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已发表论文
产后抑郁症中肠道微生物与宿主基因的探究：孟德尔随机化与转录组学分析
Authors Cong T, Liu J, Yuan L, Chu Z
Received 18 April 2025
Accepted for publication 23 October 2025
Published 27 November 2025 Volume 2025:17 Pages 4981—4994
DOI https://doi.org/10.2147/IJWH.S535357
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Matteo Frigerio
Ting Cong,1,2,* Jing Liu,3,* Li Yuan,1,2 Zhenchen Chu4
1Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China; 2Shandong Provincial Key Medical and Health Laboratory of Anesthesia and Brain Function, Qingdao, Shandong, 266000, People’s Republic of China; 3Department of Psychiatry, Dalian Seventh People’s Hospital, Dalian, Liaoning, 116023, People’s Republic of China; 4Department of Orthopedics, Qingdao Municipal Hospital, Qingdao, Shandong, 266011, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Li Yuan, Department of Anesthesiology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Shinan District, Qingdao, Shandong, 266000, People’s Republic of China, Email l1861807210@163.com Zhenchen Chu, Department of Orthopedics, Qingdao Municipal Hospital, No. 5 Donghai Middle Road, Shinan District, Qingdao, Shandong, 266011, People’s Republic of China, Email czc8832754@163.com
Purpose: To suggest a potential causal role of gut microbiota in Postpartum depression (PPD) and identify susceptible microbiota-host genes.
Patients and Methods: The two-sample Mendelian randomization (MR) study was carried out with the genome-wide association studies (GWAS) data of 196 gut microbial taxa and PPD. Causal relationships were evaluated with inverse variance weighted (IVW), MR‒Egger, weighted mode, and weighted median approaches. Cochran’s Q test, the MR‒Egger intercept test, the MR-PRESSO test, and leave-one-out analysis were performed for assessing pleiotropy and heterogeneity. Additionally, false discovery rate (FDR) correction was completed via q-value method. A microarray dataset was carried out to identify susceptible microbiota-host genes.
Results: IVW suggested that the family Veillonellaceae [odds ratio (OR) = 0.82, 95% confidence interval (CI) = 0.71– 0.94, p = 0.004, q = 0.030] decreased the PPD risk, but the class Alphaproteobacteria (OR = 1.22, 95% CI = 1.01– 1.47, p = 0.041, q = 0.074) and the genus Family XIII AD3011 group (OR = 1.24, 95% CI = 1.04– 1.48, p = 0.019, q = 0.065) increased the incidence of PPD. Additionally, we extracted SNP-related genes from the Family XIII AD3011 group and identified four gut microbe-host genes (AQP9, ALDH1A2, DGUOK, and STAMBP) in combination with the transcriptome dataset GSE45603.
Conclusion: The findings support the genetically predicted causal relationship of gut microbiota with PPD and identify susceptible microbiota-host genes as potential therapeutic targets or diagnostic biomarkers, providing new insights into the prevention and intervention of PPD.
Keywords: postpartum depression, gut microbiota, Mendelian randomization, gut microbe‒host genes, transcriptome dataset
1Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China; 2Shandong Provincial Key Medical and Health Laboratory of Anesthesia and Brain Function, Qingdao, Shandong, 266000, People’s Republic of China; 3Department of Psychiatry, Dalian Seventh People’s Hospital, Dalian, Liaoning, 116023, People’s Republic of China; 4Department of Orthopedics, Qingdao Municipal Hospital, Qingdao, Shandong, 266011, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Li Yuan, Department of Anesthesiology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Shinan District, Qingdao, Shandong, 266000, People’s Republic of China, Email l1861807210@163.com Zhenchen Chu, Department of Orthopedics, Qingdao Municipal Hospital, No. 5 Donghai Middle Road, Shinan District, Qingdao, Shandong, 266011, People’s Republic of China, Email czc8832754@163.com
Purpose: To suggest a potential causal role of gut microbiota in Postpartum depression (PPD) and identify susceptible microbiota-host genes.
Patients and Methods: The two-sample Mendelian randomization (MR) study was carried out with the genome-wide association studies (GWAS) data of 196 gut microbial taxa and PPD. Causal relationships were evaluated with inverse variance weighted (IVW), MR‒Egger, weighted mode, and weighted median approaches. Cochran’s Q test, the MR‒Egger intercept test, the MR-PRESSO test, and leave-one-out analysis were performed for assessing pleiotropy and heterogeneity. Additionally, false discovery rate (FDR) correction was completed via q-value method. A microarray dataset was carried out to identify susceptible microbiota-host genes.
Results: IVW suggested that the family Veillonellaceae [odds ratio (OR) = 0.82, 95% confidence interval (CI) = 0.71– 0.94, p = 0.004, q = 0.030] decreased the PPD risk, but the class Alphaproteobacteria (OR = 1.22, 95% CI = 1.01– 1.47, p = 0.041, q = 0.074) and the genus Family XIII AD3011 group (OR = 1.24, 95% CI = 1.04– 1.48, p = 0.019, q = 0.065) increased the incidence of PPD. Additionally, we extracted SNP-related genes from the Family XIII AD3011 group and identified four gut microbe-host genes (AQP9, ALDH1A2, DGUOK, and STAMBP) in combination with the transcriptome dataset GSE45603.
Conclusion: The findings support the genetically predicted causal relationship of gut microbiota with PPD and identify susceptible microbiota-host genes as potential therapeutic targets or diagnostic biomarkers, providing new insights into the prevention and intervention of PPD.
Keywords: postpartum depression, gut microbiota, Mendelian randomization, gut microbe‒host genes, transcriptome dataset