Small Intestinal Bacterial Overgrowth-Diagnosis and Treatment

ig Dis 2007;25:237–240 D

DOI: 10.1159/0001032

mall Intestinal Bacterial Overgrowth: S

Diagnosis and Treatment

ntonio Gasbarrini Ernesto Cristiano Lauritano Maurizio Gabrielli A

Emidio Scarpellini Andrea Lupascu Veronica Ojetti Giovanni Gasbarrini

nternal Medicine Department, Gemelli Hospital, Catholic University of Sacred Heart, IRome , Italy ey Words K

Small intestinal bacterial overgrowth ؒ Antibiotics ؒ Breath

tests ؒ Irritable bowel syndrome

Introduction

Abstract

Small intestinal bacterial overgrowth (SIBO) is a clinical con-

dition characterized by a malabsorption syndrome due to an increase in microorganisms within the small intestine. The main mechanisms restricting bacterial colonization in the upper gut are the gastric acid barrier, mucosal and systemic immunity and intestinal clearance. When these mechanisms fail, bacterial overgrowth develops. Diarrhea, steatorrhea, chronic abdominal pain, bloating and flatulence are com-mon symptoms and are similar to those observed in irritable bowel syndrome. Breath tests (glucose and/or lactulose breath tests) have been proposed as a sensitive and simple tool for the diagnosis of bacterial overgrowth, being non-invasive and inexpensive compared to the gold standard represented by the culture of intestinal aspirates. Antibiotic therapy is the cornerstone of SIBO treatment. Current SIBO treatment is based on empirical courses of broad-spectrum antibiotics since few controlled studies concerning the choice and duration of antibiotic therapy are available at present. Copyright © 2007 S. Karger AG, Basel

dult humans live in symbiosis with several bacteria A

species exceeding the number of host somatic cells by at least one order of magnitude [1] . Intestinal microflora is a complex microbiological system composed of parasites, viruses, yeast and, above all, bacteria. The bacterial con-centration varies along the gastrointestinal tract increas-ing from 103 colony-forming units (CFU)/ml in the upper intestinal tract to 1014 CFU/ml in the colon.

Intestinal ecoflora is responsible for integrity and

function of the gastrointestinal tract. It plays a role in the defense from pathogenic microorganisms, in the stimu-lation of the immune system, in the control of metabolic and trophic function of epithelial cells and in the synthe-sis of vitamins and nutrients [2] . It also exerts remarkable effects in the development and maintenance of gut sen-sory and motor functions, including the promotion of intestinal propulsive activity.

There is emerging evidence indicating that quantita-

tive and qualitative changes in intestinal flora contribute to the pathogenesis of intestinal and extraintestinal dis-eases. Small intestinal bacterial overgrowth (SIBO) is a condition associated with the presence of 1 106 CFU/ml of intestinal aspirate and/or the presence of colonic-type species [3] . Normally, SIBO is prevented by action of the

Prof.AntonioGasbarrini

Internal Medicine Department, Catholic University of Sacred Heart

Gemelli Hospital, Largo A. Gemelli, 8 IT–00168 Rome (Italy)

Tel. +39 06 3015 4294, Fax +39 06 3550 2775, E-Mail angiologia@rm.unicatt.it

2007 S. Karger AG, Basel©

0257–2753/07/0253–0237$23.50/0 Accessibleonlineat:www.karger.com/ddi

intestinal immune system, gastric acid, pancreatic en- Diagnosis of Bacterial Overgrowth

zymes, small intestinal motility and the ileocecal valve. Aspiration and direct culture of jejunal contents are When one or more of these mechanisms fail, SIBO can

considered the gold standards for the diagnosis of SIBO occur.

[10] . These procedures have some limitations, such as in-vasivity, possible contamination by oropharyngeal bacte-Metabolic Effects of Bacterial Overgrowth ria, low reproducibility and presence of non-culturable

bacteria. For this reason, non-invasive tests are common-Bacteria in excess can interfere with the metabolism ly used for the diagnosis of SIBO (breath tests). These are

and the absorption of many substances such as carbohy-based on production of hydrogen and methane by bacte-drates, proteins, lipids and vitamins. The loss of activity ria as a consequence of carbohydrate fermentation [11] . of brush-border disaccharidases due to mucosal injury and the bacteria fermentation of sugars such as sorbitol, fructose and lactose could be responsible for carbohy-drate malabsorption [4] . Enterocyte injury may alter the gut permeability, predisposing to the development of a protein-losing enteropathy. Moreover, bacteria may com-pete with the host for protein and lead to the production of ammonia [5] . Deconjugation of bile acids in the proxi-mal gut induces fat and lipophilic vitamin (A, D, E) mal-absorption and leads to the production of lithocholic

acid, which is poorly absorbed and may be directly toxic

to enterocytes [6] . Cobalamin (vitamin B12 ) deficiency

can occur in SIBO as a result of use of the vitamin by an-aerobic bacteria. Levels of both folates and vitamin K, however, are usually normal or increased in SIBO as a result of bacterial production.

Clinical Aspects of Bacterial Overgrowth

S mall intestinal bacterial overgrowth is generally con-sidered a malabsorption syndrome, although clinical

manifestations can be largely different in each subject. This variability is caused by many factors including the entity of contamination, the extension of intestinal tract, the predisposing factors causing SIBO and the bacterial species involved. Common SIBO symptoms are diarrhea, steatorrhea, chronic abdominal pain, bloating and flatu-lence, although asymptomatic cases have been described [7] .

S

IBO symptoms are similar to those observed in pa-tients affected by irritable bowel syndrome (IBS). Recent findings suggest that SIBO could play a role in the patho-genesis and clinical manifestations of IBS and eradication of SIBO is associated with a significant improvement of

IBS symptoms [8,9]. H

owever, further studies are needed to confirm this clinical association. Unusual SIBO pre-sentations include megaloblastic anemia, osteomalacia, neuropathy, weight loss and peripheric edema.

238D

ig Dis 2007;25:237–240 The diagnosis of SIBO is established when the exhaled

hydrogen level increases by 1

1 0 parts per million greater than baseline (for glucose breath test) or when though double peaks (SIBO and colonic peaks) have been clearly found after lactulose ingestion. The specificity and sen-sitivity of breath tests are not excellent but they are a non-invasive, simple and inexpensive tool for the diagnosis of bacterial overgrowth. Treatment of Bacterial Overgrowth S IBO therapy is based on two different approaches: treatment of predisposing conditions and antibiotic ad-ministration. Little evidence exists for the efficacy of pro-kinetics and probiotics in SIBO treatment.A

ntibiotics A

lthough ideally the antibiotic choice should reflect in vitro susceptibility testing, this is usually difficult in SIBO because of the presence of several bacterial species with different antibiotic sensitivities. Therefore, antibi-otic treatment requires the administration of wide-spec-trum antibiotics, also if the best pharmacological ap-proach in terms of drug, dosage and duration of therapy remains to be assessed.

Tetracyclines have been used for a long time; however, this class of drugs is associated with several side effects and a low eradication rate (about 30%) since they do not have a direct activity against anaerobes and may be inef-fective against bacteroides [12] .

Metronidazole has been used with satisfying results as an alternative to tetracycline. In a study on patients with blind-loop syndrome, metronidazole showed a higher therapeutic efficacy than a non-absorbable antibiotic, ri-faximin [13] .

Gasbarrini/Lauritano/Gabrielli/

Scarpellini/Lupascu/Ojetti/Gasbarrini

Attaretal. [14] compare the efficacy of amoxicillin-clavulanic acid, norfloxacin, and Saccharomicesboular-dii for the treatment of SIBO-related diarrhea. A statisti-cally significant improvement in mean daily number of stools was obtained with norfloxacin (90%) and amoxi-cillin-clavulanic acid (60%), and none with S.boulardii. A study by Castiglione et al. [15] found a good therapeu-tic efficacy of both metronidazole and ciprofloxacin in terms of SIBO eradication in patients affected by Crohn’s disease. Ciprofloxacin showed a small, but not statisti-cally significant gain in terms of efficacy and tolerability compared to metronidazole. Some authors evaluated the therapeutic efficacy of non-absorbable antibiotics such as rifaximin and neomycin in order to minimize the poten-tial side effects of systemic antibiotics.

Data on rifaximin, a rifamycin derivative with anti- bacterial activity caused by inhibition of bacterial syn-thesis of RNA, show a bactericidal action against both aerobes and anaerobes, such as bacterioides, lactobacilli and clostridia [16] . Less than 0.1% of the oral dose of ri-faximin is absorbed, therefore it exhibits less toxicity than other antibiotics. In a double-blind controlled trial, Di Stefano et al. [12] compared the efficacy of rifaximin (1,200 mg/day) with respect to chlortetracycline in the short-term treatment of SIBO. The glucose breath test normalized in 70% of patients treated with rifaximin versus 27% of patients treated with chlortetracycline. No patient showed any side effect in the rifaximin group. Recently, Lauritano et al. [17] showed that higher doses of rifaximin (1,200 mg/day) were associated with a sig-nificantly higher therapeutic efficacy (60% of glucose breath test normalization) in terms of SIBO eradication with respect to doses of 600 mg/day (16.7% of glucose breath test normalization) and 800 mg/day (26.7% of glu-cose breath test normalization). Similarly, Cuoco et al. [18] assessed the efficacy of rifaximin (1,200 mg/day), followed by a 20-day course of probiotics, in the treat-ment of SIBO. The eradication rate of this schedule achieved 83% with a significant improvement of gastro-intestinal symptoms.Neomycin, a non-absorbable aminoglycoside, was

shown to be of little efficacy when used alone in SIBO. In a recent study by Pimentel et al. [19] on 111 IBS patients, treatment with neomycin achieved the normalization of lactulose breath test in 20% of patients with SIBO with respect to 2% in the placebo group. No relevant side ef-fects were observed during the study and no dropouts occurred. Given these data, there is no conclusive infor-mation regarding the most effective therapy that should be used in the treatment of SIBO. Treatment decisions should be individualized and consider risks of long-term antibiotic therapy (diarrhea, Clostridium difficile infec-tion, intolerance, bacterial resistance, costs) and the pos-sibility of SIBO recurrence.

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