Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease

Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: Summary of a symposium

“…An association between alcohol consumption and plasma endotoxin levels has been investigated in humans as well as in animals. Plasma endotoxin levels were significantly elevated in patients affected with different stages of ALD -fatty liver, hepatitis, and cirrhosis when compared with healthy control subjects (Fukui et al, 1991;Parlesak et al, 2000;Schafer et al, 2002). Amount of alcohol appeared to make significant impact on endotoxin levels and liver injury since in these studies healthy control subjects consumed less than 20 g/d of alcohol compared to more than 60 g/d of alcohol by ALD patients.…”

“…For example, an increased absorption of 51 Cr EDTA was found in subjects chronically abusing alcohol (Bjarnason et al, 1984) and an increase in absorption of polyethylene glycol (PEG) 400 was observed after the oral administration of alcohol to healthy volunteers (Robinson et al, 1981). To determine whether alcohol can increase intestinal permeability to macromolecules, permeability to PEG with different molecular masses (Mr 400, Mr 1500, Mr 4000, and Mr 10000) was measured in recently drinking alcoholics with different stages of ALD (Parlesak et al, 2000). The permeability to PEG Mr 400 was found to be unchanged when compared to healthy controls, whereas the permeability to PEG Mr 1500 and Mr 4000 were distinctly enhanced and the prevalence of increased permeability to PEG 10000 was more than 10-fold higher in alcoholics (Parlesak et al, 2000).…”

“…To determine whether alcohol can increase intestinal permeability to macromolecules, permeability to PEG with different molecular masses (Mr 400, Mr 1500, Mr 4000, and Mr 10000) was measured in recently drinking alcoholics with different stages of ALD (Parlesak et al, 2000). The permeability to PEG Mr 400 was found to be unchanged when compared to healthy controls, whereas the permeability to PEG Mr 1500 and Mr 4000 were distinctly enhanced and the prevalence of increased permeability to PEG 10000 was more than 10-fold higher in alcoholics (Parlesak et al, 2000). Direct evidence for increased gut permeability to endotoxin by alcohol was obtained in a rat study where intragastric administration of LPS (5 mg/kg) to alcohol-fed rats significantly increased portal vein endotoxin level after 2 hours (Mathurin et al, 2000).…”

Conjugated primary bile salts reduce permeability of endotoxin through intestinal epithelial cells and synergize with phosphatidylcholine in suppression of inflammatory cytokine production

“…This effect can be enhanced by prevention of intestinal overgrowth with Gram-negative bacteria (42). Hence, the supplementation of bile components seems useful also in other stages of clinical care that are prone to an elevated translocation of bacteria or endotoxins, namely, total parenteral nutrition (43), postoperative state of heart surgery (44), alcohol-induced liver disease (45), or endotoxemia itself (46).…”

“…Phosphatidylcholine was shown to be effective in the treatment of both ulcerative colitis (49) and alcohol-induced liver disease (50), the development of which has been associated with an increased intestinal permeability of endotoxins (45). However, this effect is mediated by direct phosphatidylcholine-leukocyte interaction, as evident from the experiments with leukocytes challenged directly with endotoxin in the presence of phosphatidylcholine.…”