Abstract
Background/objective:
Malnutrition is a prominent feature in liver cirrhosis, with deleterious impact on clinical outcome. The objective of this study is to investigate whether malnutrition is associated with increased gastrointestinal permeability in liver cirrhosis reflected by altered urinary excretion of non-metabolizable sugar probes.
Subjects/methods:
Patients with advanced liver cirrhosis (Child Pugh Score B or C) were recruited. Nutritional status was determined according to the Subjective Global Assessment. Intestinal permeability was assessed by measuring the urinary excretion of orally administered, non-metabolized sugar probe molecules. The lactulose/mannitol ratio served as marker for intestinal permeability and reflects non-carrier-mediated transcellular and paracellular transport of the small intestine during the first 5 h. Sucrose recovery in urine within the first 5 h reflects gastroduodenal permeability; sucralose recovery in urine 5–26 h after consumption reflects colonic permeability.
Results:
Sixty-four patients (56.7±10.8 years; 33% female) were included in the study. Twenty-one patients were considered well nourished according to the Subjective Global Assessment, 23 moderately nourished and 20 patients severely malnourished; 74% had alcoholic liver disease and 67% had cirrhosis stage Child C. Gastroduodenal and colonic permeability was significantly increased in patients with liver cirrhosis compared with 63 healthy controls (0.23±0.22 and 1.37±1.42% vs 0.14±0.10 and 0.41±0.72% in controls), but not different between well and malnourished subjects. Small intestinal permeability (lactulose/mannitol ratio) was increased in all patients (0.069±0.055%) and further increased in malnourished patients (0.048±0.031% vs 0.084±0.061%, P=0.004) due to decreased mannitol recovery only.
Conclusions:
Gastric, small intestinal and even colonic permeability was altogether increased in liver cirrhosis, and malnutrition was associated with further increased small intestinal permeability indicative of villous atrophy.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Alberino F, Gatta A, Amodio P, Merkel C, Di Pascoli L, Boffo G et al. Nutrition and survival in patients with liver cirrhosis. Nutrition 2001; 17: 445–450.
Muller MJ . Malnutrition in cirrhosis. J Hepatol 1995; 23: 31–35.
Selberg O, Selberg D . Norms and correlates of bioimpedance phase angle in healthy human subjects, hospitalized patients, and patients with liver cirrhosis. Eur J Appl Physiol 2002; 86: 509–516.
Selberg O, Bottcher J, Tusch G, Pichlmayr R, Henkel E, Muller MJ . Identification of high- and low-risk patients before liver transplantation: a prospective cohort study of nutritional and metabolic parameters in 150 patients. Hepatology 1997; 25: 652–657.
Zuckerman MJ, Menzies IS, Ho H, Gregory GG, Casner NA, Crane RS et al. Assessment of intestinal permeability and absorption in cirrhotic patients with ascites using combined sugar probes. Dig Dis Sci 2004; 49: 621–626.
Pascual S, Such J, Esteban A, Zapater P, Casellas JA, Aparicio JR et al. Intestinal permeability is increased in patients with advanced cirrhosis. Hepatogastroenterology 2003; 50: 1482–1486.
Keshavarzian A, Holmes EW, Patel M, Iber F, Fields JZ, Pethkar S . Leaky gut in alcoholic cirrhosis: a possible mechanism for alcohol-induced liver damage. Am J Gastroenterol 1999; 94: 200–207.
Pirlich M, Norman K, Lochs H, Bauditz J . Role of intestinal function in cachexia. Curr Opin Clin Nutr Metab Care 2006; 9: 603–606.
Bode C, Kugler V, Bode JC . Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess. J Hepatol 1987; 4: 8–14.
Norman K, Pirlich M . Gastrointestinal tract in liver disease: which organ is sick? Curr Opin Clin Nutr Metab Care 2008; 11: 613–619.
Reynolds JV, O’Farrelly C, Feighery C, Murchan P, Leonard N, Fulton G et al. Impaired gut barrier function in malnourished patients. Br J Surg 1996; 83: 1288–1291.
Bjarnason I, MacPherson A, Hollander D . Intestinal permeability: an overview. Gastroenterology 1995; 108: 1566–1581.
Meddings JB, Sutherland LR, Byles NI, Wallace JL . Sucrose: a novel permeability marker for gastroduodenal disease. Gastroenterology 1993; 104: 1619–1626.
Buhner S, Buning C, Genschel J, Kling K, Herrmann D, Dignass A et al. Genetic basis for increased intestinal permeability in families with Crohn’s disease: role of CARD15 3020insC mutation? Gut 2006; 55: 342–347.
Paganelli R, Fagiolo U, Cancian M, Scala E . Intestinal permeability in patients with chronic urticaria-angioedema with and without arthralgia. Ann Allergy 1991; 66: 181–184.
Detsky AS, McLaughlin JR, Baker JP, Johnston N, Whittaker S, Mendelson RA et al. What is subjective global assessment of nutritional status? J Parenter Enteral Nutr 1987; 11: 8–13.
Haas V, Buning C, Buhner S, von HC, Valentini L, Lochs H . Clinical relevance of measuring colonic permeability. Eur J Clin Invest 2009; 39: 139–144.
Bijlsma PB, Peeters RA, Groot JA, Dekker PR, Taminiau JA, Van Der Meer R . Differential in vivo and in vitro intestinal permeability to lactulose and mannitol in animals and humans: a hypothesis. Gastroenterology 1995; 108: 687–696.
Cobden I, Dickinson RJ, Rothwell J, Axon AT . Intestinal permeability assessed by excretion ratios of two molecules: results in coeliac disease. Br Med J 1978; 2: 1060.
Juby LD, Rothwell J, Axon AT . Cellobiose/mannitol sugar test--a sensitive tubeless test for coeliac disease: results on 1010 unselected patients. Gut 1989; 30: 476–480.
Menzies IS, Laker MF, Pounder R, Bull J, Heyer S, Wheeler PG et al. Abnormal intestinal permeability to sugars in villous atrophy. Lancet 1979; 2: 1107–1109.
Nathavitharana KA, Lloyd DR, Raafat F, Brown GA, McNeish AS . Urinary mannitol: lactulose excretion ratios and jejunal mucosal structure. Arch Dis Child 1988; 63: 1054–1059.
Ukabam SO, Cooper BT . Small intestinal permeability to mannitol, lactulose, and polyethylene glycol 400 in celiac disease. Dig Dis Sci 1984; 29: 809–816.
Bode JC, Knuppel H, Schwerk W, Lorenz-Meyer H, Durr HK . Quantitative histomorphometric study of the jejunal mucosa in chronic alcoholics. Digestion 1982; 23: 265–270.
Persson J, Berg NO, Sjolund K, Stenling R, Magnusson PH . Morphologic changes in the small intestine after chronic alcohol consumption. Scand J Gastroenterol 1990; 25: 173–184.
Seitz HK, Velasquez D, Waldherr R, Veith S, Czygan P, Weber E et al. Duodenal gamma-glutamyltransferase activity in human biopsies: effect of chronic ethanol consumption and duodenal morphology. Eur J Clin Invest 1985; 15: 192–196.
De Palma GD, Rega M, Masone S, Persico F, Siciliano S, Patrone F et al. Mucosal abnormalities of the small bowel in patients with cirrhosis and portal hypertension: a capsule endoscopy study. Gastrointest Endosc 2005; 62: 529–534.
Elia M, Goren A, Behrens R, Barber RW, Neale G . Effect of total starvation and very low calorie diets on intestinal permeability in man. Clin Sci (Lond) 1987; 73: 205–210.
Marchesini G, Bianchi G, Lucidi P, Villanova N, Zoli M, De FP . Plasma ghrelin concentrations, food intake, and anorexia in liver failure. J Clin Endocrinol Metab 2004; 89: 2136–2141.
Norman K, Smoliner C, Stobaeus N, Schutz T, Lochs H, Ockenga J et al. T1475 early enteral nutrition improves functional parameters in liver cirrhosis. Gastroenterology 2008; 134: A563–A564.
Izbeki F, Kiss I, Wittmann T, Varkonyi TT, Legrady P, Lonovics J . Impaired accommodation of proximal stomach in patients with alcoholic liver cirrhosis. Scand J Gastroenterol 2002; 37: 1403–1410.
Aqel BA, Scolapio JS, Dickson RC, Burton DD, Bouras EP . Contribution of ascites to impaired gastric function and nutritional intake in patients with cirrhosis and ascites. Clin Gastroenterol Hepatol 2005; 3: 1095–1100.
Aprile LR, Meneghelli UG, Martinelli AL, Monteiro CR . Gastric motility in patients with presinusoidal portal hypertension. Am J Gastroenterol 2002; 97: 3038–3044.
Kalaitzakis E, Simren M, Abrahamsson H, Bjornsson E . Role of gastric sensorimotor dysfunction in gastrointestinal symptoms and energy intake in liver cirrhosis. Scand J Gastroenterol 2007; 42: 237–246.
Monteleone P, Carratu R, Carteni M, Generoso M, Lamberti M, Magistris LD et al. Intestinal permeability is decreased in anorexia nervosa. Mol Psychiatry 2004; 9: 76–80.
Welsh FK, Farmery SM, MacLennan K, Sheridan MB, Barclay GR, Guillou PJ et al. Gut barrier function in malnourished patients. Gut 1998; 42: 396–401.
Acknowledgements
We thank Martina Werich for technical assistance.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
Contributors: KN and SB conceived the study and performed the analysis; KN, MP and CS recruited the patients; KN, MP and SB wrote the manuscript; JS, LV and HL contributed significant advice.
Rights and permissions
About this article
Cite this article
Norman, K., Pirlich, M., Schulzke, JD. et al. Increased intestinal permeability in malnourished patients with liver cirrhosis. Eur J Clin Nutr 66, 1116–1119 (2012). https://doi.org/10.1038/ejcn.2012.104
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ejcn.2012.104
Keywords
This article is cited by
-
Alteration in the mRNA expression of genes associated with gastrointestinal permeability and ileal TNF-α secretion due to the exposure of silver nanoparticles in Sprague–Dawley rats
Journal of Nanobiotechnology (2019)
-
Impact of Laparoscopic Sleeve Gastrectomy on Gut Permeability in Morbidly Obese Subjects
Obesity Surgery (2019)
-
Effect of caloric restriction on gut permeability, inflammation markers, and fecal microbiota in obese women
Scientific Reports (2017)
-
Serum interleukin 8 and 12 levels predict severity and mortality in patients with alcoholic hepatitis
Indian Journal of Gastroenterology (2015)
-
Intestinal permeability – a new target for disease prevention and therapy
BMC Gastroenterology (2014)