Search

Introduction: Posttraumatic stress disorder (PTSD) is a debilitating disorder characterized by intrusive memories, avoidance, negative thoughts and moods, and heightened arousal. Many patients also report gastrointestinal symptoms. Cognitive behavioral therapy (CBT) is an evidence-based treatment approach for PTSD that successfully reduces symptoms. However, many patients still meet criteria for PTSD after treatment or continue to have symptoms indicating the need for new treatment strategies for PTSD. Patients with PTSD have a disrupted intestinal microbiome (i.e., dysbiosis) which can promote neuroinflammation; thus, modulation of the microbiome could be an alternative or adjunct treatment approach for PTSD. Methods: The current study was a 12-week, double-blind, placebo-controlled trial seeking to understand if CBT combined with a microbiota-modifying, prebiotic fiber intervention would beneficially impact clinical outcomes in veterans with PTSD (n = 70). This proof-of-concept, pilot trial was designed to assess: (1) the relationship between severity of PTSD symptoms and microbiota composition and SCFA levels (i.e., acetate, propionate, butyrate), (2) if CBT treatment with a concomitant prebiotic fiber intervention would beneficially impact clinical outcomes in veterans with PTSD, (3) evaluate the feasibility and acceptability of a prebiotic intervention as an adjunct treatment to CBT, and (4) assess the impact of treatment on the intestinal microbiota and stool SCFA (i.e., mechanism). Results: This study found that PTSD severity may be associated with reduced abundance of taxa capable of producing the SCFA propionate, and that a subset of individuals with PTSD may benefit from a microbiota-modifying prebiotic intervention. Conclusion: This study suggests that targeting the intestinal microbiome through prebiotic supplementation could represent a promising avenue for enhancing treatment outcomes in some individuals with PTSD. Clinical trial registration: https://clinicaltrials.gov/ , identifier NCT05424146. [ABSTRACT FROM AUTHOR]

Objective(s)Type I interferon (IFN-I) responses confer both protective and pathogenic effects in persistent virus infections. IFN-I diversity, stage of infection and tissue compartment may account for this dichotomy. The gut is a major site of early HIV-1 replication and microbial translocation, but the nature of the IFN-I response in this compartment remains unclear.DesignSamples were obtained from two IRB-approved cross-sectional studies. The first study included individuals with chronic, untreated HIV-1 infection (n = 24) and age/sex-balanced uninfected controls (n = 14). The second study included antiretroviral-treated, HIV-1-infected individuals (n = 15) and uninfected controls (n = 15).MethodsThe expression of 12 IFNα subtypes, IFNβ and antiviral IFN-stimulated genes (ISGs) were quantified in peripheral blood mononuclear cells (PBMCs) and colon biopsies using real-time PCR and next-generation sequencing. In untreated HIV-1-infected individuals, associations between IFN-I responses and gut HIV-1 RNA levels as well as previously established measures of colonic and systemic immunological indices were determined.ResultsIFNα1, IFNα2, IFNα4, IFNα5 and IFNα8 were upregulated in PBMCs during untreated chronic HIV-1 infection, but IFNβ was undetectable. By contrast, IFNβ was upregulated and all IFNα subtypes were downregulated in gut tissue. Gut ISG levels positively correlated with gut HIV-1 RNA and immune activation, microbial translocation and inflammation markers. Gut IFN-I responses were not significantly different between HIV-1-infected individuals on antiretroviral treatment and uninfected controls.ConclusionThe IFN-I response is compartmentalized during chronic untreated HIV-1 infection, with IFNβ being more predominant in the gut. Gut IFN-I responses are associated with immunopathogenesis, and viral replication is likely a major driver of this response.

HIV-infection is associated with dramatic changes in the intestinal mucosa. The impact of other viral pathogens is unclear.Eighty biopsies from left and right colon (n=63) and terminal ileum (n = 17) were collected from 19 HIV-infected and 22 HIV-uninfected subjects. Levels of cytomegalovirus (CMV) and Epstein Barr Virus (EBV) DNA were measured by droplet-digital (dd)PCR. Mucosal gene expression was measured via multiplex-assay. Microbiome analysis was performed using bacterial 16S-rDNA-pyrosequencing. The effect of CMV and EBV replication on the microbiome composition and mRNA-expression of selected cytokines (IL-6,IFN-γ,IL-1β, CCL2,IL-8 IFN-β1) was evaluated.Overall, CMV and EBV were detected in at least one intestinal site in 60.5% and 78.9% of subjects, respectively. HIV-infected individuals demonstrated less detectable CMV (p = 0.04); CMV was more frequently detected in terminal ileum than colon (p = 0.04). Detectable EBV was more frequent among HIV-infected (p = 0.05) without differences by intestinal site. The number of operational taxonomic units did not differ by CMV or EBV detection status. Among HIV-infected subjects, higher CMV was only associated with lower relative abundance of Actinobacteria in the ileum (p = 0.03). Presence of CMV was associated with up-regulated expression of all selected cytokines in the ileum (p

HIV-infection is associated with dramatic changes in the intestinal mucosa. The impact of other viral pathogens is unclear.Eighty biopsies from left and right colon (n=63) and terminal ileum (n = 17) were collected from 19 HIV-infected and 22 HIV-uninfected subjects. Levels of cytomegalovirus (CMV) and Epstein Barr Virus (EBV) DNA were measured by droplet-digital (dd)PCR. Mucosal gene expression was measured via multiplex-assay. Microbiome analysis was performed using bacterial 16S-rDNA-pyrosequencing. The effect of CMV and EBV replication on the microbiome composition and mRNA-expression of selected cytokines (IL-6,IFN-γ,IL-1β, CCL2,IL-8 IFN-β1) was evaluated.Overall, CMV and EBV were detected in at least one intestinal site in 60.5% and 78.9% of subjects, respectively. HIV-infected individuals demonstrated less detectable CMV (p = 0.04); CMV was more frequently detected in terminal ileum than colon (p = 0.04). Detectable EBV was more frequent among HIV-infected (p = 0.05) without differences by intestinal site. The number of operational taxonomic units did not differ by CMV or EBV detection status. Among HIV-infected subjects, higher CMV was only associated with lower relative abundance of Actinobacteria in the ileum (p = 0.03). Presence of CMV was associated with up-regulated expression of all selected cytokines in the ileum (p

The excessive use of alcohol is a global problem causing many adverse pathological health effects and a significant financial health care burden. This review addresses the effect of alcohol consumption [...]