Role of inflammatory pathways, blood mononuclear cells, and gut-derived bacterial products in alcohol dependence

Sophie Leclercq, Christine De Saeger, Nathalie Delzenne, Philippe de Timary, Peter Stärkel
Biological Psychiatry 2014 November 1, 76 (9): 725-33

BACKGROUND: Inflammation might play a role in the development of several psychiatric diseases. However, the origins of processes that mediate inflammation are unknown. We previously reported increased intestinal permeability, elevated blood lipopolysaccharide levels, and low-grade systemic inflammation associated with psychological symptoms of alcohol dependence in alcohol-dependent subjects. In this study, we tested inflammatory responses of peripheral blood mononuclear cells (PBMCs) to gut-derived bacterial products during detoxification and the relationship to alcohol craving.

METHODS: In 63 actively drinking noncirrhotic alcohol-dependent subjects, testing was performed at the beginning (day 2) and end (day 18) of alcohol detoxification and compared with testing in 14 healthy subjects. Activation of various intracellular signaling pathways by gut-derived bacterial products was analyzed by quantitative polymerase chain reaction, Western blotting, and DNA binding assays (for transcription factors). Toll-like receptor activation was assessed by cell cultures.

RESULTS: In addition to lipopolysaccharides, we showed that peptidoglycans may also cross the gut barrier to reach the systemic circulation. Both activate their respective Toll-like receptors in peripheral blood mononuclear cells. Chronic alcohol consumption inhibited the nuclear factor kappa B proinflammatory cytokine pathway but activated the mitogen-activated protein kinase/activator protein 1 pathway, together with the inflammasome complex. This activity resulted in increased messenger RNA and plasma levels of interleukin (IL)-8, IL-1β, and IL-18. Activated proinflammatory pathways, in particular, IL-8 and IL-1β, were positively correlated with alcohol consumption and alcohol-craving scores. Short-term alcohol withdrawal was associated with the recovery of lipopolysaccharide-dependent receptors but not peptidoglycan-dependent receptors.

CONCLUSIONS: Lipopolysaccharides and peptidoglycans from the gut microbiota stimulate specific inflammatory pathways in peripheral blood mononuclear cells that are correlated with alcohol craving.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"