Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease
Abstract
Background/aims No information is yet available about the influence of alcohol abuse on the translocation of larger molecules (Mr>1200) through the intestinal mucosa in man. The present study aimed to determine the intestinal permeability to macromolecules in patients with chronic alcohol abuse and mild to more advanced stages of liver disease, and to measure the concentration of endotoxins in the plasma, as these compounds derive from the intestinal flora and are suspected to contribute to the development of alcoholic liver disease (ALD).Methods The permeability to polyethylene glycol Mr 400, Mr 1500, Mr 4000, and Mr 10,000 and endotoxin plasma concentrations were measured in 54 patients with alcoholic liver disease, 19 of them with cirrhosis, and in 30 non-alcoholic healthy controls.Results Permeability to polyethylene glycol Mr 400 was found to be unchanged in patients with ALD in comparison to healthy controls, whereas polyethylene glycol Mr 1500 and Mr 4000 were recovered in about twice as high concentrations in the urine of ALD patients (p<0.01). Polyethylene glycol Mr 10,000 was detected significantly less frequently in urine from healthy controls (0/30) than in urine of patients with alcoholic liver disease (20/54, p<0.01). Endotoxin concentrations in the plasma of alcoholics were increased more than 5-fold compared to healthy controls (p<0.01).Conclusions The results of this study indicate that alcohol abuse impairs the function of the intestinal barrier, which might enhance the translocation of bacterial toxins, thereby contributing to inflammatory processes in alcoholic liver disease.
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Increased blood lipopolysaccharide reflects gut leakiness and is accompanied by greater intestinal permeability to high molecular weight polyethylene glycol in alcoholic liver disease and to FITC-dextran in mouse models of alcoholic and biliary liver disease.
“Increases in blood LPS levels reflect gut leakiness and are mirrored by a number of other alterations such as increased intestinal permeability to high molecular weight polyethylene glycol in patients with ALD26 and to FITC-dextran in mouse models of alcoholic and biliary liver disease27,28.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [26]
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- Authors
- Parlesak, A., Schäfer, C., Schütz, T., Bode, J. C., & Bode, C.
- Affiliations
- University of Hohenheim (DE)
- Robert Bosch Hospital (DE)
- ORCID
- Parlesak, Alexandr
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2000-05
- Volume
- 32
- Issue
- 5
- Pages
- 742-747
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2017851289
- Cited by
- 647
- References
- 40
- Citations by year
- 2026: 14 · 2025: 25 · 2024: 35 · 2023: 30 · 2022: 37 · 2021: 49 · 2020: 37 · 2019: 34 · 2018: 35 · 2017: 45 · 2016: 32 · 2015: 52 · 2014: 29 · 2013: 26 · 2012: 29
- FWCI
- 6.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- intestinal permeability, macromolecules, endotoxemia, chronic alcohol abuse, alcoholic liver disease, alcoholic cirrhosis, intestinal barrier dysfunction, polyethylene glycol, bacterial translocation, endotoxin, gut microbiota
- MeSH terms
- Adult, Aged, Alcoholism, Cell Membrane Permeability, Endotoxins, Female, Humans, Intestinal Mucosa, Intestines, Liver Cirrhosis, Alcoholic, Male, Middle Aged, Polyethylene Glycols, Time Factors
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