INTRODUCTION —
Small intestinal bacterial overgrowth (SIBO) is a condition in which colonic and oropharyngeal bacteria are found in excess in the small intestine. This overabundance of microorganisms can result in intestinal symptoms and, in extreme cases, malabsorption. The majority of patients with SIBO present with bloating, flatulence, abdominal discomfort, diarrhea, or, in the case of intestinal methanogen overgrowth (IMO), constipation. This topic will review the management of SIBO. The etiology, pathogenesis, clinical manifestations, and diagnosis of SIBO are presented separately. (See "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis".)
INITIAL APPROACH —
The mainstay of therapy for SIBO includes treating the underlying cause (where applicable), antibiotics, correcting gastrointestinal dysmotility, and treating nutritional deficiencies.
Antibiotic therapy — The first-line treatment in the management of SIBO involves using antibiotic therapy. Antibiotic therapy is typically begun after confirming SIBO by breath test or duodenal aspirate and culture. The selection of other antimicrobial regimens is based on the pattern of bacterial overgrowth, the prevalence of risk factors for drug-resistance (recent or repeated prior exposure), relevant antibiotic allergies, and cost [1]. It is unnecessary to repeat breath testing if symptoms resolve with treatment. (See "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis", section on 'Carbohydrate breath test'.)
●Small intestinal bacterial overgrowth – In patients with small intestinal bacterial overgrowth, we use rifaximin for 14 days [2,3]. Rifaximin is a nonabsorbable rifamycin derivative. It is well tolerated and has been demonstrated to be effective in the treatment of SIBO [3-9]. However, the high cost of rifaximin has limited its use.
●Intestinal methanogen overgrowth (IMO) – In patients with IMO, we use a combination of neomycin 500 mg twice daily and rifaximin 550 mg three times daily for 14 days [10,11]. (See "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis", section on 'Carbohydrate breath test'.)
Alternative antibiotics for treatment of SIBO include trimethoprim-sulfamethoxazole, norfloxacin, ciprofloxacin, metronidazole, tetracycline, or amoxicillin-clavulanic acid [11]. Alternative antibiotic regimens for the treatment of SIBO are listed in the table (table 1). There are few randomized trials of antibiotics to treat bacterial overgrowth and the evidence for use of specific antibiotics is largely from observational studies [3-9]. In a systematic review and meta-analysis that included 10 studies, antibiotics were more effective than placebo for treating SIBO, with a combined breath test normalization rate of 51 versus 10 percent [3]. In this study, rifaximin was the most studied antibiotic (eight studies), with an overall breath test normalization rate of 49.5 percent (95% CI 44.0-55.1). Treatment of SIBO with high hydrogen sulfide is still under study. (See 'Society guideline links' below.)
Correction of micronutrient deficiency — Deficiencies of vitamin B12, fat-soluble vitamins, iron, thiamine, and niacin can be associated with severe SIBO and should be corrected when present. (See "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis", section on 'Laboratory findings' and "Treatment of vitamin B12 and folate deficiencies", section on 'Vitamin B12' and "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Vitamin D replacement' and "Overview of water-soluble vitamins".)
Targeting small intestinal dysmotility through treatments is expected to alleviate symptoms related to SIBO. However, the effectiveness of prokinetics and somatostatin analogues like octreotide in eradicating SIBO is limited. A systematic review and meta-analysis found that short-term administration of octreotide, which has a prokinetic effect, has shown promising results in improving abdominal symptoms and normalizing hydrogen breath tests in patients with scleroderma and SIBO [12,13].
TREATMENT RESPONSE AND RECURRENCE —
Approximately 40 percent of patients with small intestinal bacterial overgrowth (SIBO) have persistent symptoms after initial antibiotic treatment [14]. Recurrent SIBO is also frequent after antibiotic treatment. In a study involving 80 patients with SIBO, recurrence rates three, six, and nine months after successful treatment with rifaximin were 13, 28, and 44 percent, respectively [14]. Recurrence was more likely in older adults, those with a history of an appendectomy, and with chronic proton pump inhibitor use.
INADEQUATE RESPONSE TO INITIAL THERAPY OR RECURRENCE
Evaluation — Recurrent cases of SIBO may require retreatment with antibiotics. However, it is important to note that this practice is primarily based on anecdotal evidence and expert opinion. There is no agreed-upon treatment approach for recurrent SIBO therapy. We empirically treat patients with a second course of antibiotics if they have a partial improvement in symptoms or early recurrence (<3 months). For patients with recurrent symptoms ≥3 months after initial antibiotic treatment, a repeat breath test can confirm recurrence of SIBO. Patients with no improvement in symptoms after two courses of antibiotic therapy or progressive symptoms should be evaluated for alternative diagnoses. (See "Evaluation of the adult with abdominal pain" and "Approach to the adult with chronic diarrhea in resource-abundant settings".)
Subsequent antibiotic regimen — In patients with partial response to recurrent SIBO, the choice of antibiotic therapy should be guided by the patient's initial treatment regimen. Antibiotics included in the initial regimen should generally be avoided. However, patients with an inadequate initial response or recurrent SIBO after treatment with rifaximin can be retreated with a course of rifaximin or an alternative antibiotic [15]. Alternative antibiotic regimens are also summarized in the following table (table 1). Compliance with antibiotic therapy should be reinforced.
Elemental diet — We reserve the use of an elemental diet to patients who cannot tolerate antibiotics or have failed to respond to antibiotic therapy for SIBO. Limited observational data suggest that an elemental diet can induce remission of symptoms in patients with SIBO. However, elemental diets are expensive, and compliance is limited by palatability. In a retrospective study, 124 patients with methane- or hydrogen-predominant SIBO were treated exclusively with an elemental diet for at least two weeks [16]. Patients continued the diet for a total of three weeks if the breath test did not normalize by week two. At two weeks, 74 of 93 patients (80 percent) had a normal breath test. Five of 19 subjects who were treated with an elemental diet for an additional week had a normal breath test by day 22 for a cumulative response of 85 percent. Patients who normalized their breath test had a significant improvement in symptoms as compared with those with persistently abnormal breath tests (66 versus 12 percent). Fourteen patients discontinued the elemental diet and were excluded from the analysis.
PREVENTION OF RECURRENCE
Treatment of the underlying conditions predisposing to small intestinal bacterial overgrowth — It is crucial to diagnose and treat conditions that increase the risk of SIBO. This will not only correct the imbalance of gut bacteria in the small intestine but also help prevent the recurrence of SIBO (table 2). As examples, medications that can decrease intestinal motility (eg, opioids, benzodiazepines) or cause achlorhydria (eg, proton pump inhibitor) should be avoided when possible. Prokinetics are a useful adjunct in patients with SIBO due to an underlying dysmotility. In the case of iatrogenic surgical causes of SIBO and for fistulas between the proximal and distal intestine, surgery may be necessary in patients who fail to respond to antibiotics and have significant weight loss, diarrhea, and signs of malnutrition. (See "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis", section on 'Evaluation to determine the etiology'.)
Antibiotic prophylaxis in selected patients — Antibiotic prophylaxis for SIBO should be reserved for patients with ≥4 distinct and well-documented episodes within one year and risk factors for recurrent SIBO (eg, short bowel syndrome, jejunal diverticulosis). In such patients we administer antibiotics on a periodic basis (5 to 10 days out of every month or every other week). Antibiotics are changed to prevent the development of resistance to a specific drug. The frequency with which antibiotics are rotated varies from monthly to every six months. A single-center retrospective study showed that treatment of SIBO using rotating antibiotics (quinolone and azole, one after the other for 10 consecutive days per month for three months) was more effective than treatment using a single course of antibiotic [17]. The likelihood of remission (defined as negative glucose breath test after antibiotic treatment) was found to be higher in patients who received rotating antibiotics (70 percent) compared with those who received a single antibiotic (70 versus 51 percent).
Interventions with unclear role
●Low fermentation eating or a low fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) diet – FODMAPs are short-chain carbohydrates that are poorly absorbed and are osmotically active in the intestinal lumen where they are rapidly fermented by small intestinal bacteria. A diet low in FODMAPs improves bloating and gas in patients with irritable bowel syndrome, however, evidence to support a low FODMAP diet in the prevention or management of patients with SIBO are lacking. Other low fermentation diets are less restrictive and can be used more long term. (See "Obesity in adults: Dietary therapy".)
●Probiotics – There are limited data to support probiotics in the treatment of SIBO [18-22]. In a 2017 meta-analysis that included 18 studies there was no significant difference in the incidence of SIBO in patients on probiotics as compared with the control group [22]. Patients with SIBO who were treated with probiotics had higher rates of gut decontamination and decrease in breath hydrogen concentration and abdominal pain, but there was no significant improvement in diarrhea. Studies that have evaluated the use of probiotics in SIBO tend to be small and lack standardized treatment formulations. To advance our knowledge in this area, it is crucial to conduct large-scale, randomized, placebo-controlled trials that can effectively assess the optimal utilization of alternative therapies for SIBO.
●Statins – Statins have been shown to inhibit growth and production of methane in several Methanobrevibacter isolates [23]. However, studies in patients with intestinal methanogen overgrowth are lacking.
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Small intestinal bacterial overgrowth".)
SUMMARY AND RECOMMENDATIONS
●Clinical significance – Small intestinal bacterial overgrowth (SIBO) is a condition in which the small bowel is colonized by excessive aerobic and anaerobic microbes. The majority of patients with SIBO present with bloating, flatulence, abdominal discomfort, or watery diarrhea. (See 'Introduction' above.)
●Initial management – We suggest antibiotic treatment for SIBO with rifaximin (Grade 2C). In patients with intestinal methanogen overgrowth, we use a combination of neomycin and rifaximin (table 1). Adequate antimicrobial coverage can also be achieved with other antibiotic combinations. Deficiencies of vitamin B12, fat-soluble vitamins, iron, thiamine, and niacin are usually associated with severe SIBO and require supplementation when present. (See 'Antibiotic therapy' above.)
●Patients with persistent or recurrent symptoms
•Approximately 40 percent of patients with SIBO have persistent symptoms after initial antibiotic treatment and 40 percent have recurrent SIBO within nine months of antibiotic treatment. (See 'Treatment response and recurrence' above.)
•We empirically treat patients with a second course of antibiotics if they have a partial improvement in symptoms or early recurrence (<3 months). For patients with recurrent symptoms ≥3 months after initial antibiotic treatment, we perform a repeat carbohydrate breath test or small bowel aspirate culture where available to diagnose SIBO. (See 'Inadequate response to initial therapy or recurrence' above and 'Evaluation' above and "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis", section on 'Carbohydrate breath test'.)
•Patients with persistent symptoms after two courses of antibiotic therapy or progressive symptoms should be evaluated for alternative diagnoses. We reserve the use of an elemental diet to patients who cannot tolerate antibiotics or have failed to respond to antibiotic therapy for SIBO. (See 'Evaluation' above.)
●Evaluation of the underlying etiology and recurrence prevention – All patients should receive therapy directed against the underlying etiology of SIBO (table 2). We reserve antibiotic prophylaxis for SIBO for selected patients with multiple recurrences of SIBO and risk factors for recurrence (eg, short bowel syndrome, jejunal diverticulosis). (See 'Prevention of recurrence' above.)
ACKNOWLEDGMENT —
The UpToDate editorial staff acknowledges Jon Vanderhoof, MD, Rosemary Pauley-Hunter, NP-C, and Mark Pimentel, MD, FRCP(C), who contributed to earlier versions of this topic review.