Advertisement

Digestive Diseases and Sciences

, Volume 57, Issue 2, pp 545–553 | Cite as

Bifidobacterium longum with Fructo-Oligosaccharides in Patients with Non Alcoholic Steatohepatitis

  • Michele Malaguarnera
  • Marco Vacante
  • Tijana Antic
  • Maria Giordano
  • Giuseppe Chisari
  • Rosaria Acquaviva
  • Silvana Mastrojeni
  • Giulia Malaguarnera
  • Antonio Mistretta
  • Giovanni Li Volti
  • Fabio Galvano
Original Article

Abstract

Background

Increased exposure to intestinal bacterial products may contribute to the pathogenesis of non alcoholic steatohepatitis (NASH). Bifidobacteria are predominant bacterial species in the human gut microbiota and have been considered to exert a beneficial effect on human health by maintaining the equilibrium of the resident microbiota.

Aims

To evaluate the effects of Bifidobacterium longum with fructo-oligosaccharides (Fos) in the treatment of NASH.

Methods

A total of 66 patients were randomly and equally divided into two groups receiving Bifidobacterium longum with Fos and lifestyle modification (i.e., diet and exercise) versus lifestyle modification alone. The following variables were assessed at −4 (beginning of the dietary lead-in period), 0 (randomization), 6, 12, 18, and 24 weeks: aspartate transaminase (AST), alanine transaminase (ALT), bilirubin, albumin, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, fasting plasma glucose, insulin, C-peptide, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, homeostasis model assessment of insulin resistance (HOMA-IR), and serum endotoxins. Liver biopsies were performed at entry and repeated after 24 weeks of treatment.

Results

At the end of study period, we observed that the Bifidobacterium longum with Fos and lifestyle modification group versus the lifestyle modification alone group showed significant differences in the AST −69.6 versus −45.9 IU/mL (P < 0.05), LDL cholesterol −0.84 versus −0.18 mmol/L (P < 0.001), CRP −2.9 versus −0.7 mg/L (P < 0.05), TNF-α −0.45 versus −0.12 ng/mL (P < 0.001), HOMA-IR −1.1 versus −0.6 (P < 0.001), serum endotoxin −45.2 versus −30.6 pg/mL (P < 0.001), steatosis (P < 0.05), and the NASH activity index (P < 0.05).

Conclusions

Bifidobacterium longum with Fos and lifestyle modification, when compared to lifestyle modification alone, significantly reduces TNF-α, CRP, serum AST levels, HOMA-IR, serum endotoxin, steatosis, and the NASH activity index.

Keywords

Bifidobacterium longum Non alcoholic steatohepatitis Gut microbiota Steatosis TNF-α, probiotics 

Notes

Acknowledgments

This study was supported by a grant from the Regional Health Department for Sicily (Ric. Fin. 2007).

Conflict of interest

None of the authors had any relevant personal or financial conflicts of interest.

References

  1. 1.
    James O, Day C. Non-alcoholic steatohepatitis: another disease of affluence. Lancet. 1999;353:1634–1636.PubMedCrossRefGoogle Scholar
  2. 2.
    Pagano G, Pacini G, Musso G, et al. Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association. Hepatology. 2002;35:367–372.PubMedCrossRefGoogle Scholar
  3. 3.
    Hodge A, Hodge S, Chitturi S. Adipocytokine polymorphisms and nonalcoholic fatty liver disease. J Gastroenterol Hepatol. 2009;24:173–175.PubMedCrossRefGoogle Scholar
  4. 4.
    Marceau P, Biron S, Hould FS, Marceau S, Simard S, Thung SN, et al. Liver pathology and the metabolic syndrome X in severe obesity. J Clin Endocrinol Metab. 1999;84:1513–1517.PubMedCrossRefGoogle Scholar
  5. 5.
    Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology. 2010;52:79–104.PubMedCrossRefGoogle Scholar
  6. 6.
    Malaguarnera M, Gargante MP, Russo C, et al. L-carnitine supplementation to diet: a new tool in treatment of nonalcoholic steatohepatitis—a randomized and controlled clinical trial. Am J Gastroenterol. 2010;105:1338–1345.PubMedCrossRefGoogle Scholar
  7. 7.
    Nair S, Cope K, Risby TH, Diehl AM. Obesity and female gender increase breath ethanol concentration: potential implications for the pathogenesis of nonalcoholic steatohepatitis. Am J Gastroenterol. 2001;96:1200–1204.PubMedCrossRefGoogle Scholar
  8. 8.
    Yang SQ, Lin HZ, Lane MD, Clemens M, Diehl AM. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci USA. 1997;194:2557–2562.CrossRefGoogle Scholar
  9. 9.
    Haines NW, Baker AL, Boyer JL, et al. Prognostic indicators of hepatic injury following jejunoileal bypass performed for refractory obesity: a prospective study. Hepatology. 1981;1:161–167.PubMedCrossRefGoogle Scholar
  10. 10.
    Malaguarnera M, Greco F, Barone G, Gargante MP, Malaguarnera M, Toscano MA. Bifidobacterium longum with fructo-oligosaccharide (FOS) treatment in minimal hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. Dig Dis Sci. 2007;52:3259–3265.PubMedCrossRefGoogle Scholar
  11. 11.
    Malaguarnera M, Gargante MP, Malaguarnera G, et al. Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy. Eur J Gastroenterol Hepatol. 2010;22:199–206.PubMedCrossRefGoogle Scholar
  12. 12.
    Wigg AJ, Roberts-Thomson IC, Dymock RB, McCarthy PJ, Grose RH, Cummins AG. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis. Gut. 2001;48:206–211.PubMedCrossRefGoogle Scholar
  13. 13.
    Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology. 2004;39:1441–1449.PubMedCrossRefGoogle Scholar
  14. 14.
    Fuller R. Probiotics in human medicine. Gut. 1991;32:439–442.PubMedCrossRefGoogle Scholar
  15. 15.
    Macfarlane GT, Cummings JH. Probiotics and prebiotics: can regulating the activities of intestinal bacteria benefit health? West J Med. 1999;171:187–191.PubMedGoogle Scholar
  16. 16.
    Gibson GR, Beatty ER, Wang X, Cummings JH. Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. Gastroenterology. 1995;108:975–982.PubMedCrossRefGoogle Scholar
  17. 17.
    Daubioul CA, Taper HS, De Wispelaere LD, Delzenne NM. Dietary oligofructose lessens hepatic steatosis, but does not prevent hypertriglyceridemia in obese Zucker rats. J Nutr. 2000;130:1314–1319.PubMedGoogle Scholar
  18. 18.
    Wang X, Gibson GR. Effects of the in vitro fermentation of oligofructose and inulin by bacteria growing in the human large intestine. J Appl Bacteriol. 1993;75:373–380.PubMedCrossRefGoogle Scholar
  19. 19.
    Hidaka H, Hirayama M, Tokunaga T, Eida T. The effects of undigestible fructooligosaccharides on intestinal microflora and various physiological functions on human health. Adv Exp Med Biol. 1990;270:105–117.PubMedGoogle Scholar
  20. 20.
    Malaguarnera L, Cristaldi E, Malaguarnera M. The role of immunity in elderly cancer. Crit Rev Oncol Hematol. 2010;74:40–60.PubMedCrossRefGoogle Scholar
  21. 21.
    Malaguarnera L, Cristaldi E, Lipari H, Malaguarnera M. Acquired immunity: Immunosenescence and physical activity. Eur Rev Aging Phys Act. 2008;5:61–68.CrossRefGoogle Scholar
  22. 22.
    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486–2497.CrossRefGoogle Scholar
  23. 23.
    Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94:2467–2474.PubMedCrossRefGoogle Scholar
  24. 24.
    World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA. 1997;277:925–926.CrossRefGoogle Scholar
  25. 25.
    Ainsworth BE, Haskell WL, Leon AS, et al. Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc. 1993;25:71–80.PubMedCrossRefGoogle Scholar
  26. 26.
    Mathiesen UL, Franzén LE, Aselius H, et al. Increased liver echogenicity at ultrasound examination reflects degree of steatosis but not of fibrosis in asymptomatic patients with mild/moderate abnormalities of liver transaminases. Dig Liver Dis. 2002;34:516–522.PubMedCrossRefGoogle Scholar
  27. 27.
    Catalano D, Trovato GM, Martines GF, Randazzo M, Tonzuso A. Bright liver, body composition and insulin resistance changes with nutritional intervention: a follow-up study. Liver Int. 2008;28:1280–1287.PubMedCrossRefGoogle Scholar
  28. 28.
    Sanyal AJ. Treatment of non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2002;17:S385–S388.PubMedCrossRefGoogle Scholar
  29. 29.
    Kleiner DE, Brunt EM, Van Natta M, et al. Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–1321.PubMedCrossRefGoogle Scholar
  30. 30.
    Yang SQ, Lin HZ, Lane MD, Clemens M, Diehl AM. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci USA. 1997;94:2557–2562.PubMedCrossRefGoogle Scholar
  31. 31.
    Enomoto N, Ikejima K, Yamashina S, et al. Kupffer cell-derived prostaglandin E(2) is involved in alcohol-induced fat accumulation in rat liver. Am J Physiol Gastrointest Liver Physiol. 2000;279:G100–G106.PubMedGoogle Scholar
  32. 32.
    Yang SQ, Lin HZ, Mandal AK, Huang J, Diehl AM. Disrupted signaling and inhibited regeneration in obese mice with fatty livers: implications for nonalcoholic fatty liver disease pathophysiology. Hepatology. 2001;34:694–706.PubMedCrossRefGoogle Scholar
  33. 33.
    Solga SF, Diehl AM. Non-alcoholic fatty liver disease: lumen-liver interactions and possible role for probiotics. J Hepatol. 2003;38:681–687.PubMedCrossRefGoogle Scholar
  34. 34.
    Floch MH. Saccharomyces: is it a probiotic or a pathogen and what is the significance of an elevated anti-S. cerevisiae antibody? J Clin Gastroenterol. 2003;36:5–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Loguercio C, Federico A, Tuccillo C, et al. Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol. 2005;39:540–543.PubMedCrossRefGoogle Scholar
  36. 36.
    Daubioul CA, Horsmans Y, Lambert P, Danse E, Delzenne NM. Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: results of a pilot study. Eur J Clin Nutr. 2005;59:723–726.PubMedCrossRefGoogle Scholar
  37. 37.
    Thorburn A, Muir J, Proietto J. Carbohydrate fermentation decreases hepatic glucose output in healthy subjects. Metabolism. 1993;42:780–785.PubMedCrossRefGoogle Scholar
  38. 38.
    Englyst KN, Englyst HN, Hudson GJ, Cole TJ, Cummings JH. Rapidly available glucose in foods: an in vitro measurement that reflects the glycemic response. Am J Clin Nutr. 1999;69:448–454.PubMedGoogle Scholar
  39. 39.
    Luo J, Van Yperselle M, Rizkalla SW, Rossi F, Bornet FR, Slama G. Chronic consumption of short-chain fructooligosaccharides does not affect basal hepatic glucose production or insulin resistance in type 2 diabetics. J Nutr. 2000;130:1572–1577.PubMedGoogle Scholar
  40. 40.
    Li Z, Yang S, Lin H, et al. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology. 2003;37:343–350.PubMedCrossRefGoogle Scholar
  41. 41.
    Enomoto N, Takei Y, Yamashina S, Ikejima K, Kitamura T, Sato N. Anti-inflammatory strategies in alcoholic steatohepatitis. J Gastroenterol Hepatol. 2007;22:S59–S61.PubMedCrossRefGoogle Scholar
  42. 42.
    Malaguarnera L, Rosa MD, Zambito AM, dell’Ombra N, Marco RD, Malaguarnera M. Potential role of chitotriosidase gene in nonalcoholic fatty liver disease evolution. Am J Gastroenterol. 2006;101:2060–2069.PubMedCrossRefGoogle Scholar
  43. 43.
    Malaguarnera L, Di Rosa M, Zambito AM, dell’Ombra N, Nicoletti F, Malaguarnera M. Chitotriosidase gene expression in Kupffer cells from patients with non-alcoholic fatty liver disease. Gut. 2006;55:1313–1320.PubMedCrossRefGoogle Scholar
  44. 44.
    Malaguarnera M, Di Rosa M, Nicoletti F, Malaguarnera L. Molecular mechanisms involved in NAFLD progression. J Mol Med (Berl). 2009;87:679–695.CrossRefGoogle Scholar
  45. 45.
    Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA. 2001;285:2481–2485.PubMedCrossRefGoogle Scholar
  46. 46.
    Ridker PM, Morrow DA. C-reactive protein, inflammation, and coronary risk. Cardiol Clin. 2003;21:315–325.PubMedCrossRefGoogle Scholar
  47. 47.
    Abu-Shanab A, Quigley EM. The role of the gut microbiota in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2010;7:691–701.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Michele Malaguarnera
    • 3
  • Marco Vacante
    • 1
  • Tijana Antic
    • 1
  • Maria Giordano
    • 1
  • Giuseppe Chisari
    • 2
  • Rosaria Acquaviva
    • 3
  • Silvana Mastrojeni
    • 2
  • Giulia Malaguarnera
    • 2
  • Antonio Mistretta
    • 4
  • Giovanni Li Volti
    • 3
  • Fabio Galvano
    • 3
  1. 1.Department of Senescence, Urological and Neurological SciencesUniversity of CataniaCataniaItaly
  2. 2.Institute of MicrobiologyUniversity of CataniaCataniaItaly
  3. 3.Department of Biological Chemistry, Medical Chemistry and Molecular BiologyUniversity of CataniaCataniaItaly
  4. 4.Department of Hygiene and Public HealthUniversity of CataniaCataniaItaly

Personalised recommendations