Skip to main content

Advertisement

SpringerLink
Log in

Low-grade small intestinal bacterial overgrowth is common in patients with non-alcoholic steatohepatitis on quantitative jejunal aspirate culture

  • Original Article
  • Published:
Indian Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Though pathogenesis of non-alcoholic steatohepatitis (NASH) is unclear, association with small intestinal bacterial overgrowth [SIBO] and fecal dysbiosis is suggested. We evaluated SIBO in NASH using quantitative jejunal aspirate culture (conventional criteria: ≥ 105 colony forming unit (CFU)/mL and newer cutoff ≥ 103 CFU/mL) and glucose hydrogen breath test.

Methods

Thirty-eight patients with NASH (age 37.5 years, range 20–54, 9, 24% female), diagnosed by ultrasonography, alanine aminotransferase >1.5 times normal and liver biopsy (in 27/38, 71%) and exclusion of other causes and 12 constipation-predominant irritable bowel syndrome as historical controls (age 39.5-y, 26–44; 3, 25% female) without fatty liver were studied.

Results

Jejunal aspirates, obtained in 35/38 patients, were sterile in 14/35 (40%) and bacteria isolated in 21 (60%) (all aerobic, in one anaerobe also; Gram positive 5, negative 13, both 3). In contrast, bacteria (two Gram negative) were isolated in 3/12 (25%) controls (odds ratio 4.5, 95% CI 1.0–19.5; p = 0.04); colony counts were higher in NASH than controls (median 380 CFU/mL, 0–200,000 vs. 0 CFU/mL, 0–1000; p = 0.02). Gram negative bacteria tended to be commoner in NASH than controls (16/35 vs. 2/12; p = 0.07). Seven out of 35 (20%) patients with NASH (≥ 105 CFU/mL in 5 and 2 other on glucose hydrogen breath test) and no control had SIBO (p = ns); low-grade SIBO (≥103 CFU/mL) was commoner in NASH than controls (14/35, 40%, vs. 1/12, 8.3%; p = 0.04). There was no correlation between bacterial colony count and bacterial type and anthropometric and biochemical parameters.

Conclusion

Low-grade bacterial overgrowth, particularly with Gram negative bacteria, was commoner in NASH than controls.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bellentani S. The epidemiology of non-alcoholic fatty liver disease. Liver Int. 2017;37 Suppl 1:81–4.

  2. Agrawal S, Duseja AK. Non-alcoholic fatty liver disease: east versus west. J Clin Exp Hepatol. 2012;2:122–34.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999;30:1356–62.

    Article  CAS  PubMed  Google Scholar 

  4. Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149. 389-97:e10.

  5. Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, Benson JT, Enders FB, Angulo P. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut. 2009;58:1538–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ratziu V, Giral P, Charlotte F, et al. Liver fibrosis in overweight patients. Gastroenterology. 2000;118:1117–23.

    Article  CAS  PubMed  Google Scholar 

  7. Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology. 1990;12:1106–10.

    Article  CAS  PubMed  Google Scholar 

  8. Wiest R, Albillos A, Trauner M, Bajaj J, Jalan R. Targeting the gut-liver axis in liver disease. J Hepatol. 2017; pii: S0168-8278(17)32016-0.

  9. Sreenivasa Baba C, Alexander G, Kalyani B, et al. Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis. J Gastroenterol Hepatol. 2006;21:191–8.

    Article  PubMed  Google Scholar 

  10. Boursier J, Mueller O, Barret M, et al. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology. 2016;63:764–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Fialho A, Thota P, McCullough AJ, Shen B. Small intestinal bacterial overgrowth is associated with non-alcoholic fatty liver disease. J Gastrointestin Liver Dis. 2016;25:159–65.

    PubMed  Google Scholar 

  12. Kapil S, Duseja A, Sharma BK, et al. Small intestinal bacterial overgrowth and toll-like receptor signaling in patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2016;31:213–21.

    Article  CAS  PubMed  Google Scholar 

  13. 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;48:206–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sabate JM, Jouet P, Harnois F, et al. High prevalence of small intestinal bacterial overgrowth in patients with morbid obesity: a contributor to severe hepatic steatosis. Obes Surg. 2008;18:371–7.

    Article  PubMed  Google Scholar 

  15. Ghoshal UC, Ghoshal U. Small intestinal bacterial overgrowth and other intestinal disorders. Gastroenterol Clin N Am. 2017;46:103–20.

    Article  Google Scholar 

  16. Hocking MP, Duerson MC, O'Leary JP, Woodward ER. Jejunoileal bypass for morbid obesity. Late follow-up in 100 cases. N Engl J Med. 1983;308:995–9.

    Article  CAS  PubMed  Google Scholar 

  17. Li L, Liu DW, Yan HY, Wang ZY, Zhao SH, Wang B. Obesity is an independent risk factor for non-alcoholic fatty liver disease: evidence from a meta-analysis of 21 cohort studies. Obes Rev. 2016;17:510–9.

    Article  CAS  PubMed  Google Scholar 

  18. Drenick EJ, Fisler J, Johnson D. Hepatic steatosis after intestinal bypass--prevention and reversal by metronidazole, irrespective of protein-calorie malnutrition. Gastroenterology. 1982;82:535–48.

    CAS  PubMed  Google Scholar 

  19. Gangarapu V, Ince AT, Baysal B, et al. Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2015;27:840–5.

    Article  CAS  PubMed  Google Scholar 

  20. Ma YY, Li L, Yu CH, Shen Z, Chen LH, Li YM. Effects of probiotics on nonalcoholic fatty liver disease: a meta-analysis. World J Gastroenterol. 2013;19:6911–8.

  21. Duseja A, Chawla YK. Obesity and NAFLD: the role of bacteria and microbiota. Clin Liver Dis. 2014;18:59–71.

    Article  PubMed  Google Scholar 

  22. Ghoshal UC. How to interpret hydrogen breath tests. J Neurogastroenterol Motil. 2011;17:312–7.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ghoshal UC, Ghoshal U, Ayyagari A, et al. Tropical sprue is associated with contamination of small bowel with aerobic bacteria and reversible prolongation of orocecal transit time. J Gastroenterol Hepatol. 2003;18:540–7.

    Article  PubMed  Google Scholar 

  24. Misra A, Chowbey P, Makkar BM, et al. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India. 2009;57:163–70.

    CAS  PubMed  Google Scholar 

  25. Scatarige JC, Scott WW, Donovan PJ, Siegelman SS, Sanders RC. Fatty infiltration of the liver: ultrasonographic and computed tomographic correlation. J Ultrasound Med. 1984;3:9–14.

    Article  CAS  PubMed  Google Scholar 

  26. 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;94:2467–74.

    Article  CAS  PubMed  Google Scholar 

  27. Ghoshal U, Ghoshal UC, Ranjan P, Naik SR, Ayyagari A. Spectrum and antibiotic sensitivity of bacteria contaminating the upper gut in patients with malabsorption syndrome from the tropics. BMC Gastroenterol. 2003;3:9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Collee JG, Miles RS, Walt B. Tests for the identification of bacteria. In: Collee JG, Fraser AG, Marmion BP, Simmons A, editors. Mackie and McCartney Practical Medical Microbiology. New York: Churchill Livingstone; 1996. p. 131–49.

    Google Scholar 

  29. Anonymous. Processing clinical specimens for anaerobic bacteria: Isolation and identification procedures. In: Baron EJ, Peterson LR, Finegold SM, editors. Bailey and Scott’s Diagnostic Microbiology. Philadelphia: Mosby; 1994. p. 474–503.

    Google Scholar 

  30. Bardhan PK, Gyr K, Beglinger C, Vogtlin J, Frey R, Vischer W. Diagnosis of bacterial overgrowth after culturing proximal small-bowel aspirate obtained during routine upper gastrointestinal endoscopy. Scand J Gastroenterol. 1992;27:253–6.

    Article  CAS  PubMed  Google Scholar 

  31. Bala L, Ghoshal UC, Ghoshal U, et al. Malabsorption syndrome with and without small intestinal bacterial overgrowth: a study on upper-gut aspirate using 1H NMR spectroscopy. Magn Reson Med. 2006;56:738–44.

    Article  PubMed  Google Scholar 

  32. Lakshmi CP, Ghoshal UC, Kumar S, et al. Frequency and factors associated with small intestinal bacterial overgrowth in patients with cirrhosis of the liver and extra hepatic portal venous obstruction. Dig Dis Sci. 2009;55:1142–8.

    Article  PubMed  Google Scholar 

  33. Ghoshal UC, Srivastava D, Ghoshal U, Misra A. Breath tests in the diagnosis of small intestinal bacterial overgrowth in patients with irritable bowel syndrome in comparison with quantitative upper gut aspirate culture. Eur J Gastroenterol Hepatol. 2014;26:753–60.

    Article  CAS  PubMed  Google Scholar 

  34. Ghoshal UC, Srivastava D, Misra A, Ghoshal U. A proof-of-concept study showing antibiotics to be more effective in irritable bowel syndrome with than without small-intestinal bacterial overgrowth: a randomized, double-blind, placebo-controlled trial. Eur J Gastroenterol Hepatol. 2016;28:281–9.

    Article  CAS  PubMed  Google Scholar 

  35. Goel A, Gupta M, Aggarwal R. Gut microbiota and liver disease. J Gastroenterol Hepatol. 2014;29:1139–48.

    Article  PubMed  Google Scholar 

  36. Festi D, Schiumerini R, Eusebi LH, Marasco G, Taddia M, Colecchia A. Gut microbiota and metabolic syndrome. World J Gastroenterol. 2014;20:16079–94.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Greenhill C. Obesity: gut microbiota, host genetics and diet interact to affect the risk of developing obesity and the metabolic syndrome. Nat Rev Endocrinol. 2015;11:630.

    Article  CAS  PubMed  Google Scholar 

  38. Duseja A, Singh SP, Saraswat VA, et al. Non-alcoholic Fatty Liver Disease and Metabolic Syndrome-Position Paper of the Indian National Association for the Study of the Liver, Endocrine Society of India, Indian College of Cardiology and Indian Society of Gastroenterology. J Clin Exp Hepatol. 2015;5:51–68.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Riordan SM, McIver CJ, Williams R. Liver damage in human small intestinal bacterial overgrowth. Am J Gastroenterol. 1998;93:234–7.

    Article  CAS  PubMed  Google Scholar 

  40. Boursier J, Diehl AM. Implication of gut microbiota in nonalcoholic fatty liver disease. PLoS Pathog. 2015;11:e1004559.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Am J Gastroenterol. 2012;107:811–26.

    Article  PubMed  Google Scholar 

  42. Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology. 2014;146:1513–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Jiang W, Wu N, Wang X, et al. Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease. Sci Rep. 2015;5:8096.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wang B, Jiang X, Cao M, et al. Altered fecal microbiota correlates with liver biochemistry in nonobese patients with non-alcoholic fatty liver disease. Sci Rep. 2016;6:32002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Krajicek EJ, Hansel SL. Small intestinal bacterial overgrowth: A primary care review. Mayo Clin Proc. 2016;91:1828–33.

    Article  PubMed  Google Scholar 

  46. Corazza GR, Menozzi MG, Strocchi A, et al. The diagnosis of small bowel bacterial overgrowth. Reliability of jejunal culture and inadequacy of breath hydrogen testing. Gastroenterology. 1990;98:302–9.

    Article  CAS  PubMed  Google Scholar 

  47. Dellert SF, Nowicki MJ, Farrell MK, Delente J, Heubi JE. The 13C-xylose breath test for the diagnosis of small bowel bacterial overgrowth in children. J Pediatr Gastroenterol Nutr. 1997;25:153–8.

    Article  CAS  PubMed  Google Scholar 

  48. Ghoshal UC, Kumar S, Mehrotra M, Lakshmi C, Misra A. Frequency of small intestinal bacterial overgrowth in patients with irritable bowel syndrome and chronic non-specific diarrhea. J Neurogastroenterol Motil. 2010;16:40–6.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. Uday C Ghoshal and Chalamalasetty Sreenivasa Baba contributed equally to the work.

Authors and Affiliations

  1. Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India

    Uday C. Ghoshal, Chalamalasetty Sreenivasa Baba, George Alexander, Asha Misra, Vivek A Saraswat & Gourdas Choudhuri

  2. Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India

    Ujjala Ghoshal

Authors
  1. Uday C. Ghoshal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chalamalasetty Sreenivasa Baba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ujjala Ghoshal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. George Alexander
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Asha Misra
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vivek A Saraswat
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gourdas Choudhuri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Uday C. Ghoshal.

Ethics declarations

Conflict of interest

UCG, CSB, UG, GA, AM, VAS, and GC declare that they have no conflict of interest.

Ethics statement

The authors declare that the study was performed in a manner to conform with the Helsinki Declaration of 1975, as revised in 2000 and 2008, concerning Human and Animal Rights. The protocol was approved by the Institutional Ethics Committee and informed consent was obtained from the study subjects.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghoshal, U.C., Baba, C.S., Ghoshal, U. et al. Low-grade small intestinal bacterial overgrowth is common in patients with non-alcoholic steatohepatitis on quantitative jejunal aspirate culture. Indian J Gastroenterol 36, 390–399 (2017). https://doi.org/10.1007/s12664-017-0797-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12664-017-0797-6

Keywords

Search

Navigation