Potential causal association between gut microbiome and posttraumatic stress disorder

Abstract

Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR).

Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD's causal effects on the relative abundances of specific features of the gut microbiome.

Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability.

Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.

Fig. 1. Study overview of the two-sample Mendelian randomization for the potential causal association between gut microbiome and PTSD.

GM gut microbiome, PTSD post-traumatic stress disorder, SNP single nucleotide polymorphism, IV instrumental variables, IVW IVW, inverse variance weighted, RAPS robust adjusted profile score, MR-PRESSO MR Pleiotropy RESidual Sum and Outlier.

Fig. 2. Causal effect of the gut microbiome on PTSD in Freeze 2 datasets based on MR analyses.

From outside to inside, the P values of IVW, MR Egger, WMe, WMo, and SM are represented. PTSD post-traumatic stress disorder, IVW inverse variance weighted, WMe weighted median, WMo weighted mode, SM simple mode. MR mendelian randomization.

Fig. 3. The frost of positive MR results for the causal effects of the gut microbiome on PTSD in Freeze 2 datasets in MR analyses.

PTSD post-traumatic stress disorder, IVW inverse variance weighted, RAPS robust adjusted profile score.

Fig. 4. Causal effect of the gut microbiome on PTSD in FinnGen datasets based on MR analyses.

From outside to inside, the P values of IVW, MR Egger, WMe, WMo, and SM are represented. PTSD post-traumatic stress disorder, IVW inverse variance weighted, WMe weighted median, WMo weighted mode, SM simple mode. MR mendelian randomization.

Fig. 5. The frost of positive MR results for the causal effects of the gut microbiome on PTSD in FinnGen datasets in MR analyses.

PTSD post-traumatic stress disorder, IVW inverse variance weighted, RAPS robust adjusted profile score.

Fig. 6. The common bacterial traits in Freeze 2 datasets and FinnGen datasets for PTSD.

PTSD post-traumatic stress disorder.