Exaggerated inflammation in the body and brain is thought to play a role in the vulnerability to and aggravation and perpetuation of adverse consequences among those with posttraumatic stress disorder (PTSD). The proposed study begins the process of investigating the use of a natural immunoregulatory/anti-inflammatory probiotic, Lactobacillus rhamnosus GG (LGG; ATCC53103), to treat chronic symptoms associated with PTSD among Veterans. By looking at the impact of probiotic supplementation on biological signatures of increased inflammation, as reflected by biomarkers of inflammation, gut microbiota composition, intestinal permeability, stress response, decision making, and PTSD symptoms, this study may identify a novel intervention for the treatment of symptoms associated with this frequently occurring condition.
United States military Veterans from recent conflicts are coping with symptoms related to posttraumatic stress disorder (PTSD). Many Veterans are resistant to conventional health and mental health interventions (e.g., medication, psychotherapy), and often symptoms are not significantly improved by traditional treatments. Alternative treatment methods are needed. An underlying feature of PTSD is exaggerated inflammation, both peripherally and in the central nervous system, which is thought to play an important role in the vulnerability to, aggravation of, and perpetuation of adverse consequences of this condition. Therefore, an innovative intervention strategy would be the use of immunoregulatory/anti-inflammatory probiotics to reduce inflammation. In this study, the investigators will investigate the effects of an 8-week oral administration of an immunoregulatory probiotic, Lactobacillus rhamnosus GG (LGG; ATCC53103), a probiotic shown to have anti-inflammatory and immunoregulatory effects (i.e., decreases in C-reactive protein \[CRP\]). Project aims will be assessed using a longitudinal, double blind, randomized placebo-controlled design. After initial evaluation procedures to confirm PTSD diagnosis, 59 participants will be randomized to probiotic supplementation and 59 will be randomized to placebo supplementation. Primary Aim. Demonstrate the effects of LGG in a cohort of OEF/OIF Veterans with PTSD and Functional Bowel Disorders (FBD), including IBS, on plasma CRP concentrations (mechanistic, primary outcome), and PTSD symptom severity (clinical, exploratory). Additional biological signatures associated with this condition will be considered exploratory, including gut microbial community and intestinal permeability \[IP\]), other biological signatures of inflammation, as well as stress responsivity and decision making. Hypothesis 1.1. Those who receive LGG supplementation will respond with lower plasma levels of CRP as compared to those allocated to placebo. Exploratory Hypothesis 1.2. Those who receive LGG supplementation will respond with decreased PTSD symptoms (PCL-5), as compared to those allocated to placebo. Exploratory Hypothesis 1.3. Those who receive LGG supplementation will respond with increased abundance of LGG and community-level shifts (e.g.,increased alpha diversity) in the gut microbiota (measured using qRT-PCR and DNA sequencing of the 16S rRNA gene, respectively), decreases in IP (decreased fatty acid binding protein 215 and D-amino acid oxidase16), increases in plasma concentrations of anti-inflammatory biomarkers (IL-10, IL-4), decreases in additional plasma biomarkers of inflammation (IL-6, IL-8, IFNγ, IL- 1α, IL-1β, and IL-12p70), reduced stress response (biological and psychological) during and after Cyberball, and improved decision-making (measured by performance on the modified Iowa Gambling Test \[mIGT\]) as compared to those allocated to placebo. Exploratory Hypothesis 1.4. The effect of LGG supplementation on stress response, decision-making, and PTSD symptom severity is mediated by effects of LGG supplementation on the gut microbiota, intestinal permeability, and plasma biomarkers of inflammation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
383
See arm descriptions
See arm descriptions
VA Rocky Mountain Regional Center
Denver, Colorado, United States
Plasma concentration of C-reactive protein (CRP)
Blood biomarker of inflammation
Time frame: Change from basline to directly following the 8 week intervention
PTSD symptoms per the PTSD Checklist for DSM-5 (PCL-5)
PTSD symptoms
Time frame: Change from basline to directly following the 8 week intervention
Type and abundance measurement of gut microbiota
qRT-PCR and DNA sequencing of the 16S rRNA gene
Time frame: Change from basline to directly following the 8 week intervention
Plasma concentration of intestinal permeability
fatty acid binding protein 2 and D-amino acid oxidase
Time frame: Change from basline to directly following the 8 week intervention
Plasma concentration of inflammatory markers
IL-10, IL-4, IL-6, IL-8, IFNy, IL-1a, IL-1b, and IL-12p70
Time frame: Change from basline to directly following the 8 week intervention
Biological and psychological stress response
Cyberball
Time frame: Immediately post-intervention
Decision-making
Iowa Gambling Test
Time frame: Immediately post-intervention
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.