BACKGROUND AND AIMS: Mood and cognition alterations play a role in the motivation for alcohol-drinking. Lipopolysaccharides are known to stimulate inflammation that was shown to induce mood and cognitive changes in rodents and humans. Enhanced intestinal permeability and elevated blood LPS characterize alcohol-dependent mice. However, no data have been published in non-cirrhotic humans. Our first goal was to test whether intestinal permeability, blood LPS and cytokines are increased in non-cirrhotic alcohol-dependent subjects before withdrawal and if they recover after withdrawal. Our second goal was to test correlations between these biochemical and the behavioral variables to explore the possibility of a role for a gut-brain interaction in the development of alcohol-dependence. METHODS: Forty alcohol-dependent-subjects hospitalized for a 3-week detoxification program were tested at onset (T1) and end (T2) of withdrawal and compared for biological and behavioral markers with 16 healthy subjects. Participants were assessed for gut permeability, systemic inflammation (LPS, TNFα, IL-6, IL-10, hsCRP) and for depression, anxiety, alcohol-craving and selective attention. RESULTS: Intestinal permeability and LPS were largely increased in alcohol-dependent subjects at T1 but recovered completely at T2. A low-grade inflammation was observed at T1 that partially decreased during withdrawal. At T1, pro-inflammatory cytokines were positively correlated with craving. At T2 however, the anti-inflammatory cytokine IL-10 was negatively correlated with depression, anxiety and craving. CONCLUSION: Leaky gut and inflammation were observed in non-cirrhotic alcohol-dependent subjects and inflammation was correlated to depression and alcohol-craving. This suggests that the gut-brain axis may play a role in the pathogenesis of alcohol-dependence.
BACKGROUND AND AIMS: Mood and cognition alterations play a role in the motivation for alcohol-drinking. Lipopolysaccharides are known to stimulate inflammation that was shown to induce mood and cognitive changes in rodents and humans. Enhanced intestinal permeability and elevated blood LPS characterize alcohol-dependent mice. However, no data have been published in non-cirrhotic humans. Our first goal was to test whether intestinal permeability, blood LPS and cytokines are increased in non-cirrhotic alcohol-dependent subjects before withdrawal and if they recover after withdrawal. Our second goal was to test correlations between these biochemical and the behavioral variables to explore the possibility of a role for a gut-brain interaction in the development of alcohol-dependence. METHODS: Forty alcohol-dependent-subjects hospitalized for a 3-week detoxification program were tested at onset (T1) and end (T2) of withdrawal and compared for biological and behavioral markers with 16 healthy subjects. Participants were assessed for gut permeability, systemic inflammation (LPS, TNFα, IL-6, IL-10, hsCRP) and for depression, anxiety, alcohol-craving and selective attention. RESULTS: Intestinal permeability and LPS were largely increased in alcohol-dependent subjects at T1 but recovered completely at T2. A low-grade inflammation was observed at T1 that partially decreased during withdrawal. At T1, pro-inflammatory cytokines were positively correlated with craving. At T2 however, the anti-inflammatory cytokine IL-10 was negatively correlated with depression, anxiety and craving. CONCLUSION: Leaky gut and inflammation were observed in non-cirrhotic alcohol-dependent subjects and inflammation was correlated to depression and alcohol-craving. This suggests that the gut-brain axis may play a role in the pathogenesis of alcohol-dependence.
Authors: Sonja Lang; Yi Duan; Jinyuan Liu; Manolito G Torralba; Claire Kuelbs; Meritxell Ventura-Cots; Juan G Abraldes; Francisco Bosques-Padilla; Elizabeth C Verna; Robert S Brown; Victor Vargas; Jose Altamirano; Juan Caballería; Debbie Shawcross; Michael R Lucey; Alexandre Louvet; Philippe Mathurin; Guadalupe Garcia-Tsao; Samuel B Ho; Xin M Tu; Ramon Bataller; Peter Stärkel; Derrick E Fouts; Bernd Schnabl Journal: Hepatology Date: 2019-08-20 Impact factor: 17.425
Authors: Anny Gano; Ricardo M Pautassi; Tamara L Doremus-Fitzwater; Thaddeus M Barney; Andrew S Vore; Terrence Deak Journal: Exp Biol Med (Maywood) Date: 2019-02-26
Authors: Sarah L Hagerty; Jarrod M Ellingson; Timothy B Helmuth; L Cinnamon Bidwell; Kent E Hutchison; Angela D Bryan Journal: Perspect Psychol Sci Date: 2019-06-07
Authors: Irina A Kirpich; Craig J McClain; Vatsalya Vatsalya; Melanie Schwandt; Monte Phillips; Keith Cameron Falkner; Lucy Zhang; Catey Harwell; David T George; John C Umhau Journal: Alcohol Clin Exp Res Date: 2017-03-02 Impact factor: 3.455
Authors: Anna Warden; Emma Erickson; Gizelle Robinson; R Adron Harris; R Dayne Mayfield Journal: Pharmacogenomics Date: 2016-12-05 Impact factor: 2.533