Skip to main content
SpringerLink
Log in

Diminished Efficacy of Colonic Adaptation to Lactulose Occurs in Patients with Inflammatory Bowel Disease in Remission

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Lactulose has been proposed to be beneficial in treating inflammatory bowel disease (IBD). The hypothesis is based on the prebiotic potential of lactulose. A practical approach to testing its usefulness is to determine colonic adaptation to tolerable doses in patients with IBD. Our objective was to determine if a 3-week course of lactulose will decrease BH2 and symptoms in response to an acute lactulose challenge test in control subjects and IBD patients. The design was a Prospective cohort study. Subjects were given a 30-g lactulose challenge test (test 1), and then ingested 10 g of lactulose twice a day for 3 weeks before being retested (Test 2). A third test was given after a further 5-week washout period. The main outcomes were the change in 4-hr sum of BH2 (Σ4HrBH2) values obtained every 30 min, peak BH2, and 4-hr sum of symptom score (Σ4HrSS) during the lactulose challenge test. In addition, we also report the change in self-reported symptoms and diarrhea during the 3-week administration of lactulose. In controls, Σ4HrBH2 decreased from test 1 (380.5 ± 56.6 ppm) to test 2 (288.6 ± 57.4 ppm) (P < 0.05), and returned toward test 1 levels by test 3 (307.5 ± 53.1, P > 0.5). Unlike controls, the Σ4HrBH2 in patients failed to achieve significance between test 1 (444.5 ± 55.8 ppm), test 2 (366.5 ± 80.7 ppm, P > 0.2) or test 3 (411.6 ± 62.5 ppm, P > 0.2). Σ4HrSS results in controls followed a pattern similar to Σ4HrBH2, achieving significance only in test 2 (P < 0.02). Symptoms during the intertest periods decreased by the third week in controls (P < 0.05), but not in patients (P > 0.5). Symptoms were lower in patients and varied insignificantly both in challenges and intertest periods. In conclusion, although controls adapt to a 3-week period of lactulose ingestion, IBD patients fail to meet the criteria for adaptation. However, longer studies may be needed to establish whether IBD patients are slower to adapt.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Sartor RB: Current concepts of the etiology and pathogenesis of ulcerative colitis and Crohn's disease. Gastroenterol Clin North Am 24:475–507, 1995

    Google Scholar 

  2. Gorbach SL: Intestinal micro flora in inflammatory bowel disease—implications for etiology. In Inflammatory Bowel Disease. JB Kirsner, RG Shorter (eds). Philadelphia, Lea and Febiger, 1988, pp 51–64

    Google Scholar 

  3. Rutgeerts P, Goboes K, Peeters M, Hiele M, Penninckx F, Aerts R, Kerremans R, Vantrappen G: Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum. Lancet 338:771–774, 1991

    Google Scholar 

  4. Sutherland L, Singleton J, Sessions J, Hanauer S, Krawitt E, Rankin G, Summers R, Mekhjian H, Greenberger N, Kelly M: Double blind, placebo controlled trial of metronidazole in Crohn's disease. Gut 32:1071–1075, 1991

    Google Scholar 

  5. Peppercorn MA: Are antibiotics useful in the management of nontoxic severe ulcerative colitis? J Clin Gastroenterol 17:14–17, 1993

    Google Scholar 

  6. Elson CO, Sartor RB, Tennyson GS, Riddell RH: Experimental models of inflammatory bowel disease. Gastroenterology 109:1344–1367, 1995

    Google Scholar 

  7. Gionchetti P, Rizzello F, Venturi A, Brigidi P, Matteuzzi D, Bazzocchi G, Poggioli G, Miglioli M, Campieri M: Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119:305–309, 2000

    Google Scholar 

  8. Venturi A, Gionchetti P, Rizzello F, Johansson R, Zucconi E, Brigidi P, Matteuzzi D, Campieri M: Impact on the composition of the fecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis. Aliment Pharmacol Ther 13:1103–1108, 1999

    Google Scholar 

  9. Rembacken BJ, Snelling AM, Hawkey PM, Chalmers DM, Axon AT: Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 354:635–639, 1999

    Google Scholar 

  10. Kruis W, Schutz E, Fric P, Fixa B, Judmaier G, Stolte M: Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 11:853–858, 1997

    Google Scholar 

  11. Guslandi M, Mezzi G, Sorghi M, Testoni PA: Saccharomyces boulardii in maintenance treatment of Crohn's disease. Dig Dis sci 45:1462–1464, 2000

    Google Scholar 

  12. McCutcheon J, Fulton JD: Lowered prevalence of infection with lactulose therapy in patients in long-term hospital care. J Hosp Infect 13:81–86, 1989

    Google Scholar 

  13. Loguercio C, Abbiati R, Rinaldi M, Romano A, Del Vecchio B, Coltorti M: Long-term effects of Enterococcus faecium SF68 versus lactulose in the treatment of patients with cirrhosis and grade 1-2 hepatic encephalopathy. J Hepatol 23:39–46, 1995

    Google Scholar 

  14. Levine MM, Hornick RB: Lactulose therapy in Shigella carrier state and acute dysentery. Antimicrob Agents Chemother 8:581–584, 1975

    Google Scholar 

  15. Hansson HB, Barkenius G, Cronberg S, Juhlin I: Controlled comparison of nalidixic acid or lactulose with placebo in shigellosis. Scand J Infect Dis 13:191–193, 1981

    Google Scholar 

  16. Greve JW, Gouma DJ, von Leeuwen PA, Buurman WA: Lactulose inhibits endotoxin induced tumour necrosis factor production by monocytes. An in vitro study. Gut 31:198–203, 1990

    Google Scholar 

  17. Liao W, Cui XS, Jin XY, Floren CH: Lactulose—a potential drug for the treatment of inflammatory bowel disease. Med Hypotheses 43:234–238, 1994

    Google Scholar 

  18. Madsen KL, Doyle JS, Jewell LD, Tavernini MM, Fedorak RN: Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice. Gastroenterology 116:1107–1114, 1999

    Google Scholar 

  19. Florent C, Flourie B, Leblond A, Rautureau M, Bernier JJ, Rambaud JC: Influence of chronic lactulose ingestion on the colonic metabolism of lactulose in man (an in vivo study). J Clin Invest 75:608–613, 1985

    Google Scholar 

  20. Flourie B, Briet F, Florent C, Pellier P, Maurel M, Rambaud JC: Can diarrhea induced by lactulose be reduced by prolonged ingestion of lactulose? Am J Clin Nutr 58:369–375, 1993

    Google Scholar 

  21. Hertzler SR, Savaiano DA: Colonic adaptation to daily lactose feeding in lactose maldigesters reduces lactose intolerance. Am J Clin Nutr 64:232–236, 1996

    Google Scholar 

  22. Szilagyi A, Rivard J, Fokeeff K: Improved parameters of lactose maldigestion using lactulose. Dig Dis Sci 46:1509–1519, 2001

    Google Scholar 

  23. Hammer HF, Fine KD, Santa Ana CA, Porter JL, Schiller LR, Fordtran JS. Carbohydrate malabsorption: its measurement and its contribution to diarrhea. J Clin Invest 86:1936–1944, 1990

    Google Scholar 

  24. Metz G, Gassull MA, Leeds AR, Blendis LM, Jenkins DJ: A simple method of measuring breath hydrogen in carbohydrate malabsorption by end-expiratory sampling. Clin Sci Mol Med 50:237–240, 1976

    Google Scholar 

  25. van der Klei-van Moorsel JM, Douwes AC, van Oeveren JP: New principle for estimation of hydrogen in expired air. Eur J Pediatr 141:221–224, 1984

    Google Scholar 

  26. Barr RG, Watkins JB, Perman JA: Mucosal function and breath hydrogen excretion: comparative studies in the clinical evaluation of children with nonspecific abdominal complaints. Pediatrics 68:526–533, 1981

    Google Scholar 

  27. Kornbluth A, Sachar DB, Salomon P: Crohn's disease. In Sleisenger and Fordtran's Gastrointestinal and Liver Disease. Pathophysiology/Diagnosis/Management. M Feldman, BF Scharschmidt, MH Sleisenger (eds). Philadelphia, WB Saunders, 1998, pp 1708–1734

    Google Scholar 

  28. Jewel DP: Ulcerative colitis. In Sleisenger and Fordtran's Gastrointestinal and Liver Disease. Pathophysiology/Diagnosis/ Management. M Feldman, BF Scharschmidt, MH Sleisenger (eds). Philadelphia, WB Saunders, 1998, pp 1735–1761

    Google Scholar 

  29. Di Lorenzo C, Dooley CP, Valenzuela JE: Role of fasting gastrointestinal motility in the variability of gastrointestinal transit time assessed by hydrogen breath test. Gut 32:1127–1130, 1991

    Google Scholar 

  30. La Brooy SJ, Male PJ, Beavis AK, Misiewicz JJ: Assessment of the reproducibility of the lactulose H2 breath test as a measure of mouth to caecum transit time. Gut 24:893–896, 1983

    Google Scholar 

  31. Teuri U, Vapaatalo H, Korpela R: Fructooligosaccharides and lactulose cause more symptoms in lactose maldigesters and subjects with pseudohypolactasia than in control lactose digesters. Am J Clin Nutr 69:973–979, 1999

    Google Scholar 

  32. Briet F, Pochart P, Marteau P, Flourie B, Arrigoni E, Rambaud JC: Improved clinical tolerance to chronic lactose ingestion in subjects with lactose intolerance: a placebo effect. Gut 41:632–635, 1997

    Google Scholar 

  33. Stone-Dorshow T, Levitt MD: Gaseous response to ingestion of a poorly absorbed fructooligosaccharide sweetener. Am J Clin Nutr 46:61–65, 1987

    Google Scholar 

  34. Briet F, Achour L, Flourie B, Beaugerie L, Pellier P, Franchisseur C, Bornet F, Rambaud J-C: Symptomatic response to varying levels of fructo-oligosaccharides consumed occasionally or regularly. Euro J Clin Nutr 49:501–507, 1995

    Google Scholar 

  35. Van de Merwe JP, Schroder AM, Wensinck F, Hazenberg MP: The obligate anaerobic faecal flora of patients with Crohn's disease and their first-degree relatives. Scand J Gastroenterol 23:1125–1131, 1988

    Google Scholar 

  36. Hartley MG, Hudson MJ, Swarbride ET: The rectal mucosalassociated micro flora in patients with ulcerative colitis. J Med Microbiol 36:96–104, 1992

    Google Scholar 

  37. Favier C, Neut C, Mizon C, Cortot A, Colombel JF, Mizon J: Fecal beta-D-galactosidase production and Bifidobacteria are decreased in Crohn's disease. Dig Dis Sci 42:817–822, 1997

    Google Scholar 

  38. Tojo M, Oikawa T, Morikawa Y, Yamashita N, Iwata S, Satoh Y, Hanada J, Tanaka R: The effects of Bifidobacterium breve administration on Campylobacter enteritis. Acta Paediatr Jpn 29:160–167, 1987

    Google Scholar 

  39. Ortishi T, Sata M, Toyonaga A, Sasaki E, Tanikawa K: Evaluation of intestinal permeability in patients with inflammatory bowel disease using lactulose and measuring antibodies to lipid A. Gut 36:891–896, 1995

    Google Scholar 

  40. Soderholm JD, Peterson KH, Olaison G, Franzen LE, Westrom B, Magnusson KE, Sjodahl R: Epithelial permeability to proteins in the noninflamed ileum of Crohn's disease? Gastroenterology 117:65–72, 1999

    Google Scholar 

  41. Hollander D, Vadheim CM, Brettholz E, Petersen GM, Delahunty T, Rotter JI: Increased intestinal permeability in patients with Crohn's disease and their relatives. A possible etiologic factor. Ann Intern Med 105:883–885, 1986

    Google Scholar 

  42. Monajemi H, Meenan J, Lamping R, Obradov DO, Radema SA, Trown PW, Tytgat GN, Van Deventer SJ: Inflammatory bowel disease is associated with increased mucosal levels of bactericidal/permeability-increasing protein. Gastroenterology 110:733–739, 1996

    Google Scholar 

  43. Irvine EJ, Marshall JK: Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk. Gastroentreology 1999:1740–1744, 2000

    Google Scholar 

  44. Roberfroid MB: Prebiotics and probiotics: are they functional foods? Am J Clin Nutr 71:1682S-1687S, 2000

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada

    Andrew Szilagyi & Julie Rivard

  2. Centre for Clinical Epidemiology and Community Studies, Lady Davis Institute for Medical Research, McGill University, School of Medicine, Montreal, Quebec, Canada

    Julie Rivard & Ian Shrier

Authors
  1. Andrew Szilagyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Julie Rivard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ian Shrier
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Szilagyi, A., Rivard, J. & Shrier, I. Diminished Efficacy of Colonic Adaptation to Lactulose Occurs in Patients with Inflammatory Bowel Disease in Remission. Dig Dis Sci 47, 2811–2822 (2002). https://doi.org/10.1023/A:1021034028295

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1021034028295

Search

Navigation