Posttraumatic stress disorder is associated with altered gut microbiota that modulates cognitive performance in veterans with cirrhosis

Jasmohan S. Bajaj, Masoumeh Sikaroodi, Andrew Fagan, Douglas Heuman, Ho Chong Gilles, Edith A. Gavis, Michael Fuchs, Javier Gonzalez-Maeso, Shahzor Nizam, Patrick M. Gillevet, James B. Wade

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Posttraumatic stress disorder (PTSD) is associated with cirrhosis in veterans, and therapeutic results are suboptimal. An altered gut-liverbrain axis exists in cirrhosis due to hepatic encephalopathy (HE), but the added impact of PTSD is unclear. The aim of this study was to define linkages between gut microbiota and cognition in cirrhosis with/without PTSD. Cirrhotic veterans (with/without prior HE) underwent cognitive testing [PHES, inhibitory control test (ICT), and block design test (BDT)], serum lipopolysaccharide-binding protein (LBP) and stool collection for 16S rRNA microbiota composition, and predicted function analysis (PiCRUST). PTSD was diagnosed using DSM-V criteria. Correlation networks between microbiota and cognition were created. Patients with/without PTSD and with/without HE were compared. Ninety-three combat-exposed male veterans [ (58 yr, MELD 11, 34% HE, 31% combat-PTSD (42 no-HE/PTSD, 19 PTSDonly, 22 HE-only, 10 PTSD+HE)] were included. PTSD patients had similar demographics, alcohol history, MELD, but worse ICT/BDT, and higher antidepressant use and LBP levels. Microbial diversity was lower in PTSD (2.1 ± 0.5 vs. 2.5 ± 0.5, P = 0.03) but unaffected by alcohol/antidepressant use. PTSD (P = 0.02) and MELD (P = 0.001) predicted diversity on regression. PTSD patients showed higher pathobionts (Enterococcus and Escherichia/Shigella) and lower autochthonous genera belonging to Lachnospiraceaeae and Ruminococcaceae regardless of HE. Enterococcus was correlated with poor cognition, while the opposite was true for autochthonous taxa regardless of PTSD/HE. Escherichia/Shigella was only linked with poor cognition in PTSD patients. Gut-brain axis-associated microbiota functionality was altered in PTSD. In male cirrhotic veterans, combatrelated PTSD is associated with cognitive impairment, lower microbial diversity, higher pathobionts, and lower autochthonous taxa composition and altered gut-brain axis functionality compared with non-PTSD combat-exposed patients. Cognition was differentially linked to gut microbiota, which could represent a new therapeutic target.

Original languageEnglish
Pages (from-to)G5661-G669
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume317
Issue number5
DOIs
StatePublished - Nov 2019
Externally publishedYes

Keywords

  • Alcohol-use disorder
  • Correlation networks
  • Gut-brain axis
  • Hepatic encephalopathy

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