Potential Role of the Gut/Liver/Lung Axis in Alcohol-Induced Tissue Pathology

Abstract

Both Alcoholic Liver Disease (ALD) and alcohol-related susceptibility to acute lung injury are estimated to account for the highest morbidity and mortality related to chronic alcohol abuse and, thus, represent a focus of intense investigation. In general, alcohol-induced derangements to both organs are considered to be independent and are often evaluated separately. However, the liver and lung share many general responses to damage, and specific responses to alcohol exposure. For example, both organs possess resident macrophages that play key roles in mediating the immune/inflammatory response. Additionally, alcohol-induced damage to both organs appears to involve oxidative stress that favors tissue injury. Another mechanism that appears to be shared between the organs is that inflammatory injury to both organs is enhanced by alcohol exposure. Lastly, altered extracellular matrix (ECM) deposition appears to be a key step in disease progression in both organs. Indeed, recent studies suggest that early subtle changes in the ECM may predispose the target organ to an inflammatory insult. The purpose of this chapter is to review the parallel mechanisms of liver and lung injury in response to alcohol consumption. This chapter will also explore the potential that these mechanisms are interdependent, as part of a gut-liver-lung axis.

Modulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice

“…ALD is associated with changes in the intestinal microbiota composition in animal models and humans . Although taxonomic changes of the fecal‐ and mucosa‐associated microbiota have been characterized in patients with alcohol abuse, functional consequences are not well understood.…”

“…ALD is associated with changes in the intestinal microbiota composition in animal models and humans. (36,37) Although taxonomic changes of the fecal-and mucosa-associated microbiota have been characterized in patients with alcohol abuse, (5,6) functional consequences are not well understood. Using metagenomics and bile acid analysis, we demonstrate that chronic alcohol administration is associated with an increase in bacterial choloylglycine hydrolase, which deconjugates bile acids in the intestine of mice.…”

Risk factors profile for liver damage in cardiac inpatients

“…Unique characteristics of hospitalized cardiac patients (e.g. hypotension, hepatic ischemia, liver congestion, hepatotoxic cardiovascular drugs) probably potentiate well-known hepatotoxic action of alcohol even if it had been consumed in minute quantities before hospital admission [17][18][19] .…”

Transitional Remodeling of the Hepatic Extracellular Matrix in Alcohol-Induced Liver Injury

“…These changes to the ECM may not alter overall ECM architecture and are therefore histologically undetectable. Nevertheless, these changes have potential to alter hepatic phenotype and function (see Section 2) [73]. These acute responses can be viewed as an arm of the wound healing response and facilitate recovery from damage, which resolves once the damage is repaired.…”