CME: Small Intestinal Bacterial Overgrowth
- FibonacciMD
- Jun 30
- 10 min read
What Is SIBO, and How Is It Diagnosed and Treated?
Read Article, Take Test, Get FREE 🎓CME Certificate with Valid Email
We’ll send you occasional updates. Your email stays private—never sold or shared. 😇
This article will discuss small intestinal bacterial overgrowth, or SIBO, which can cause gastrointestinal disturbances due to pathological bacterial overgrowth.
SIBO was first described in the medical literature in 1939 by Barber and Hummel.[1] In 2000, Pimentel et al. published a report showing that SIBO was present in 78% of patients with irritable bowel syndrome (IBS), and antibiotic treatment led to resolution of IBS symptoms in almost half of those treated in the study.[2] In another study, 33.8% of patients with symptomatic gastrointestinal issues were positive for SIBO.[3]
What Is SIBO? [4]
It is estimated that the human intestine contains 100 trillion bacteria which, along with viruses and fungi, make up the gastrointestinal microbiome. There are approximately 500 to 1,000 different species of bacteria in the microbiome. The numbers of bacteria increase progressively from the small intestine to the large intestine. By the time digested food arrives at the small intestine, bile and stomach acid have helped eliminate many bacterial organisms. Rapid movement of ingested food through the small intestine also serves to reduce the number of bacteria. The greater circumference and slower movement of partially digested food in the large intestine allows many more bacteria to survive there. SIBO occurs when pathogenic bacteria replace normal flora which may result in abdominal distension, bloating, diarrhea, gas formation,[4] or constipation. Pseudomonas aeruginosa, Escherichia coli, Acenetobacter lwoffii, Staphylococcus species, Klebsiella pneumoniae, Streptococcus species, Acinetobacter baumannii, Enterococcus faecalis, and Enterococcus faecium were found to be the dominant bacteria in SIBO patients in one study.[5]
The actual prevalence of SIBO in the general population has a wide variation in various studies, from 1% to 40%, which may be due to diagnostic test performance, age range of the subjects, dietary differences, and the ethnicity of the subjects tested.[5]
Risk Factors
Risk factors for SIBO include anatomical and motility disorders in the small intestine, diabetic enteropathy, underlying connective tissue disease, chronic opiate use, diverticula, small bowel adhesions, and blind loop syndromes. These conditions may lead to intestinal stasis and can be caused by surgery, fistulas, diverticula, motility disorders, and inflammatory diseases, such as Crohn’s disease. Cecal valve incompetence where large intestine contents reflux back into the ileum can also be a precipitating factor. Drugs such as antidepressants and anticholinergics, which can impair intestinal motility, can increase the risk of SIBO.[6] Impairments in normal bacteria reduction mechanisms such as reduced bile output in pancreatitis or hypochlorhydria with reduced stomach acid caused by chronic use of proton pump inhibitors (PPIs) can also increase the risk of SIBO. Additionally, SIBO is more prevalent in elderly patients and women.
In one study, small bowel dysmotility was shown to more than triple the risk of SIBO. As previously mentioned, the first study to examine the relationship of SIBO and irritable bowel syndrome reported 78% of IBS patients also had SIBO.[2] However, a later meta-analysis reported the SIBO incidence in irritable bowel patients to be a much lower 22.3%.[7] Another meta-analysis reported that extended PPI use increased the risk of SIBO by 70%.[8]
Testing
The “gold standard” test for SIBO is a bacterial culture of small bowel aspirate. A positive test consists of a bacterial count equal to or more than 1,000 colony-forming units per milliliter (CFU/mL). However, the invasive nature of the test, which requires tube insertion into the small intestine, combined with possible contamination by oropharyngeal flora that can invalidate the test, has limited its use. Instead, breath tests have emerged as the preferred diagnostic tests.[4]
In patients with SIBO, small bowel pathogenic bacteria produce methane and hydrogen gases. Most of the gas is rapidly eliminated with passing flatus. However, approximately 20% of the gases are absorbed by the lung and then subsequently exhaled, allowing for measurement during breath testing.
Methanobrevibacter smithii is the predominant organism that produces methane. These organisms are not considered true bacteria but are Archaea, a separate domain (Archaea are one-celled but have different RNA and lipids in their cell membrane than bacteria). The American College of Gastroenterology guidelines suggest that a more proper nomenclature, when methane is the predominant gas, is intestinal methanogen overgrowth (IMO) as opposed to SIBO.[9] (The use of IMO nomenclature is not uniform in the literature, and for the rest of this article, IMO will be called by the older term methane-positive SIBO.) Methane-positive SIBO patients are five times more likely to suffer constipation than hydrogen-positive SIBO patients.[10]
In standard breath tests the patient drinks either a glucose or lactulose solution. Breath samples are then measured for hydrogen and methane, which were created by bacteria or Archaea fermenting the compounds. Glucose is superior for detecting bacterial overgrowth in the proximal part of the small intestine, while lactulose is thought to be better for detecting bacterial overgrowth in the distal part of the small intestine, as it is absorbed more slowly. Guidelines state that a rise in breath hydrogen levels of ≥ 20 ppm (parts per million) 90 minutes after ingestion of glucose or lactulose should be considered a positive result. A rise in exhaled breath methane levels by ≥ 10 ppm should be considered a methane-positive result.[4] Spot testing of methane levels in fasting patients has also been found to be an accurate way of diagnosing and performing follow-up testing of methane-positive SIBO patients, instead of having to complete an entire breath testing protocol.[11] For breath testing, patients should not be taking antibiotics, probiotics, antimotility agents, or antacids and should be fasting for the exam.[4] Stopping PPIs is not necessary.[10] A bland diet avoiding high fiber and complex carbohydrates for one to two days before the exam is also recommended.[4] Smoking can increase hydrogen in the exhaled breath and increase intestinal transit time and should be stopped on the day of the exam.[10] Deviating from the testing protocol can affect the accuracy of the test.
There can be false positives and negatives in breath testing. Hydrogen breath tests are dependent on the patient’s oro-cecal transit time. If transit time is rapid, such as in those with previous upper abdominal surgery, the glucose breath test may lead to false positive results. This would be due to the glucose or lactulose reaching the colon too rapidly and colonic bacteria fermenting the carbohydrates, producing hydrogen. Some researchers have suggested use of gastrointestinal tract scintigraphy, which measures the rate of intestinal movement of food, during a breath test to help decrease the false positive rate in high-risk patients with rapid oro-cecal transit time.[12] Conditions that slow intestinal transit time, such as achalasia and gastroparesis, may lead to false negative results due to delay of glucose or lactulose reaching the majority of small intestine in time to give a positive result. Methane breath tests are generally less affected by intestinal transit times.[13]
One meta-analysis reported that the sensitivities of the hydrogen lactulose and glucose breath tests were 42% and 54.5% with specificities of 70.6% and 83.2%, respectively.[14] It is generally felt that testing for both methane and hydrogen increases testing accuracy.[15]
In patients with SIBO, as there may be malabsorption, vitamin B12 and fat-soluble vitamins A, D, E, and K may also be decreased, and blood levels should be measured.[4]
Researchers have attempted to examine SIBO metabonomics. Metabonomics is the study of small metabolites in a biological system known as the metabolome. Using proton nuclear magnetic resonance spectroscopy on body fluids allows identification of an individual’s “metabolic fingerprint”. This may eventually allow for more specific diagnoses of different SIBO subtypes, but it is only experimental at the present time.[16,17]
Treatment
Antibiotics
Antibiotics are considered the first-line treatment for SIBO to eradicate the pathogenic strains. Rifaximin is typically the preferred medication and is a non-absorbable antibiotic which acts against Gram-positive and Gram-negative aerobic and anaerobic bacteria. Rifaximin can also preserve normal colonic flora and may increase the relative abundance of SIBO-protective lactobacilli and bifidobacteria in the gut.[4] There are a number of different dosage regimens, but 1200 mg to 1,650 mg per day for 14 days in adults is commonly recommended.[18] There is some evidence that the higher doses are more effective than the lower dose regimen.[19] Rifaximin is FDA-approved for IBS treatment, but not specifically approved for SIBO, and thus is considered an off-label use of the drug.
Combination therapy of rifaximin and neomycin for patients with methane-positive breath tests may be more effective than rifaximin alone. In one study, rifaximin and oral neomycin combination therapy led to 85% of the subjects having a clinical improvement and 87% having a negative repeat methane breath test. Rifaximin solo therapy resulted in only 56% of subjects having clinical improvement and 28% converting to a negative methane breath test. Neomycin therapy alone was also not as effective as combination therapy.[20]
Other drugs that may be used to treat SIBO include metronidazole, tetracyclines, amoxicillin/clavulanate, and fluoroquinolones.[4]
Probiotics
Probiotics, by introducing healthy bacteria, have been recommended for treating SIBO. A probiotic is a food or supplement that contains live bacteria. In contrast, a prebiotic is a non-absorbable high-fiber food that encourages the growth of probiotics. One meta-analysis reported that probiotics could not prevent SIBO but were helpful in eliminating harmful bacteria from the gut.[21] However, another study found a correlation of brain fog, D-lactic acidosis, and SIBO with probiotic use and postulated that in certain cases, probiotics could make SIBO worse.[22] Finally, one study, published only in abstract form as a scientific meeting presentation, reported that recent probiotic use in patients with suspected SIBO was associated with an increase in methane-positive lactulose breath tests. This suggests that probiotic use may possibly predispose to overgrowth of methanogenic bacteria.[23]
Dietary Therapy
Dietary therapy may be helpful in the treatment of SIBO patients. In SIBO, gut bacteria or Archaea ferment carbohydrates, such as fructose, lactose, oligosaccharides, disaccharides, and monosaccharides, which may result in gas formation, bloating, flatulence, and abdominal pain. The FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) diet is the most widely recommended as it reduces the amount of carbohydrates fermenting in the gut. This decreases nutrients for the gut bacteria, which can limit their growth. In the FODMAP diet plan, after initiation and improvement, there is a phase where foods are reintroduced slowly to see which, if any, worsen symptoms and can be avoided in the future.[4] For more information on the FODMAP diet, click here.[24]
There are some data that the FODMAP diet can reduce some of the symptoms of IBS, but the data are of low quality, and better studies are needed. The FODMAP diet is meant to be used as short-term therapy because there is the possibility of causing a nutritional imbalance with long-term use, and data is lacking on long-term efficacy.[25]
In SIBO therapy, an elemental diet is sometimes recommended. This consists of oral enteral liquids which contain proteins, fats, and carbohydrates in their basic forms of amino acids, short-chain triglycerides, and short-chain maltodextrins, with additional vitamins, minerals, and electrolytes. An elemental diet allows easy absorption of nutrients and rests the gut. Most absorption of this diet occurs in the proximal small intestine, which limits bacterial nutrients getting to more distal parts of the small bowel.[4] In one study of elemental diets, 80% of subjects normalized their lactulose breath test within two weeks, and a total of 85% of the subjects’ breath tests were normalized by 3 weeks. About 11% of the subjects dropped out of the study as they could not tolerate the diet.[26]
Herbal Supplements
Using herbs with known antimicrobial activity has also been trialed to treat SIBO. In one experiment, subjects were either given rifaximin tablets or herbal supplements for four weeks. In rifaximin non-responders, subjects were either given triple antibiotics (clindamycin, metronidazole, and neomycin) or herbal supplements for an additional four weeks. There was no statistically significant difference in the response rate between herbal therapy and antibiotic therapy both at four and eight weeks.[4,27] It should be noted that data on herbal supplements are extremely limited, and ingredients of various supplements may vary and are not FDA approved for treating SIBO.
A study compared subjects with SIBO eating a FODMAP diet to another group where L-glutamine was added to the FODMAP diet.[27] L-glutamine is an amino acid that can improve gut microbiota and intestinal barrier integrity through several mechanisms, including control of pathogen colonization and overgrowth, increased production of secretory immunoglobulin A, and formation of tight junctions between enterocytes (intestinal cells).[26] It was reported that the methane-positive SIBO group had significant improvement in clinical symptoms with the addition of the L-glutamine, while the hydrogen-positive SIBO group did not. However, there was no objective finding of improvement of breath test results.[28] Another study compared antibiotic plus FODMAP diet to another group which also received herbal medications, L-glutamine, prebiotics, and probiotics. It was reported that only the methane-positive group had a subjective improvement in clinical symptoms with the ingestion of the nutritional additives.[29]
Fecal Microbiota Transplants
In one study, 55 patients with SIBO were given either capsules containing normal donor fecal material or a placebo. There were statistically significant symptom improvements in the patients given fecal transplant compared to those given placebo. It was also reported that there was a significant drop in the hydrogen levels during a lactose breath test in the transplant group after therapy, not seen in the control group.[30]
Another study looking at subjects with chronic constipation compared giving fecal microbiota transplants to patients both with SIBO and without SIBO. They reported that the transplants worked better in patients with SIBO than those without SIBO. 56% of patients with SIBO were cured, and 81% had an improved clinical response. There were significantly improved abdominal, rectal, and defecation symptoms in the SIBO group, and quality of life scores improved with significant decreases in abdominal discomfort, anxiety, and psychosocial discomfort.[31]
Treatment Failure
Up to 40% of patients with SIBO will not respond to antibiotic therapy, and in those cases, other causes of abdominal symptoms, such as lactose intolerance or other gastrointestinal disorders, should be considered.[4] Repeat breath testing may be necessary to confirm resolution. Additional treatments, such as dietary therapy, may be helpful to attempt to improve symptoms and prevent recurrences.[24,25]
Summary
SIBO is a relatively common disease leading to abdominal symptoms, especially in patients with risk factors such as IBS or PPI use. Breath testing for hydrogen and methane has made diagnosis of this disorder much easier than obtaining a jejunal aspirate for culture.
Antibiotics are the mainstay of treatment, but dietary therapy such as the FODMAP diet, elemental diet, or selected supplements have demonstrated some efficacy. It is possible that fecal microbiota transplants may become a standard therapy in the future.
Author’s note: Thank you to Dr. Theodor Feigelman for editing this article.
🎓 Want Free CME Credit for This Article?
Take the quiz now at www.FibonacciMD.app. It only takes a few minutes!
Your certificate will be emailed to you after you pass the quiz and complete a short evaluation
We’ll send you occasional updates. Your email stays private—never sold or shared. 😇
✅ Earn Free CME Credit for Reading This Article
Eligible for 0.5 PRA Category 1 Credit
Click the button below to take a short quiz.
A valid email is required to send your certificate.
We’ll send you occasional updates. Your email stays private—never sold or shared. 😇