation Center Project Construction for Shanghai Women and Children’s Health.