The interaction between the gut microbiome and host genome in posttraumatic stress disorder

Trauma-and stressor-related disorders, disorders, such as posttraumatic stress disorder (PTSD), often develop following exposure to a traumatic event. However, not all individuals exposed to trauma develop these disorders, indicating that there must be a degree of susceptibility/resilience among individuals. This is partly explained by underlying genetic risk. Recently, alterations in gut microbial composition have been observed in relation to psychiatric disorders, which may explain some of the variation in susceptibility to these disorders. In addition, the host genome has been found to regulate certain aspects of the gut microbiome. There is much to be understood about the role of the gut microbiome, and genome, in human brain function and behaviour. By investigating the association between characteristics of the gut microbiome and host genetic components, this study aims to provide insight into the interaction between the gut microbiome and host genome in the context of PTSD. As part of the SHARED ROOTS project, genome-wide genotype data and 16S rRNA gene (V4) sequence gut microbiome data from 53 trauma-exposed controls and 74 PTSD patients of self-reported mixed-ancestry, will be used in an exploratory analysis to examine the association between host genotype of 143 gut microbiome-related SNPs and the summed relative abundance of 4 genus-level taxa (Mitsuokella, Odoribacter, Catenibacterium, and Olsenella). The total relative abundance of these taxa positively correlated with the severity of PTSD symptoms and was higher in PTSD participants compared to trauma-exposed controls. In addition, GWAS summary statistics from the Psychiatric Genomics Consortium were used to calculate the polygenic risk score (PRS) for PTSD to investigate if the genetic predisposition towards developing PTSD is associated with gut microbial composition. Exploratory analysis revealed associations between 10 SNPs and the summed relative abundance of the 4-genus level taxa (0.003 < p < 0.05). For the top 2 SNP associations (CNTNAP2 rs2710119 and PROM2 rs2278067), the summed relative abundance decreased with every copy of the CNTNAP2 rs2710119 T allele (p = 0.0025) and increased with every copy of the PROM2 rs2278067 T allele (p = 0.0081). In addition, rs2278067 interacted with PTSD case/control status (p < 0.0139) to influence the summed relative abundance, whereby the summed relative abundance increased with every copy of the rs2278067 T allele in PTSD cases, but not in controls. The polygenic risk for PTSD was not found to be predictive of gut microbial composition in this cohort. Our preliminary findings indicate a genetic association between host genetic components and gut microbial composition providing valuable insight into the complex relationship between the gut microbiome and host genome. These results should be replicated in a larger sample set.