O'Hare Michaela A, Rust Carlien, Malan-Müller Stefanie, Pirovano Walter, Lowry Christopher A, Ramaboli Matsepo, van den Heuvel Leigh L, Seedat Soraya, Hemmings Sian M J
Department of Biomedical Sciences, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Genes Brain Behav. 2025 Jun;24(3):e70025. doi: 10.1111/gbb.70025.
Posttraumatic stress disorder (PTSD) may develop following trauma exposure; however, not all trauma-exposed individuals develop PTSD, suggesting the presence of susceptibility and resilience factors. The gut microbiome and host genome, which are interconnected, have been implicated in the aetiology of PTSD. However, their interaction has yet to be investigated in a South African population. Using genome-wide genotype data and 16S rRNA (V4) gene amplicon sequencing data from 53 trauma-exposed controls and 74 PTSD cases, we observed no significant association between the host genome and summed abundance of Mitsuokella, Odoribacter, Catenibacterium and Olsenella, previously reported as associated with PTSD status in this cohort. However, PROM2 rs2278067 T-allele was significantly positively associated with the summed relative abundance of these genera, but only in individuals with PTSD and not trauma-exposed controls (p < 0.014). Polygenic risk scores generated using genome-wide association study summary statistics from the PGC-PTSD Overall Freeze 2 were not predictive of gut microbial composition in this cohort. These preliminary results suggest a potential role for the interaction between genetic variation and gut microbial composition in the context of PTSD, underscoring the need for further investigation.
创伤后应激障碍（PTSD）可能在经历创伤后发生；然而，并非所有经历创伤的个体都会患上PTSD，这表明存在易感性和恢复力因素。相互关联的肠道微生物群和宿主基因组与PTSD的病因有关。然而，它们之间的相互作用在南非人群中尚未得到研究。利用来自53名创伤暴露对照者和74名PTSD患者的全基因组基因型数据和16S rRNA（V4）基因扩增子测序数据，我们观察到宿主基因组与 Mitsuokella、Odoribacter、Catenibacterium 和 Olsenella 的总丰度之间无显著关联，此前该队列研究报道这些菌与PTSD状态有关。然而，PROM2 rs2278067的T等位基因与这些菌属的总相对丰度显著正相关，但仅在PTSD患者中存在这种相关性，而创伤暴露对照者中不存在（p < 0.014）。使用PGC-PTSD总体冻结2全基因组关联研究汇总统计数据生成的多基因风险评分不能预测该队列中的肠道微生物组成。这些初步结果表明，在PTSD背景下，基因变异与肠道微生物组成之间的相互作用可能发挥作用，强调了进一步研究的必要性。
