Abnormal Intestinal Permeability in Primary Biliary Cirrhosis

Abstract

Antimitochondrial antibodies (AMAs) found in patients with primary biliary cirrhosis (PBC) cross-react with bacterial proteins and hence molecular mimicry has been proposed as a mechanism for AMA development. Alterations in gastrointestinal permeability would provide a potential route for increased exposure of gut flora to the immune system. In this study we aimed to compare the measured gastrointestinal permeability in patients with PBC to that in patients with liver disease (hepatitis C) and healthy control populations. Subjects drank a mixture of sucrose, lactulose, and mannitol dissolved in water. Eight-hour urinary excretion of the sugars was measured to assess intestinal permeability. Antiendomysial antibody testing was performed to exclude subclinical celiac disease. Eighty-six patients with PBC were evaluated and compared to 69 hepatitis C patients and 155 healthy controls. The mean urinary excretion of sucrose in the PBC patients (133.89 +/- 72.56 mg) was significantly higher than that in hepatitis C patients (101.07+/-63.35) or healthy controls (89.46+/-41.76) (P=0.0001), suggesting abnormal gastric or proximal small intestinal permeability. Sucrose excretion was not increased among patients with hepatitis C compared to healthy controls. The ratio of lactulose:mannitol excretion, reflecting small bowel permeability, was also elevated in the PBC group (0.017+/-0.012) compared to healthy controls (0.012+/-0.007) (P=0.0001) but was equal to that found among patients with hepatitis C (0.016+/-0.011) (P=NS). We conclude that the permeability of both the stomach and the small bowel is increased in patients with PBC, however, it is unclear if it is a cause, consequence, or manifestation of the disease.

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

“…These events lead to the generation of superoxide and the release of proinflammatory and profibrogenic cytokines such as TNF-␣, IL-1, IL-6, and IL-12, all of which induce liver damage (122,123). Consistent with these findings, microbial translocation has been shown to contribute to liver disease in several clinical settings, such as alcoholic liver disease (124,125) and other enteric processes (126)(127)(128). HIV coinfection with hepatitis viruses accelerates liver disease progression; however, the precise mechanisms by which this phenomenon occurs are not fully understood.…”

Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation?

“…The permeability of both the stomach and small intestine was increased in patients with PBC estimated by the sugar test and the L/M test [63]. The majority (66.6%) of patients with abnormal permeability did not have evidence of portal hypertension, and some patients with very early-stage PBC had increased permeability [63]. So far, no structural changes in the intestinal mucosa have been reported, although an IgA secretion defect in the intestinal epithelium was proposed [64].…”

The liver in celiac disease

“…These include increased intestinal permeability, which is an early abnormality in CD and has also been demonstrated in PBC. 41 Abnormal intestinal permeability can result in increased exposure of gut-derived antigens (including microbial antigens) to the immune system and specifically to the liver. 41,42 Additionally, there may be shared susceptibility (the development of two or more autoimmune diseases in one patient) to both PBC and CD through immunogenetic mechanisms.…”

“…41 Abnormal intestinal permeability can result in increased exposure of gut-derived antigens (including microbial antigens) to the immune system and specifically to the liver. 41,42 Additionally, there may be shared susceptibility (the development of two or more autoimmune diseases in one patient) to both PBC and CD through immunogenetic mechanisms. 43 The role of an immunological mechanism in PBC pathogenesis is supported by the fact that PBC is frequently (ϳ53% of cases) associated with autoimmune disorders, such as scleroderma, autoimmune thyroid disease, and keratoconjunctivitis sicca.…”