title: Role of intestinal permeability and inflammation in the biological and behavioral control of alcohol-dependent subjects.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Adult Psychiatry and Institute of Neurosciences, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Leclercq
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.forename: Audrey M
authors.initials: AM
authors.lastname: Neyrinck
authors.forename: Peter
authors.initials: P
authors.lastname: Stärkel
authors.forename: François
authors.initials: F
authors.lastname: Jamar
authors.forename: Moïra
authors.initials: M
authors.lastname: Mikolajczak
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Delzenne
authors.forename: Philippe
authors.initials: P
authors.lastname: de Timary
mesh_terms: D000437:Alcoholism / Q000473:pathology* / Q000523:psychology*; D001007:Anxiety / Q000523:psychology; D001288:Attention / Q000502:physiology; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D002860:Chromium Radioisotopes; D016207:Cytokines / Q000097:blood; D003863:Depression / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004492:Edetic Acid; D004751:Enteritis / Q000473:pathology* / Q000523:psychology*; D005260:Female; D006801:Humans; D007422:Intestines / Q000473:pathology* / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009770:Obsessive Behavior; D010539:Permeability; D011930:Reaction Time / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000523:psychology
chemical_list: D002860:Chromium Radioisotopes; D016207:Cytokines; D008070:Lipopolysaccharides; D002097:C-Reactive Protein; D004492:Edetic Acid