Bacterial translocation and changes in the intestinal microbiome associated with alcoholic liver disease

Abstract

Alcoholic liver disease progresses through several stages of tissue damage, from simple steatosis to alcoholic hepatitis, fibrosis, or cirrhosis. Alcohol also affects the intestine, increases intestinal permeability and changes the bacterial microflora. Liver disease severity correlates with levels of systemic bacterial products in patients, and experimental alcoholic liver disease is dependent on gut derived bacterial products in mice. Supporting evidence for the importance of bacterial translocation comes from animal studies demonstrating that intestinal decontamination is associated with decreased liver fibrogenesis. In addition, mice with a gene mutation or deletion encoding receptors for either bacterial products or signaling molecules downstream from these receptors, are resistant to alcohol-induced liver disease. Despite this strong association, the exact molecular mechanism of bacterial translocation and of how changes in the intestinal microbiome contribute to liver disease progression remains largely unknown. In this review we will summarize evidence for bacterial translocation and enteric microbial changes in response to alcoholic liver injury and chronic alcoholic liver disease. We will further describe consequences of intestinal dysbiosis on host biology. We finally discuss how therapeutic interventions may modify the gastrointestinal microflora and prevent or reduce alcoholic liver disease progression

Review article: alcohol and gut microbiota ‐ the possible role of gut microbiota modulation in the treatment of alcoholic liver disease

“…Since this microbe is able to degrade mucin, 21,22 some authors hypothesised that it could promote bacterial translocation (one of the factors involved in alcohol liver injury). 23 Moreover, Yan and colleagues in the same study showed that the population of Lactobacilli was depleted in alcohol-treated mice. 20 This last evidence could explain the beneficial effect of probiotics in the prevention of increased gut permeability, endotoxinemia and liver injury reported in alcoholfed mice.…”

“…Moreover the effects of probiotics are strain-dependent, therefore, further clinical studies are warranted to determine which probiotic strain should be used and which patient population should be treated. 23 Finally, further studies are warranted to assess the safety of administration of probiotics, in particular in patients with gut barrier leakage for the possible higher risk of systemic infection. 69,70 Another group of molecules able to modify gut microflora is represented by prebiotics.…”

“…20 Mechanisms of alcohol-induced changes on gut microbiota The reason for bacterial overgrowth and dysbiosis in alcoholic patients is not completely known. 23 Since alcohol can reduce gastrointestinal motility, this has been proposed as the key mechanism for faecal stasis and bacterial overgrowth, resulting in a higher number of luminal bacteria. 6,38 Alcohol-induced suppression of innate immune response (i.e.…”

Heart–Lung Interaction via Infection

“…Bacterial translocation from the GI tract to the peripheral circulation has been extensively studied in HIV infection, but is also common in liver disease and other conditions (24)(25)(26)(27). Translocation occurs early in HIV infection due to depletion of gut CD41 lymphocytes and is not completely eradicated by ART, particularly in patients with a suboptimal CD4 cell count or HIV viral level responses (25,28).…”

Alcohol and Obesity: A Dangerous Association for Fatty Liver Disease

“…These pathological alterations can directly or indirectly promote inflammation and fibrosis in fatty liver [50] . For instance, alcohol and obesity/diabetes lead to quantitative and qualitative changes of the microbiome and an impaired intestinal barrier, and these mechanisms are known to promote hepatic inflammation, fibrosis and cancerogenesis [51,52] . One further example is (visceral) adipose tissue, in which secretion of adipokines is altered by both obesity and alcohol.…”