In contrast to the large intestine, the concentration of the bacteria in the small intestine rarely exceeds 1,000 organisms/mL. Gastric acid secretion and intestinal motility limit the overgrowth of bacteria in the small intestine. When these protective mechanisms against excessive bacterial growth fail, small intestinal bacterial overgrowth (SIBO) can manifest. SIBO refers to a condition in which excess bacteria in the small intestine produces intestinal symptoms. Due to its increased awareness and understanding, SIBO is now often considered in most clinician’s differential diagnosis in patients with non-specific gastrointestinal complaints.
The etiology of small intestinal bacterial overgrowth is complex. There are many important host defense mechanisms against bacterial overgrowth. When these protective barriers fail, SIBO occurs. Upon ingestion of food, gastric acids and bile destroy and prevent bacteria from passing through the intestines. Conditions that cause achlorhydria are associated with SIBO. Also, proteolytic enzymes digest and degrade bacteria in the intestines. Chronic pancreatic insufficiency is associated with SIBO. Migrating motor complex is responsible for peristalsis and cleansing the small intestine. SIBO is associated with disorders of abnormal gastrointestinal motility, such as irritable bowel syndrome, narcotic use, post-radiation enteropathy, hypothyroidism, diabetes mellitus, and scleroderma.
An intact ileocecal valve and antegrade motility prevent retrograde translocation of colonic bacteria. Anatomic abnormalities lead to stasis of the bowels which may predispose to SIBO. Such anatomic disorders may include small intestinal diverticulosis, bowel strictures, post-operative adhesions, gastric bypasses with blind intestinal loops and ileocecal resection. Lastly, immunoglobin A, which found in abundance in the gastrointestinal tract, also prevents bacterial proliferation and maintains intestinal immunity. Immunodeficiency disorders, such as acquired immune deficiency syndrome, combined variable immunodeficiency, and IgA deficiency, are associated with increased risk of SIBO.
The actual prevalence of small intestinal bacterial overgrowth is vastly unknown. Disorders of abnormal gastrointestinal motility account for the majority of the cases.
Research has identified multiple species in SIBO. The most common species include Streptococcus, Escherichia coli, Lactobacillus and Bacteroides. The presence of overabundant bacteria in the small intestines does not always correlate with disease activity. Clinical manifestations only occur when inflammation from invasive strains of bacteria are present. Invasive strains of bacteria can produce enzymes or endotoxins, which damages the epithelial cell layer.
In SIBO, the endoscopic and histopathological appearance of the mucosa is usually healthy. Nonspecific endoscopic changes may include mucosal edema, loss of vascularity, patchy erythema, or rarely ulceration. Nonspecific histopathological findings may consist of villous blunting, cryptitis, intraepithelial lymphocytosis, and eosinophilia.
The clinical manifestations of small intestinal bacterial overgrowth classically include a combination of abdominal discomfort with bloating, flatulence, or chronic watery diarrhea. Steatorrhea and weight loss from fat malabsorption may manifest as well. SIBO causes vitamin deficiencies. Vitamin B12 deficiency occurs from ileal mucosal damage to cobalamin binding sites. Vitamin B1 and B3 deficiencies occur due to bacterial overutilization. In contrast, bacterial synthesis results in the elevation of folate and vitamin K levels.
D-lactic acidosis, a rare neurological syndrome, is characterized by altered mental status, slurred speech, seizures, and ataxia. This syndrome results from bacterial fermentation of unabsorbed carbohydrates. Patients with SIBO associated with short bowel syndrome or a jejunoileal bypass can develop this syndrome. SIBO has been implicated in the development of nonalcoholic fatty liver disease and hepatic encephalopathy. Unless severe malnutrition is evident, physical examination in these patients is generally nonrevealing.
There is no validated gold standard diagnostic test for small intestinal bacterial overgrowth. When a patient is presenting with signs and symptoms concerning of SIBO, the diagnosis garners further support with a positive carbohydrate breath test or a bacterial concentration of more than 1000 colony-forming units/mL in a jejunal aspirate culture. A carbohydrate breath test is a noninvasive, fast, and inexpensive test. The test uses the principle that the metabolism of either lactulose or glucose as its carbohydrate substrate by bacteria will produce either hydrogen or methane. This product will then be absorbed and excreted in the patient’s breath. A rise of more than 20 parts per million from baseline in hydrogen within 90 minutes or a methane level of more than 10 parts per million are positive results.
A jejunal aspirate culture is invasive, time-consuming, and expensive, as it is obtained during an upper endoscopy. The results are also poorly reproducible and can lead to false results from either patchy bacterial overgrowth or contamination with oropharyngeal flora. Other laboratory findings that support a diagnosis of SIBO may include vitamin levels and markers of malnutrition. Once there is a suspicion of SIBO, additional testing in identifying the etiology merit consideration. Anatomic and mucosal abnormalities can be investigated with abdominal imaging and endoscopies. Testing for disorders of abnormal gastrointestinal motility, pancreatic insufficiency, and immunodeficiencies can be considerations on a case-by-case basis.
The initial mainstay of treatment is the use of antibiotics to eradicate bacterial overgrowth and repletion of any nutritional deficiencies. Metronidazole, ciprofloxacin, tetracycline, amoxicillin-clavulanate, neomycin, and rifaximin are antibiotics used in the treatment, with rifaximin being the most investigated. For patients with hydrogen-predominant bacterial overgrowth, rifaximin 1650 mg/day for two weeks is an effective therapy. For patients with methane-predominant bacterial overgrowth, the combination of neomycin 1000 mg/day and rifaximin 1650 mg/day for two weeks is an effective therapy.
Approximately 45 percent of patients will have recurrent SIBO following completion of antibiotic therapy, with recurrence rates higher in older adults, post-appendectomy and chronic use of proton pump inhibitors. In patients with early recurrence, within three months, a second course of antibiotics is given. In patients with late recurrence, beyond three months, antibiotics are provided only with positive carbohydrate breath testing. Recurrent SIBO is treatable either with the same initial antibiotic or an alternating antibiotic. If no improvement of symptoms following two courses of treatment, the clinician should consider alternative diagnoses.
Diagnoses that produce chronic diarrhea should be in the differential and investigated during the evaluation of small intestinal bacterial overgrowth. Irritable bowel syndrome (IBS), celiac disease (CD), and inflammatory bowel disease (IBD) all have considerable overlap with SIBO. Irritable bowel syndrome has recurrent abdominal pain, which is related to bowel movements and associated with a change in stool frequency or appearance. Celiac disease and SIBO have similar clinical symptoms; however, celiac disease will have positive celiac serologies and a negative carbohydrate breath test. Both Crohn disease and SIBO have patchy mucosal inflammation. However, Crohn disease additionally could demonstrate transmural inflammation and granulomas on biopsy and perianal involvement with anal fissures and fistulas.
Prognosis is serious and depends on the etiology of the underlying condition, which is causing small intestinal bacterial overgrowth.
Severe chronic small intestinal bacterial overgrowth can result in significant weight loss and severe malnutrition, which can lead to substantial morbidity and mortality. Early recognition of SIBO can treat the maldigestion of nutrients and prevent malnourishment. If left untreated, SIBO can lead to intestinal failure.
Patients with unexplained chronic diarrhea or signs and symptoms of significant malnutrition should obtain a referral to a gastroenterologist for further evaluation.
Any patients diagnosed with small intestinal bacterial overgrowth should have additional testing to determine etiology and treatment against the underlying condition to prevent recurrent SIBO. Treatment of disorders associated with abnormal intestinal motility, which includes Crohn disease, irritable bowel syndrome, post-radiation enteropathy, diabetes mellitus, hypothyroidism, and scleroderma, should be better optimized and well-controlled. Prokinetics can be useful as adjunctive therapy for these patients. Opioids, which decrease intestinal motility, and proton pump inhibitors, which cause achlorhydria, should be avoided in these patients. Surgical interventions can be a consideration in patients with anatomical abnormalities who have recurrent SIBO. There is limited research on chronic antibiotic prophylaxis, and probiotics have not been shown effective in prevention. However difficult to strictly adhere to, there may be a role for an elemental diet.
Small intestinal bacterial overgrowth is an under-recognized condition with significant morbidity and mortality. Optimal management of SIBO is by an interprofessional team of primary care physicians, gastroenterologists, surgeons, dieticians, pharmacists, and nurses. Early recognition leads to more favorable outcomes and can prevent severe malnutrition. Once SIBO is diagnosed, and the patient is on antibiotics, further management should be directed at the treatment of the underlying etiology to prevent further recurrences.
During initial treatment, nursing should be vigilant in monitoring treatment effectiveness and progress, as well as verifying patient compliance. The patient’s calorie intake and weight assessments should be frequently monitored during and after treatment to ensure adequate recovery from their illness. Nursing should follow all these areas and report back to the treating physician with any concerns. The pharmacist can assist with agent selection, verification of dosing parameters, and performing medication reconciliation. The pharmacist should also work directly with the clinician and nurse regarding potential drug-condition interactions (e.g., opioids, PPIs). SIBO management requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level V] The overall outcome is dependent on the management of the underlying condition. If the etiology is not well managed, the overall prognosis is grave. [Level II]
|||Khoshini R,Dai SC,Lezcano S,Pimentel M, A systematic review of diagnostic tests for small intestinal bacterial overgrowth. Digestive diseases and sciences. 2008 Jun; [PubMed PMID: 17990113]|
|||Bures J,Cyrany J,Kohoutova D,Förstl M,Rejchrt S,Kvetina J,Vorisek V,Kopacova M, Small intestinal bacterial overgrowth syndrome. World journal of gastroenterology. 2010 Jun 28; [PubMed PMID: 20572300]|
|||Vantrappen G,Janssens J,Hellemans J,Ghoos Y, The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. The Journal of clinical investigation. 1977 Jun; [PubMed PMID: 864008]|
|||Roland BC,Ciarleglio MM,Clarke JO,Semler JR,Tomakin E,Mullin GE,Pasricha PJ, Low ileocecal valve pressure is significantly associated with small intestinal bacterial overgrowth (SIBO). Digestive diseases and sciences. 2014 Jun; [PubMed PMID: 24795035]|
|||Riordan SM,McIver CJ,Wakefield D,Duncombe VM,Thomas MC,Bolin TD, Small intestinal mucosal immunity and morphometry in luminal overgrowth of indigenous gut flora. The American journal of gastroenterology. 2001 Feb; [PubMed PMID: 11232696]|
|||Jones RM,Neish AS, Recognition of bacterial pathogens and mucosal immunity. Cellular microbiology. 2011 May; [PubMed PMID: 21352463]|
|||Choung RS,Ruff KC,Malhotra A,Herrick L,Locke GR 3rd,Harmsen WS,Zinsmeister AR,Talley NJ,Saito YA, Clinical predictors of small intestinal bacterial overgrowth by duodenal aspirate culture. Alimentary pharmacology [PubMed PMID: 21395630]|
|||Bouhnik Y,Alain S,Attar A,Flourié B,Raskine L,Sanson-Le Pors MJ,Rambaud JC, Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome. The American journal of gastroenterology. 1999 May; [PubMed PMID: 10235214]|
|||Kirsch M, Bacterial overgrowth. The American journal of gastroenterology. 1990 Mar; [PubMed PMID: 2178395]|
|||Hoog CM,Lindberg G,Sjoqvist U, Findings in patients with chronic intestinal dysmotility investigated by capsule endoscopy. BMC gastroenterology. 2007 Jul 18; [PubMed PMID: 17640373]|
|||Greenson JK, The biopsy pathology of non-coeliac enteropathy. Histopathology. 2015 Jan; [PubMed PMID: 25234408]|
|||Quigley EM,Abu-Shanab A, Small intestinal bacterial overgrowth. Infectious disease clinics of North America. 2010 Dec; [PubMed PMID: 20937459]|
|||Lakhani SV,Shah HN,Alexander K,Finelli FC,Kirkpatrick JR,Koch TR, Small intestinal bacterial overgrowth and thiamine deficiency after Roux-en-Y gastric bypass surgery in obese patients. Nutrition research (New York, N.Y.). 2008 May; [PubMed PMID: 19083422]|
|||Bongaerts GP,Tolboom JJ,Naber AH,Sperl WJ,Severijnen RS,Bakkeren JA,Willems JL, Role of bacteria in the pathogenesis of short bowel syndrome-associated D-lactic acidemia. Microbial pathogenesis. 1997 May; [PubMed PMID: 9160298]|
|||Schnabl B,Brenner DA, Interactions between the intestinal microbiome and liver diseases. Gastroenterology. 2014 May; [PubMed PMID: 24440671]|
|||Rezaie A,Buresi M,Lembo A,Lin H,McCallum R,Rao S,Schmulson M,Valdovinos M,Zakko S,Pimentel M, Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. The American journal of gastroenterology. 2017 May; [PubMed PMID: 28323273]|
|||Ghoshal UC,Ghoshal U,Das K,Misra A, Utility of hydrogen breath tests in diagnosis of small intestinal bacterial overgrowth in malabsorption syndrome and its relationship with oro-cecal transit time. Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology. 2006 Jan-Feb; [PubMed PMID: 16567886]|
|||Corazza GR,Menozzi MG,Strocchi A,Rasciti L,Vaira D,Lecchini R,Avanzini P,Chezzi C,Gasbarrini G, The diagnosis of small bowel bacterial overgrowth. Reliability of jejunal culture and inadequacy of breath hydrogen testing. Gastroenterology. 1990 Feb; [PubMed PMID: 2295385]|
|||Shah SC,Day LW,Somsouk M,Sewell JL, Meta-analysis: antibiotic therapy for small intestinal bacterial overgrowth. Alimentary pharmacology [PubMed PMID: 24004101]|
|||Pimentel M,Chang C,Chua KS,Mirocha J,DiBaise J,Rao S,Amichai M, Antibiotic treatment of constipation-predominant irritable bowel syndrome. Digestive diseases and sciences. 2014 Jun; [PubMed PMID: 24788320]|
|||Lauritano EC,Gabrielli M,Scarpellini E,Lupascu A,Novi M,Sottili S,Vitale G,Cesario V,Serricchio M,Cammarota G,Gasbarrini G,Gasbarrini A, Small intestinal bacterial overgrowth recurrence after antibiotic therapy. The American journal of gastroenterology. 2008 Aug; [PubMed PMID: 18802998]|
|||Lembo A,Pimentel M,Rao SS,Schoenfeld P,Cash B,Weinstock LB,Paterson C,Bortey E,Forbes WP, Repeat Treatment With Rifaximin Is Safe and Effective in Patients With Diarrhea-Predominant Irritable Bowel Syndrome. Gastroenterology. 2016 Dec; [PubMed PMID: 27528177]|
|||Ghoshal UC,Shukla R,Ghoshal U, Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome: A Bridge between Functional Organic Dichotomy. Gut and liver. 2017 Mar 15; [PubMed PMID: 28274108]|
|||Losurdo G,Marra A,Shahini E,Girardi B,Giorgio F,Amoruso A,Pisani A,Piscitelli D,Barone M,Principi M,Di Leo A,Ierardi E, Small intestinal bacterial overgrowth and celiac disease: A systematic review with pooled-data analysis. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 2017 Jun; [PubMed PMID: 28191721]|
|||Shah A,Morrison M,Burger D,Martin N,Rich J,Jones M,Koloski N,Walker MM,Talley NJ,Holtmann GJ, Systematic review with meta-analysis: the prevalence of small intestinal bacterial overgrowth in inflammatory bowel disease. Alimentary pharmacology [PubMed PMID: 30735254]|
|||Ziegler TR,Cole CR, Small bowel bacterial overgrowth in adults: a potential contributor to intestinal failure. Current gastroenterology reports. 2007 Dec; [PubMed PMID: 18377796]|
|||Bohm M,Siwiec RM,Wo JM, Diagnosis and management of small intestinal bacterial overgrowth. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2013 Jun; [PubMed PMID: 23614961]|
|||Compare D,Pica L,Rocco A,De Giorgi F,Cuomo R,Sarnelli G,Romano M,Nardone G, Effects of long-term PPI treatment on producing bowel symptoms and SIBO. European journal of clinical investigation. 2011 Apr; [PubMed PMID: 21128930]|
|||Zhong C,Qu C,Wang B,Liang S,Zeng B, Probiotics for Preventing and Treating Small Intestinal Bacterial Overgrowth: A Meta-Analysis and Systematic Review of Current Evidence. Journal of clinical gastroenterology. 2017 Apr; [PubMed PMID: 28267052]|
|||Pimentel M,Constantino T,Kong Y,Bajwa M,Rezaei A,Park S, A 14-day elemental diet is highly effective in normalizing the lactulose breath test. Digestive diseases and sciences. 2004 Jan; [PubMed PMID: 14992438]|