Skip to main content
Top
Published in: Journal of Gastroenterology 3/2019

01-03-2019 | Original Article—Alimentary Tract

The role of small intestinal bacterial overgrowth in cystic fibrosis: a randomized case-controlled clinical trial with rifaximin

Authors: Manuele Furnari, Alessandra De Alessandri, Federico Cresta, Maria Haupt, Marta Bassi, Angela Calvi, Riccardo Haupt, Giorgia Bodini, Iftikhar Ahmed, Francesca Bagnasco, Edoardo Giovanni Giannini, Rosaria Casciaro

Published in: Journal of Gastroenterology | Issue 3/2019

Login to get access

Abstract

Background

Scientific literature shows a high prevalence of Small Intestinal Bacterial Overgrowth (SIBO) in patients with Cystic Fibrosis (CF). The role of SIBO in nutritional status and gastrointestinal symptoms in CF is not known. Our aim was to study epidemiology and clinical impact of SIBO while assessing the efficacy of rifaximin in eradicating SIBO in CF patients.

Methods

Symptoms questionnaire and Glucose Breath Test (GBT) were given to 79 CF patients (median age 19.6 years; 9.2–36.9). Subjects with a positive GBT were enrolled in a randomized controlled trial and received rifaximin 1200 mg for 14 days or no treatment. Questionnaire and GBT were repeated 1 month after the end of treatment or 45 days after the first negative GBT.

Results

Out of 79 patients, 25 were affected by SIBO (31.6%) with a significant correlation with lower BMI, SDS-BMI (p < 0.05) and serum albumin levels (p < 0.05), independently from pancreas insufficiency. Twenty-three patients took part in the randomized trial, 13 patients (56.5%) in rifaximin group and 10 patients (43.5%) in control group. Eradication rate of SIBO was 9/10 (90%) in rifaximin group and 2/6 (33.3%) in control group (p < 0.05). In the rifaximin group, gastrointestinal symptom improvement was observed in 4/5 patients aged ≤ 14 years and in 0/5 patients aged > 14 years (p < 0.05); in 2/6 patients in the control group.

Conclusions

CF patients show a high prevalence of SIBO, related to a poorer nutritional status. Rifaximin therapy is well tolerated and the results are promising in terms of efficacy in eradicating small intestinal bacterial overgrowth in CF.
Appendix
Available only for authorised users
Footnotes
1
The Study Protocol is available and can be requested at: Direzione Scientifica dell' Istituto G. Gaslini, Largo G Gaslini 5, 16147, Genoa, Italy. Mail: direzionescientifica@gaslini.org.
 
Literature
1.
go back to reference Strausbaugh SD, Davis PB. Cystic fibrosis: a review of epidemiology and pathobiology. Clin Chest Med. 2007;28:279–88.CrossRefPubMed Strausbaugh SD, Davis PB. Cystic fibrosis: a review of epidemiology and pathobiology. Clin Chest Med. 2007;28:279–88.CrossRefPubMed
2.
go back to reference Yen EH, Quinton MS, Borowitz D. Better nutritional status in early childhood is associated with improved clinical outcomes and survival in patients with cystic fibrosis. J Pediatr. 2013;162(530–535):e1. Yen EH, Quinton MS, Borowitz D. Better nutritional status in early childhood is associated with improved clinical outcomes and survival in patients with cystic fibrosis. J Pediatr. 2013;162(530–535):e1.
3.
go back to reference Grace E, Shaw C, Whelan K, et al. Review article: small intestinal bacterial overgrowth—prevalence, clinical features, current and developing diagnostic test, and treatment. Aliment Pharmacol Ther. 2013;38:674–88.CrossRefPubMed Grace E, Shaw C, Whelan K, et al. Review article: small intestinal bacterial overgrowth—prevalence, clinical features, current and developing diagnostic test, and treatment. Aliment Pharmacol Ther. 2013;38:674–88.CrossRefPubMed
4.
go back to reference Kerlin P, Wong L. Breath hydrogen testing in bacterial overgrowth of the small intestine. Gastroenterology. 1988;95:982–8.CrossRefPubMed Kerlin P, Wong L. Breath hydrogen testing in bacterial overgrowth of the small intestine. Gastroenterology. 1988;95:982–8.CrossRefPubMed
5.
go back to reference Shah SC, Day LW, Somsouk M, et al. Meta-analysis: antibiotic therapy for small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2013;38:925–34.CrossRefPubMed Shah SC, Day LW, Somsouk M, et al. Meta-analysis: antibiotic therapy for small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2013;38:925–34.CrossRefPubMed
6.
go back to reference Pimentel M. Review of rifaximin as treatment for SIBO and IBS. Expert Opin Investig Drugs. 2009;18:349–58.CrossRefPubMed Pimentel M. Review of rifaximin as treatment for SIBO and IBS. Expert Opin Investig Drugs. 2009;18:349–58.CrossRefPubMed
7.
go back to reference Furnari M, Parodi A, Gemignani E, et al. Clinical trial: the combination of rifaximin with partially hydrolysed guar gum is more effective than rifaximin alone in eradicating small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2010;32:1000–6.CrossRefPubMed Furnari M, Parodi A, Gemignani E, et al. Clinical trial: the combination of rifaximin with partially hydrolysed guar gum is more effective than rifaximin alone in eradicating small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2010;32:1000–6.CrossRefPubMed
8.
go back to reference Norkina O, Kaur S, Ziemer D, et al. Inflammation of the cystic fibrosis mouse small intestine. Am J Physiol Gastrointest Liver Physiol. 2004;286:G1032–41.CrossRefPubMed Norkina O, Kaur S, Ziemer D, et al. Inflammation of the cystic fibrosis mouse small intestine. Am J Physiol Gastrointest Liver Physiol. 2004;286:G1032–41.CrossRefPubMed
9.
go back to reference Clarke LL, Gaweins LR, Bradford EM, et al. Abnormal paneth cell granule dissolution and compromised resistance to bacterial colonization in the intestine of CF mice. Am J Physiol Gastrointest Liver Physiol. 2004;286:G1050–8.CrossRefPubMed Clarke LL, Gaweins LR, Bradford EM, et al. Abnormal paneth cell granule dissolution and compromised resistance to bacterial colonization in the intestine of CF mice. Am J Physiol Gastrointest Liver Physiol. 2004;286:G1050–8.CrossRefPubMed
10.
go back to reference Rovner AJ, Schall JI, Mondick JT, et al. Delayed small bowel transit in children with cystic fibrosis and pancreatic insufficiency. J Pediatr Gastroenterol Nutr. 2013;57:81–4.CrossRefPubMed Rovner AJ, Schall JI, Mondick JT, et al. Delayed small bowel transit in children with cystic fibrosis and pancreatic insufficiency. J Pediatr Gastroenterol Nutr. 2013;57:81–4.CrossRefPubMed
11.
go back to reference Borowitz D, Durie PR, Clarke LL. Gastrointestinal outcomes and confounders in cystic fibrosis. J Pediatr Gastroenterol Nutr. 2005;41:273–85.CrossRefPubMed Borowitz D, Durie PR, Clarke LL. Gastrointestinal outcomes and confounders in cystic fibrosis. J Pediatr Gastroenterol Nutr. 2005;41:273–85.CrossRefPubMed
12.
go back to reference Lewis SJ, Franco S, Young G, et al. Altered bowel function and duodenal bacterial overgrowth in patients treated with omeprazole. Aliment Pharmacol Ther. 1996;10:557–61.CrossRefPubMed Lewis SJ, Franco S, Young G, et al. Altered bowel function and duodenal bacterial overgrowth in patients treated with omeprazole. Aliment Pharmacol Ther. 1996;10:557–61.CrossRefPubMed
13.
go back to reference Weiss B, Bujanover Y, Yahav Y, et al. Probiotic supplementation affects pulmonary exacerbation in patients with cystic fibrosis: a pilot study. Pediatr Pulmonol. 2010;45:536–40.PubMed Weiss B, Bujanover Y, Yahav Y, et al. Probiotic supplementation affects pulmonary exacerbation in patients with cystic fibrosis: a pilot study. Pediatr Pulmonol. 2010;45:536–40.PubMed
14.
go back to reference Fridge JL, Conrad C, Gerson L, et al. Risk factors for small bowel bacterial overgrowth in cystic fibrosis. J Pediatr Gastroenterol Nutr. 2007;44:212–8.CrossRefPubMed Fridge JL, Conrad C, Gerson L, et al. Risk factors for small bowel bacterial overgrowth in cystic fibrosis. J Pediatr Gastroenterol Nutr. 2007;44:212–8.CrossRefPubMed
15.
go back to reference Lewindon PJ, Robb TA, Moore DJ, et al. Bowel dysfunction in cystic fibrosis: importance of breath testing. J Paediatr Child Health. 1998;34:79–82.CrossRefPubMed Lewindon PJ, Robb TA, Moore DJ, et al. Bowel dysfunction in cystic fibrosis: importance of breath testing. J Paediatr Child Health. 1998;34:79–82.CrossRefPubMed
16.
go back to reference Lisowska A, Wòjtowicz J, Walkowiak J. Small intestinal bacterial overgrowth is frequent in cystic fibrosis: combined hydrogen and methane measurements are required for its detection. Acta Biochim Pol. 2009;56:631–4.PubMed Lisowska A, Wòjtowicz J, Walkowiak J. Small intestinal bacterial overgrowth is frequent in cystic fibrosis: combined hydrogen and methane measurements are required for its detection. Acta Biochim Pol. 2009;56:631–4.PubMed
17.
go back to reference Farrell PM, Rosenstein BJ, White TB, et al. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report. J Pediatr. 2008;153:S4–14.CrossRefPubMedPubMedCentral Farrell PM, Rosenstein BJ, White TB, et al. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report. J Pediatr. 2008;153:S4–14.CrossRefPubMedPubMedCentral
18.
go back to reference Lisowska A, Pogorzelski A, Oracz G, et al. Oral antibiotic therapy improves fat absorption in cystic fibrosis patients with small intestine bacterial overgrowth. J Cystic Fibros. 2011;10:418–21.CrossRef Lisowska A, Pogorzelski A, Oracz G, et al. Oral antibiotic therapy improves fat absorption in cystic fibrosis patients with small intestine bacterial overgrowth. J Cystic Fibros. 2011;10:418–21.CrossRef
19.
go back to reference Saad RJ, Chey WD. Breath testing for small intestinal bacterial overgrowth: maximizing test accuracy. Clin Gastrenterol Hepatol. 2014;12:1964–72.CrossRef Saad RJ, Chey WD. Breath testing for small intestinal bacterial overgrowth: maximizing test accuracy. Clin Gastrenterol Hepatol. 2014;12:1964–72.CrossRef
20.
go back to reference Gemignani L, Savarino V, Ghio M, et al. Lactulose breath test to assess oro-cecal transit delay and estimate esophageal dysmotility in scleroderma patients. Semin Arthritis Rheum. 2013;42:522–9.CrossRefPubMed Gemignani L, Savarino V, Ghio M, et al. Lactulose breath test to assess oro-cecal transit delay and estimate esophageal dysmotility in scleroderma patients. Semin Arthritis Rheum. 2013;42:522–9.CrossRefPubMed
21.
go back to reference Beharry S, Ellis L, Corey M, et al. How useful is fecal pancreatic elastase 1 as a marker of exocrine pancreatic disease? J Pediatr. 2002;141:84–90.CrossRefPubMed Beharry S, Ellis L, Corey M, et al. How useful is fecal pancreatic elastase 1 as a marker of exocrine pancreatic disease? J Pediatr. 2002;141:84–90.CrossRefPubMed
22.
go back to reference Naruse S, Ishiguro H, Ko SBH, et al. Fecal pancreatic elastase: a reproducible marker for severe exocrine pancreatic insufficiency. J Gastroenterol. 2006;41:901–8.CrossRefPubMed Naruse S, Ishiguro H, Ko SBH, et al. Fecal pancreatic elastase: a reproducible marker for severe exocrine pancreatic insufficiency. J Gastroenterol. 2006;41:901–8.CrossRefPubMed
24.
go back to reference Karcher RE, Truding RM, Stawick LE. Using a cut off of < 10 ppm for breath hydrogen testing: a review of five years’ experience. Ann Clin Lab Sci. 1999;29:1–8.PubMed Karcher RE, Truding RM, Stawick LE. Using a cut off of < 10 ppm for breath hydrogen testing: a review of five years’ experience. Ann Clin Lab Sci. 1999;29:1–8.PubMed
26.
go back to reference Ghoshal UC, Ghoshal U, Das K, et al. Utility of hydrogen breath tests in diagnosis of small intestinal bacterial overgrowth in malabsorption syndrome and its relationship with oro-cecal transit time. Indian J Gastroenterol. 2006;25:6–10.PubMed Ghoshal UC, Ghoshal U, Das K, et al. Utility of hydrogen breath tests in diagnosis of small intestinal bacterial overgrowth in malabsorption syndrome and its relationship with oro-cecal transit time. Indian J Gastroenterol. 2006;25:6–10.PubMed
27.
go back to reference Drummey GD, Benson JA Jr, Jones CM. Microscopical examination of the stool for steatorrhea. N Engl J Med. 1961;264:85–7.CrossRefPubMed Drummey GD, Benson JA Jr, Jones CM. Microscopical examination of the stool for steatorrhea. N Engl J Med. 1961;264:85–7.CrossRefPubMed
29.
go back to reference Rolland-Cacherà MF, Cole TJ, Sempè M, et al. Body mass index variations: centiles from birth to 87 years. Eur J Clin Nutr. 1991;45:13–21.PubMed Rolland-Cacherà MF, Cole TJ, Sempè M, et al. Body mass index variations: centiles from birth to 87 years. Eur J Clin Nutr. 1991;45:13–21.PubMed
30.
go back to reference Bujanover Y, Peled Y, Blau H, et al. Methane production in patients with cystic fibrosis. Pediatr Gastroenterol Nutr. 1987;6:377–80.CrossRef Bujanover Y, Peled Y, Blau H, et al. Methane production in patients with cystic fibrosis. Pediatr Gastroenterol Nutr. 1987;6:377–80.CrossRef
31.
go back to reference Erdogan A, Rao SS, Gulley D, et al. Small intestinal bacterial overgrowth: duodenal aspiration vs glucose breath test. Neurogastroenterol Motil. 2015;27:481–9.CrossRefPubMed Erdogan A, Rao SS, Gulley D, et al. Small intestinal bacterial overgrowth: duodenal aspiration vs glucose breath test. Neurogastroenterol Motil. 2015;27:481–9.CrossRefPubMed
32.
go back to reference Yu D, Cheeseman F, Vanner S. Combined oro-cecal scintigraphy and lactulose hydrogen breath testing demonstrate that breath test is detects oro-cecal transit, not small intestinal bacterial overgrowth in patients with IBS. Gut. 2010;60:334–40.CrossRefPubMed Yu D, Cheeseman F, Vanner S. Combined oro-cecal scintigraphy and lactulose hydrogen breath testing demonstrate that breath test is detects oro-cecal transit, not small intestinal bacterial overgrowth in patients with IBS. Gut. 2010;60:334–40.CrossRefPubMed
33.
go back to reference Bratten JR, Spanier J, Jones MP. Lactulose breath testing does not discriminate patients with irritable bowel syndrome from healthy controls. Am J Gastroenterol. 2008;103:958–63.CrossRefPubMed Bratten JR, Spanier J, Jones MP. Lactulose breath testing does not discriminate patients with irritable bowel syndrome from healthy controls. Am J Gastroenterol. 2008;103:958–63.CrossRefPubMed
34.
go back to reference Walters B, Vanner SJ. Detection of bacterial overgrowth in IBS using lactulose H2 breath test: comparison with 14C-D-xylose and healthy controls. Am J Gastroenterol. 2005;100:1566–70.CrossRefPubMed Walters B, Vanner SJ. Detection of bacterial overgrowth in IBS using lactulose H2 breath test: comparison with 14C-D-xylose and healthy controls. Am J Gastroenterol. 2005;100:1566–70.CrossRefPubMed
35.
go back to reference Savarino E, Savarino V, Fox M, et al. Measurement of oro-caecal transit time by magnetic resonance imaging. Eur Radiol. 2015;25:1579–87.CrossRefPubMed Savarino E, Savarino V, Fox M, et al. Measurement of oro-caecal transit time by magnetic resonance imaging. Eur Radiol. 2015;25:1579–87.CrossRefPubMed
37.
go back to reference Lisowska A, Madry E, Pogorzelski A, et al. Small intestinal bacterial overgrowth does not correspond to intestinal inflammation in cystic fibrosis. Scand J Clin Lab Investig. 2010;70:322–6.CrossRef Lisowska A, Madry E, Pogorzelski A, et al. Small intestinal bacterial overgrowth does not correspond to intestinal inflammation in cystic fibrosis. Scand J Clin Lab Investig. 2010;70:322–6.CrossRef
38.
go back to reference Fundarò C, Fantacci C, Ansuini V, et al. Fecal calprotectin concentration in children affected by SIBO. Eur Rev Med Pharmacol Sci. 2011;15:1328–35.PubMed Fundarò C, Fantacci C, Ansuini V, et al. Fecal calprotectin concentration in children affected by SIBO. Eur Rev Med Pharmacol Sci. 2011;15:1328–35.PubMed
39.
go back to reference Stotzer PO, Blomberg L, Conway PL, et al. Probiotic treatment of small intestinal bacterial overgrowth by Lactobacillus fermentum. KLD Scand J infect Dis. 1996;28:615–9.CrossRefPubMed Stotzer PO, Blomberg L, Conway PL, et al. Probiotic treatment of small intestinal bacterial overgrowth by Lactobacillus fermentum. KLD Scand J infect Dis. 1996;28:615–9.CrossRefPubMed
40.
42.
go back to reference Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207–14.CrossRef Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207–14.CrossRef
43.
go back to reference Rodríguez JM, Murphy K, Stanton C, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26:26050.PubMed Rodríguez JM, Murphy K, Stanton C, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26:26050.PubMed
45.
go back to reference Jernberg C, Löfmark S, Edlund C, Jansson JK. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology. 2010;156:3216–23.CrossRefPubMed Jernberg C, Löfmark S, Edlund C, Jansson JK. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology. 2010;156:3216–23.CrossRefPubMed
46.
go back to reference Dethlefsen L, Huse S, Sogin ML, et al. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008;6:e280.CrossRefPubMedPubMedCentral Dethlefsen L, Huse S, Sogin ML, et al. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008;6:e280.CrossRefPubMedPubMedCentral
Metadata
Title
The role of small intestinal bacterial overgrowth in cystic fibrosis: a randomized case-controlled clinical trial with rifaximin
Authors
Manuele Furnari
Alessandra De Alessandri
Federico Cresta
Maria Haupt
Marta Bassi
Angela Calvi
Riccardo Haupt
Giorgia Bodini
Iftikhar Ahmed
Francesca Bagnasco
Edoardo Giovanni Giannini
Rosaria Casciaro
Publication date
01-03-2019
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 3/2019
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-018-1509-4

Other articles of this Issue 3/2019

Journal of Gastroenterology 3/2019 Go to the issue

Acknowledgment

Acknowledgements