Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity

Abstract

Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut-brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence.alcohol dependence | gut permeability | gut microbiota | gut-brain axis | behavior

The Microbiota, the Gut and the Brain in Eating and Alcohol Use Disorders: A ‘Ménage à Trois’?

“…This further suggests a role of the microbiomegut-brain axis in AUD. The low intestinal permeability group demonstrated reduced severity and duration of psychological symptoms, while the high intestinal permeability group showed persistent ADrelated behavioral changes throughout short-term abstinence, despite intestinal permeability recovery (Leclercq et al, 2014b). Two possible conclusions regarding the persistence of symptoms in the high intestinal permeability group were proposed (de Timary et al, 2015).…”

“…By checking auto-Ab levels and sequence homology comparisons between ED and healthy participants, the studies reviewed support the possibility that gut microbiota-driven dysregulation of neuroendocrine control of appetite leads to behavioral profiles associated with food intake in patients with EDs. With respect to AUD, chronic alcohol use induces dysbiosis and increased intestinal permeability in only a subset of alcohol dependent patients (Bode and Bode, 2003;Mutlu et al, 2012), allowing microbial metabolites to enter peripheral and central circulation and impact behavioral correlates such as alcohol craving (Leclercq et al, 2014b). Thus, chronic excessive alcohol use is necessary, but not sufficient to cause gut dysfunction in alcohol dependent patients (Mutlu et al, 2012;Leclercq et al, 2014b).…”

“…With respect to AUD, chronic alcohol use induces dysbiosis and increased intestinal permeability in only a subset of alcohol dependent patients (Bode and Bode, 2003;Mutlu et al, 2012), allowing microbial metabolites to enter peripheral and central circulation and impact behavioral correlates such as alcohol craving (Leclercq et al, 2014b). Thus, chronic excessive alcohol use is necessary, but not sufficient to cause gut dysfunction in alcohol dependent patients (Mutlu et al, 2012;Leclercq et al, 2014b). Still, gut microbial and peripheral metabolite level alterations were linked to alcohol craving, anxiety, and depression, which are important factors associated with relapse (de Timary et al, 2015).…”

MECHANISMS IN ENDOCRINOLOGY: Gut microbiota in patients with type 2 diabetes mellitus

“…Smoking cessation has also been suggested to influence the gut microbiota but other factors than smoking cessation per se, such as weight gain following smoking cessation, may confound this relationship (50). Recently, it has been shown that some alcohol-dependent subjects demonstrate increased intestinal permeability and alterations of the gut microbiota at the compositional and functional level, suggesting that alcohol may also play an important role (51).…”

A dysbiotic subpopulation of alcohol-dependent subjects

“…10,11 ) and the development of profound social impairment as observed in autistic spectrum disorders. [12][13][14] The paper we are commenting on here, 15 even though focusing on alcohol-dependence, also relates to depression and anxiety, as these Keywords: alcohol dependence, alcohol use disorders, behavior, depression, gut permeability, gut-brain axis, gut microbiota, leaky gut, negative reinforcement symptoms are an important dimension of alcohol-dependence. In the first part of the discussion, these aspects will be evoked at the light of the negative reinforcement process, that is a major dimension of the addictive process, 16 especially in chronic addiction.…”