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DOI: 10.1055/s-0037-1608832
Systematic Review and Meta-Analysis: Prevalence of Small Intestinal Bacterial Overgrowth in Chronic Liver Disease
Publication History
Publication Date:
22 December 2017 (online)
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Abstract
The authors conducted a meta-analysis of the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with chronic liver disease (CLD) and controls. Using the search terms “small intestinal bacterial overgrowth (SIBO)” and “chronic liver disease (CLD)” or “cirrhosis,” 19 case-control studies were identified. Utilizing breath tests, the prevalence of SIBO in CLD was 35.80% (95% CI, 32.60–39.10) compared with 8.0% (95% CI, 5.70–11.00) in controls. Using culture techniques, the prevalence was 68.31% (95% CI, 59.62–76.00) in CLD patients as compared with 7.94% (95% CI, 3.44–12.73) in controls. No difference between cirrhotic and noncirrhotic patients was found. SIBO is significantly more frequent in CLD patients as compared with controls. The association of SIBO and CLD was not confined to patients with advanced CLD, suggesting that SIBO is not a consequence of advanced liver disease but may play a role in the progression of CLD.
Funding
No external funding.
Author Contributions
Ayesha Shah and Gerald Holtmann—study idea, concept and design, data extraction and interpretation of data, drafting of the manuscript.
Graeme Macdonald—interpretation of data, drafting of the manuscript, review of final manuscript.
Linda Fletcher—interpretation of data, drafting of the manuscript, review of final manuscript.
Mark Morrison—drafting of the manuscript, review of final manuscript.
Mike Jones—data analysis, review of final manuscript.
Erin Shanahan—input into drafting of the manuscript, review of final manuscript.
Pegah Ghasemi—input into drafting of the manuscript, review of final manuscript.
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References
- 1 Resta SC. Effects of probiotics and commensals on intestinal epithelial physiology: implications for nutrient handling. J Physiol 2009; 587 (Pt 17): 4169-4174
- 2 Wu HJ, Wu E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes 2012; 3 (01) 4-14
- 3 Camilleri M, Madsen K, Spiller R, Greenwood-Van Meerveld B, Verne GN. Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterol Motil 2012; 24 (06) 503-512
- 4 Wiest R, Garcia-Tsao G. Bacterial translocation (BT) in cirrhosis. Hepatology 2005; 41 (03) 422-433
- 5 Deitch EA. Bacterial translocation of the gut flora. J Trauma 1990; 30 (12, Suppl) S184-S189
- 6 Berg RD. Bacterial translocation from the gastrointestinal tract. J Med 1992; 23 (3-4): 217-244
- 7 Guarner C, Soriano G. Bacterial translocation and its consequences in patients with cirrhosis. Eur J Gastroenterol Hepatol 2005; 17 (01) 27-31
- 8 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 (02) 302-309
- 9 American Gastroenterological Association medical position statement: guidelines for the evaluation and management of chronic diarrhea. Gastroenterology 1999; 116 (06) 1461-1463
- 10 Bouhnik Y, Alain S, Attar A. , et al. Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome. Am J Gastroenterol 1999; 94 (05) 1327-1331
- 11 Bardhan PK, Gyr K, Beglinger C, Vögtlin 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 (03) 253-256
- 12 Paik CN, Choi MG, Lim CH. , et al. The role of small intestinal bacterial overgrowth in postgastrectomy patients. Neurogastroenterol Motil 2011; 23 (05) e191-e196
- 13 Romagnuolo J, Schiller D, Bailey RJ. Using breath tests wisely in a gastroenterology practice: an evidence-based review of indications and pitfalls in interpretation. Am J Gastroenterol 2002; 97 (05) 1113-1126
- 14 Khoshini R, Dai SC, Lezcano S, Pimentel M. A systematic review of diagnostic tests for small intestinal bacterial overgrowth. Dig Dis Sci 2008; 53 (06) 1443-1454
- 15 Shanahan ER, Zhong L, Talley NJ, Morrison M, Holtmann G. Characterisation of the gastrointestinal mucosa-associated microbiota: a novel technique to prevent cross-contamination during endoscopic procedures. Aliment Pharmacol Ther 2016; 43 (11) 1186-1196
- 16 Bellot P, Francés R, Such J. Pathological bacterial translocation in cirrhosis: pathophysiology, diagnosis and clinical implications. Liver Int 2013; 33 (01) 31-39
- 17 Gäbele E, Dostert K, Hofmann C. , et al. DSS induced colitis increases portal LPS levels and enhances hepatic inflammation and fibrogenesis in experimental NASH. J Hepatol 2011; 55 (06) 1391-1399
- 18 Pijls KE, Jonkers DM, Elamin EE, Masclee AA, Koek GH. Intestinal epithelial barrier function in liver cirrhosis: an extensive review of the literature. Liver Int 2013; 33 (10) 1457-1469
- 19 Guarner C, Runyon BA, Young S, Heck M, Sheikh MY. Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites. J Hepatol 1997; 26 (06) 1372-1378
- 20 Llovet JM, Bartolí R, March F. , et al. Translocated intestinal bacteria cause spontaneous bacterial peritonitis in cirrhotic rats: molecular epidemiologic evidence. J Hepatol 1998; 28 (02) 307-313
- 21 Pande C, Kumar A, Sarin SK. Small-intestinal bacterial overgrowth in cirrhosis is related to the severity of liver disease. Aliment Pharmacol Ther 2009; 29 (12) 1273-1281
- 22 Leung C, Rivera L, Furness JB, Angus PW. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol 2016; 13 (07) 412-425
- 23 Stroup DF, Berlin JA, Morton SC. , et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283 (15) 2008-2012
- 24 Moher D, Liberati A, Tetzlaff J, Altman DG. ; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535
- 25 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315 (7109): 629-634
- 26 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21 (11) 1539-1558
- 27 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7 (03) 177-188
- 28 Miele L, Valenza V, La Torre G. , et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology 2009; 49 (06) 1877-1887
- 29 Martini GA, Phear EA, Ruebner B, Sherlock S. The bacterial content of the small intestine in normal and cirrhotic subjects: relation to methionine toxicity. Clin Sci 1957; 16 (01) 35-51
- 30 Gasbarrini A, Corazza GR, Gasbarrini G. , et al; 1st Rome H2-Breath Testing Consensus Conference Working Group. Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference. Aliment Pharmacol Ther 2009; 29 (Suppl. 01) 1-49
- 31 Bauer TM, Schwacha H, Steinbrückner B. , et al. Diagnosis of small intestinal bacterial overgrowth in patients with cirrhosis of the liver: poor performance of the glucose breath hydrogen test. J Hepatol 2000; 33 (03) 382-386
- 32 Zhong L, Shanahan ER, Raj A. , et al. Dyspepsia and the microbiome: time to focus on the small intestine. Gut 2017; 66 (06) 1168-1169
- 33 Steed H, Macfarlane GT, Blackett KL. , et al. Bacterial translocation in cirrhosis is not caused by an abnormal small bowel gut microbiota. FEMS Immunol Med Microbiol 2011; 63 (03) 346-354
- 34 Duseja A, Chawla YK. Obesity and NAFLD: the role of bacteria and microbiota. Clin Liver Dis 2014; 18 (01) 59-71
- 35 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 (02) 206-211
- 36 Abu-Shanab A, Quigley EM. The role of the gut microbiota in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2010; 7 (12) 691-701
- 37 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 (01) 213-221
- 38 Shanab AA, Scully P, Crosbie O. , et al. Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8. Dig Dis Sci 2011; 56 (05) 1524-1534
- 39 Quigley EMM. Microflora modulation of motility. J Neurogastroenterol Motil 2011; 17 (02) 140-147
- 40 Madrid AM, Hurtado C, Venegas M, Cumsille F, Defilippi C. Long-term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function. Am J Gastroenterol 2001; 96 (04) 1251-1255
- 41 Chesta J, Lillo R, Defilippi C. , et al. [Patients with liver cirrhosis: mouth-cecum transit time and gastric emptying of solid foods]. Rev Med Chil 1991; 119 (11) 1248-1253
- 42 Galati J, Holdeman K, Bottjen P. , et al. Delayed small-intestinal transit in chronic liver-disease. In: Gastroenterology. Philadelphia, PA: W. B. Saunders Co.; 1994: 19106-3399
- 43 Gunnarsdottir SA, Sadik R, Shev S. , et al. Small intestinal motility disturbances and bacterial overgrowth in patients with liver cirrhosis and portal hypertension. Am J Gastroenterol 2003; 98 (06) 1362-1370
- 44 Kwak DS, Jun DW, Seo JG. , et al. Short-term probiotic therapy alleviates small intestinal bacterial overgrowth, but does not improve intestinal permeability in chronic liver disease. Eur J Gastroenterol Hepatol 2014; 26 (12) 1353-1359
- 45 Chang CS, Chen GH, Lien HC, Yeh HZ. Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology 1998; 28 (05) 1187-1190
- 46 Bode C, Kolepke R, Schäfer K, Bode JC. Breath hydrogen excretion in patients with alcoholic liver disease--evidence of small intestinal bacterial overgrowth. Z Gastroenterol 1993; 31 (01) 3-7
- 47 Gupta A, Dhiman RK, Kumari S. , et al. Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy. J Hepatol 2010; 53 (05) 849-855
- 48 Sadik R, Abrahamsson H, Björnsson E, Gunnarsdottir A, Stotzer PO. Etiology of portal hypertension may influence gastrointestinal transit. Scand J Gastroenterol 2003; 38 (10) 1039-1044
- 49 Madrid AM, Cumsille F, Defilippi C. Altered small bowel motility in patients with liver cirrhosis depends on severity of liver disease. Dig Dis Sci 1997; 42 (04) 738-742
- 50 Stewart JJ, Battarbee HD, Farrar GE, Betzing KW. Intestinal myoelectrical activity and transit time in chronic portal hypertension. Am J Physiol 1992; 263 (4 Pt 1): G474-G479
- 51 Chesta J, Silva M, Thompson L, del Canto E, Defilippi C. [Bacterial overgrowth in small intestine in patients with liver cirrhosis]. Rev Med Chil 1991; 119 (06) 626-632
- 52 Morencos FC, de las Heras Castaño G, Martín Ramos L, López Arias MJ, Ledesma F, Pons Romero F. Small bowel bacterial overgrowth in patients with alcoholic cirrhosis. Dig Dis Sci 1995; 40 (06) 1252-1256
- 53 Yang CY, Chang CS, Chen GH. Small-intestinal bacterial overgrowth in patients with liver cirrhosis, diagnosed with glucose H2 or CH4 breath tests. Scand J Gastroenterol 1998; 33 (08) 867-871
- 54 Jun DW, Kim KT, Lee OY. , et al. Association between small intestinal bacterial overgrowth and peripheral bacterial DNA in cirrhotic patients. Dig Dis Sci 2010; 55 (05) 1465-1471
- 55 Madrid AM, Brahm J, Buckel E, Silva G, Defilippi C. Orthotopic liver transplantation improves small bowel motility disorders in cirrhotic patients. Am J Gastroenterol 1997; 92 (06) 1044-1045
- 56 Fleckenstein JF, Frank Sm, Thuluvath PJ. Presence of autonomic neuropathy is a poor prognostic indicator in patients with advanced liver disease. Hepatology 1996; 23 (03) 471-475
- 57 Thuluvath PJ, Triger DR. Autonomic neuropathy and chronic liver disease. Q J Med 1989; 72 (268) 737-747
- 58 Hendrickse MT, Triger DR. Peripheral and cardiovascular autonomic impairment in chronic liver disease: prevalence and relation to hepatic function. J Hepatol 1992; 16 (1-2): 177-183
- 59 Frith J, Newton JL. Autonomic dysfunction in chronic liver disease. Hepat Med 2011; 3: 81-87
- 60 Maheshwari A, Thuluvath PJ. Autonomic neuropathy may be associated with delayed orocaecal transit time in patients with cirrhosis. Auton Neurosci 2005; 118 (1-2): 135-139
- 61 Chang CS, Yang SS, Kao CH, Yeh HZ, Chen GH. Small intestinal bacterial overgrowth versus antimicrobial capacity in patients with spontaneous bacterial peritonitis. Scand J Gastroenterol 2001; 36 (01) 92-96
- 62 Bode JC, Bode C, Heidelbach R, Dürr HK, Martini GA. Jejunal microflora in patients with chronic alcohol abuse. Hepatogastroenterology 1984; 31 (01) 30-34
- 63 Bauer TM, Steinbrückner B, Brinkmann FE. , et al. Small intestinal bacterial overgrowth in patients with cirrhosis: prevalence and relation with spontaneous bacterial peritonitis. Am J Gastroenterol 2001; 96 (10) 2962-2967
- 64 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 2010; 55 (04) 1142-1148
- 65 Chander Roland B, Garcia-Tsao G, Ciarleglio MM, Deng Y, Sheth A. Decompensated cirrhotics have slower intestinal transit times as compared with compensated cirrhotics and healthy controls. J Clin Gastroenterol 2013; 47 (10) 888-893
- 66 Lombardo L, Foti M, Ruggia O, Chiecchio A. Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy. Clin Gastroenterol Hepatol 2010; 8 (06) 504-508
- 67 Law D, Pimentel M. Proton pump inhibitor therapy does not affect hydrogen production on lactulose breath test in subjects with IBS. Dig Dis Sci 2010; 55 (08) 2302-2308
- 68 Hutchinson S, Logan R. The effect of long-term omeprazole on the glucose-hydrogen breath test in elderly patients. Age Ageing 1997; 26 (02) 87-89
- 69 Thorens J, Froehlich F, Schwizer W. , et al. Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomised double blind study. Gut 1996; 39 (01) 54-59
- 70 Fried M, Siegrist H, Frei R. , et al. Duodenal bacterial overgrowth during treatment in outpatients with omeprazole. Gut 1994; 35 (01) 23-26
- 71 Chesta J, Defilippi C, Defilippi C. Abnormalities in proximal small bowel motility in patients with cirrhosis. Hepatology 1993; 17 (05) 828-832
- 72 Shindo K, Machida M, Miyakawa K, Fukumura M. A syndrome of cirrhosis, achlorhydria, small intestinal bacterial overgrowth, and fat malabsorption. Am J Gastroenterol 1993; 88 (12) 2084-2091
- 73 Sajjad A, Mottershead M, Syn WK, Jones R, Smith S, Nwokolo CU. Ciprofloxacin suppresses bacterial overgrowth, increases fasting insulin but does not correct low acylated ghrelin concentration in non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2005; 22 (04) 291-299
- 74 Qin N, Yang F, Li A. , et al. Alterations of the human gut microbiome in liver cirrhosis. Nature 2014; 513 (7516): 59-64
- 75 Carr RM, Oranu A, Khungar V. Nonalcoholic Fatty Liver Disease: Pathophysiology and Management. Gastroenterol Clin North Am 2016; 45 (04) 639-652
- 76 Sabaté JM, Jouët 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 (04) 371-377
- 77 Yao J, Chang L, Yuan L, Duan Z. Nutrition status and small intestinal bacterial overgrowth in patients with virus-related cirrhosis. Asia Pac J Clin Nutr 2016; 25 (02) 283-291