Academic journal article Alcohol Research: Current Reviews

The First Line of Defense: The Effects of Alcohol on Post-Burn Intestinal Barrier, Immune Cells, and Microbiome

Academic journal article Alcohol Research: Current Reviews

The First Line of Defense: The Effects of Alcohol on Post-Burn Intestinal Barrier, Immune Cells, and Microbiome

Article excerpt

Alcohol (ethanol) is one of the most globally abused substances, and is one of the leading causes of premature death in the world. As a result of its complexity and direct contact with ingested alcohol, the intestine represents the primary source from which alcohol-associated pathologies stem. The gut is the largest reservoir of bacteria in the body, and under healthy conditions, it maintains a barrier preventing bacteria from translocating out of the intestinal lumen. The intestinal barrier is compromised following alcohol exposure, which can lead to life-threatening systemic complications including sepsis and multiple organ failure. Furthermore, alcohol is a major confounding factor in pathology associated with trauma. Experimental data from both human and animal studies suggest that alcohol perturbs the intestinal barrier and its function, which is exacerbated by a "second hit" from traumatic injury. This article highlights the role of alcohol-mediated alterations of the intestinal epithelia and its defense against bacteria within the gut, and the impact of alcohol on intestinal immunity, specifically on T cells and neutrophils. Finally, it discusses how the gut microbiome both contributes to and protects the intestines from dysbiosis after alcohol exposure and trauma.

Key words: Alcohol use, abuse, and dependence; alcohol consumption; alcohol exposure; alcohol effects and consequences; burns; immunity; immune cells; microbiome; intestine; gut; intestinal lumen; intestinal barrier; bacteria; sepsis; organ failure; trauma; T cells; neutrophils; dysbiosis; human studies; animal models

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Each year 2.5 million people die from alcohol abuse and its related morbidities worldwide, making alcohol related deaths among the highest preventable causes of death, and the greatest cause of premature death and disability in men between ages 15 and 59 (World Health Organization 2011). Alcohol abuse predisposes individuals to life-threatening conditions such as alcoholic liver disease (ALD), acute respiratory distress syndrome (ARDS), sepsis, and multiple organ failure (MOF) (Bird and Kovacs 2008; Molina et al. 2003; Purohit et al. 2008). Further, studies show that intoxication often plays a role in physical injury (Pories et al. 1992). Data demonstrate that a majority of patients admitted to the hospital for traumatic injury have detectable blood alcohol levels at the time of admittance (Grobmyer et al. 1996; Jones et al. 1991; Maier 2001; McGill et al. 1995; McGwin et al. 2000; Silver et al. 2008). These patients generally require more extensive care than patients who have not been drinking. They more frequently require surgical intervention, experience higher susceptibility to infection, and have longer hospital stays (Silver et al. 2008). Supporting these observations, experimental data suggest that alcohol at the time of trauma results in more severe pathology in animal models (Choudhry and Chaudry 2008; Messingham et al. 2002; Molina et al. 2003, 2013). As a result, researchers estimate that in the United States alone, trauma and alcohol-related expenses to society total $185 billion annually (Li et al. 2004).

The disruptions to human biology that underlie the association between alcohol and these conditions bear exploring. The intestine, where alcohol first meets with digestive and immune mechanisms, is a primary source of alcohol-related pathologies. Here, alcohol and its metabolites encounter the physical barrier lining the gut that prevents invading pathogens from moving into the body. They also come into contact with a particularly complex frontier where the immune system must distinguish between commensal bacteria that normally colonize human intestines, and foreign microbes that cause disease. Any disruption of these systems by alcohol certainly could contribute to inflammatory states in the body that may in turn lead to serious conditions such as sepsis and MOF.

In support of these possibilities, data has shown that acute alcohol exposure negatively affects the function of the intestines, and this is exacerbated by a second traumatic insult such as burn injury (Akhtar et al. …

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