SIBO (Small Intestinal Bacterial Overgrowth) is a condition where excessive bacteria accumulate in the small intestine, causing symptoms like bloating, gas, and abdominal pain. This comprehensive clinical guideline from the American College of Gastroenterology provides evidence-based recommendations for diagnosing and treating SIBO, including the use of breath testing and antibiotics. The guideline also introduces a new term, IMO (Intestinal Methanogen Overgrowth), to more accurately describe overgrowth of methane-producing organisms, which are archaea rather than bacteria. Key recommendations include using glucose or lactulose breath tests for diagnosis in IBS patients and using antibiotics to eradicate overgrowth and resolve symptoms.
Small intestinal bacterial overgrowth, commonly known as SIBO, has been recognized as a medical condition for many decades. The fundamental concept is that the normal small bowel (small intestine) has lower levels of microbial colonization compared with the colon (large intestine), and this normal balance becomes significantly altered in SIBO.
In simple terms, SIBO is defined as the presence of excessive numbers of bacteria in the small bowel that cause gastrointestinal (GI) symptoms. These bacteria are usually coliforms, which are typically found in the colon and include predominantly Gram-negative aerobic and anaerobic species that ferment carbohydrates and produce gas.
Since the late 1990s, there has been a resurgence in SIBO research, which has been further enhanced by the increasing knowledge of the gut microbiome and its roles in human health and disease. A series of articles have linked SIBO to many conditions, including:
Although these findings are important, a recent consensus document identified a number of strengths and weaknesses in the published work in this area. As such, an effort has been underway to re-evaluate the criteria for the diagnosis of SIBO and define the optimal methods for diagnostic testing to identify this condition.
Furthermore, treatment for SIBO has been largely empirical, meaning it has been based on clinical experience rather than rigorous scientific trials, and has not undergone the scrutiny of sponsored clinical trials. This guideline provides an evidence-based evaluation of the literature and assesses the current unmet needs in SIBO research.
SIBO can be most inclusively defined as a clinical syndrome of GI symptoms caused by the presence of excessive numbers of bacteria within the small intestine. This definition implies that there must be a measurable and excessive bacterial burden within the small bowel, and that this microbial overgrowth has resulted in specific GI signs and/or symptoms.
For example, the pathologic fermentation of nutrients that would ordinarily be completely absorbed in the small intestine could lead to the production of excess gas and bloating. The objective measurement of bacteria in the small intestine was initially achieved through quantitative culture of aspirates acquired from the proximal small bowel, similar to how a urine culture is used to diagnose a urinary tract infection.
However, the threshold cutoff for the definition of a positive culture has been controversial, both in the published literature and among experts in the field. The most recent North American Consensus found that the literature points more accurately to a bacterial colony count of ≥10³ colony-forming units per milliliter (CFU/mL) in a duodenal/jejunal aspirate as diagnostic of SIBO. This is based on a collation of the literature among normal subjects in trials.
Evidence suggests that the most common symptoms described in patients with SIBO include:
These symptoms are prevalent in more than two-thirds of patients. In severe cases, nutritional deficiencies including vitamin B12, vitamin D, and iron deficiencies can occur, but in most cases, these are subtle or undetectable. Some patients may also manifest fatigue and poor concentration.
However, no single symptom can be specifically attributed to SIBO. Symptoms often masquerade as other diagnoses such as IBS, functional diarrhea, functional dyspepsia, or bloating. This is due in part to the varied presentation of patients with SIBO and the number of underlying risk factors that can lead to the development of SIBO.
For example, in a patient with chronic pancreatitis, it is difficult to determine whether diarrhea results from exocrine insufficiency (lack of digestive enzymes) or from coexistent SIBO, and to what extent symptoms are related to pancreatic insufficiency versus SIBO. Similarly, in patients with Crohn's disease, particularly those having undergone ileocecal valve resection, symptoms of abdominal pain, bloating, and diarrhea could result from SIBO versus active inflammation, bile acid malabsorption, or postoperative strictures.
One study by Jacobs et al. obtained aerobic and anaerobic duodenal cultures from subjects undergoing antroduodenal manometry (a test that measures pressure in the stomach and duodenum) and compared 38 subjects with culture-positive SIBO to 74 subjects with culture-negative SIBO. The study reported no differences in the intensity, frequency, and duration of abdominal pain or in bloating, fullness, belching, indigestion, nausea, vomiting, diarrhea, and gas between the two groups.
Therefore, close attention should be paid not only to a patient's symptom profile but also to risk factors for SIBO and any history of previous attempts to treat other underlying conditions when evaluating SIBO as a possible diagnosis.
There are two main approaches to diagnosing SIBO: breath testing and small bowel aspiration with culture. Each method has its own advantages, limitations, and specific criteria for interpretation.
The signs and/or symptoms of SIBO can arise from the malabsorption of nutrients, alteration in intestinal permeability, inflammation, and/or immune activation that arises from the pathologic bacterial fermentation within the small bowel. Such symptoms can include, but may not be limited to, nausea, bloating, flatulence, abdominal distension, abdominal cramping, abdominal pain, diarrhea, and/or constipation.
In extreme cases, signs can include steatorrhea (fatty stools), weight loss, anemia, deficiencies in fat-soluble vitamins, and/or mucosal inflammation of the small bowel. These are usually associated with extraordinary causes of SIBO such as iatrogenic (postsurgical blind loop) or scleroderma.
Quantitative measurement of breath hydrogen and/or methane is a relatively inexpensive, noninvasive, easy, and widely available test. Since the clinical definition of SIBO is unclear in the absence of validated patient-reported outcomes, the use of breath testing for SIBO is recognized as a key concept but not a formal graded recommendation.
Newer mail-in kits are now available for home testing for patients who are not able to travel or who live in remote locations. Often these kits are directed to laboratories with Clinical Laboratory Improvement Amendments (CLIA) certification and as such have more stringent validation and calibration supervision compared with clinicians' offices. However, diet precautions before the test, substrate ingestion, and breath test collection occur in a home setting that may not be strictly controlled.
The premise of breath tests is that human cells are incapable of producing hydrogen and methane gases. Consequently, if these gases can be detected in breath samples, it must signify another source, such as the fermentation of carbohydrates by microbes in the gut, their subsequent absorption into the bloodstream, and their expiration through the lungs.
This principle has led to the development of several carbohydrate substrate-based breath tests. Here, after ingestion of a carbohydrate load and its exposure to bacteria, the sugar is rapidly fermented to produce hydrogen gas along with short-chain fatty acids. Methanogenic archaea (single-celled microorganisms that are distinct from bacteria) in turn use hydrogen as a substrate for the production of methane.
A rise in the concentrations of hydrogen in breath samples facilitates a diagnosis of SIBO, whereas the North American Consensus recommended that the presence of methane levels ≥10 ppm (parts per million) is diagnostic of methanogenic overgrowth. However, some experts recommend a rise of 10 ppm in methane levels.
Before breath testing, it is recommended that patients:
The North American Consensus recommends administering 75-g glucose or 10-g lactulose, either taken with or followed by 1 cup of water (approximately 250 mL). The breath samples should be measured for both hydrogen and methane.
An increase in hydrogen concentrations of ≥20 ppm from baseline within 90–120 minutes is recommended to be diagnostic of SIBO. Although methane is increasingly important and recognized, it creates a nomenclature problem in the SIBO framework.
For methane, a concentration of ≥10 ppm at any point during the test is indicative of methanogen colonization. However, methanogens are not "bacteria" (representing the "B" in SIBO) but belong to the domain Archaea and may also overgrow in the colon, not just the small intestine. As such, the guideline authors have proposed a new term, intestinal methanogen overgrowth (IMO), for methanogens rather than SIBO.
Irrespective of the nomenclature, a change in or measured level of hydrogen or methane that remains below the threshold levels noted above should be considered a negative test. When using lactulose as a substrate, an initial peak from bacterial overgrowth in the small intestine followed by a second peak from colonic bacterial fermentation has been described. However, per the new consensus statement, a second peak is not required, but the first peak must occur within 90 minutes of substrate administration for the test to be considered positive.
According to a systematic review by Khoshini et al., the sensitivity of lactulose breath testing has ranged from 31% to 68% and specificity has ranged from 44% to 100%, whereas the sensitivity of glucose breath testing has varied from 20% to 93% and specificity from 30% to 86% when compared with cultures of aspirates from the small bowel.
Recently, the use of fructose as a monosaccharide substrate for persons with diabetes with suspected SIBO has been evaluated because a 75-g glucose load can cause acute hyperglycemia and gut dysmotility and possibly impact the breath test results. In this study, when compared with duodenal aspirates, the use of a fructose solution as the substrate in persons with diabetes yielded similar sensitivity, specificity, and diagnostic accuracy (48%, 71%, and 58%, respectively) for the diagnosis of SIBO when compared with glucose solution in persons without diabetes. Although not studied, lactulose may be preferred for diabetic subjects as a nonabsorbed carbohydrate.
In addition to hydrogen and methane, hydrogen sulfide (H₂S) is another gas produced by gut bacteria, but a commercial testing system is not yet available. A recent study evaluated the role of H₂S in patients undergoing a workup for SIBO. However, a cutoff value for diagnosis of SIBO using H₂S gas needs to be validated and its utility determined.
Small bowel aspirate and culture is often considered the gold standard for the diagnosis of SIBO. Standardized techniques for aseptic collection of small bowel aspirate samples are lacking, as methods differ regarding the placement of the device for sample aspiration, the amount of fluid collected, and sample handling and subsequent culture.
In general, during an upper endoscopy, a deep duodenal intubation can be achieved while minimizing suction during the insertion of the scope through mouth and stomach and preventing cross-contamination of secretions from outside the duodenum. In one technique, a 2-mm Liguory catheter (COOK Medical, Bloomington, IN) with multiple side holes is passed through the biopsy channel of an upper endoscope into the third and fourth portions of the duodenum.
Using gentle suction, approximately 3–5 mL of duodenal fluid is aspirated, and the specimen is sent to a microbiology laboratory for aerobic and anaerobic culture. Wearing sterile gloves both by the endoscopist and assistant when assembling the catheter and collecting samples, and placing a sterile cap on the syringe, are all key components for proper specimen collection and handling.
Once obtained, the specimen should be promptly transferred to a microbiology laboratory with rapid processing for aerobic and anaerobic cultures. It is important to communicate with the laboratory personnel regarding use of appropriate media and not to report results as positive or negative but to describe the growth of organisms as a precise colony count in CFU/mL.
Historically, a level of ≥10⁵ CFU/mL had been used for identifying pathological bacterial infection in humans, including a diagnosis of SIBO. However, in the case of SIBO, this cutoff appears too stringent and lacks validation. Healthy controls have <10³ CFU/mL in the small bowel, and concentrations above 10⁵ CFU are almost exclusively seen in patients with gastrectomy (stomach removal surgery). These levels were often from patients with Billroth I or II procedures (types of stomach surgery) and blind loops or segments of intestinal stasis out of continuity with the digestive flow.
Therefore, a concentration of ≥10³ CFU/mL is now generally considered diagnostic of SIBO and has been recommended by the North American Consensus.
Diagnosis of SIBO using small bowel aspiration and culture is time-consuming, expensive, and is an invasive procedure which requires sedation and carries the usual risks of endoscopy, but it is technically simple and can be widely performed outside of specialized referral centers or research environments. In one study, the diagnostic agreement of small bowel aspirates with breath testing was approximately 65%, indicating that using one testing method may not definitively diagnose SIBO and that additional testing may be necessary, particularly in patients with persistent symptoms and a high likelihood of SIBO.
Although published data are limited, there is a growing list of studies assessing SIBO by 16S ribosomal RNA (rRNA) gene sequencing in a cohort of subjects with IBS. In one study, sequencing of a small cohort of subjects revealed lower microbial diversity in the duodenum in subjects with IBS compared with subjects without IBS.
The most significant findings were:
In another study, Kerckhoffs et al. found higher levels of Pseudomonas in the small bowel of subjects with IBS compared with healthy controls. These results were mirrored in stool samples from the same cohort.
In the largest study to date, sequencing was able to validate SIBO as >10³ CFU/mL by culture on MacConkey agar based on correlation to symptoms, sequencing, and breath testing results. In the same study, using a cutoff of >10³ CFU/mL also correlated with a positive hydrogen breath test (i.e., a rise in hydrogen ≥20 ppm above baseline) at 90 minutes and also correlated with the clinical symptoms of bloating and urgency.
Another study sequenced microbes in duodenal samples and rectal biopsies from subjects with IBS and controls and also found higher numbers of bacteria in the small bowel in subjects with IBS. However, a study of jejunal aspirates using culture and PCR of 16S rRNA genes found no significant correlation between glucose breath test results and bacterial levels. Large-scale studies are currently underway to evaluate this further.
It is recognized that the current breath tests have low sensitivity and specificity and that additional validation studies are needed for standardization. The lactulose breath test has been criticized for high false-positive values (because of the accelerated transit and colonic fermentation in some individuals), and the glucose breath test has been criticized for being absorbed in the proximal duodenum and therefore having low sensitivity for detecting distal SIBO—in other words, missing overgrowth in the distal small bowel.
A unique orally ingested capsule technology is also under development that can measure in vivo hydrogen and carbon dioxide after ingestion of a carbohydrate meal and may provide a better alternative to current breath hydrogen measurement techniques. Additional capsule technologies that can sample small bowel bacteria (small bowel capsule detection system) are also emerging, and these technologies could provide a more direct and accurate evaluation of SIBO.
The guideline provides specific recommendations for when to test for SIBO in various patient populations. These recommendations are graded based on the quality of evidence and the strength of the recommendation.
We suggest the use of breath testing (glucose hydrogen or lactulose hydrogen) for the diagnosis of SIBO in patients with IBS (conditional recommendation, very low level of evidence).
IBS is one of the most commonly evaluated conditions with ties to SIBO, which has allowed this association to be graded in this guideline. Although the rate of SIBO in IBS is debated, meta-analyses suggest that up to 78% of IBS subjects suffer from SIBO. Although there remains a question of cause or effect in IBS, there is little controversy that a subset of subjects with IBS have SIBO.
We suggest using glucose hydrogen or lactulose hydrogen breath tests for the diagnosis of SIBO in symptomatic patients with suspected motility disorders (conditional recommendation, very low level of evidence).
Motility disorders affect the normal movement of food through the digestive tract. When motility is impaired, bacteria can accumulate in the small intestine, leading to SIBO.
We suggest testing for SIBO using glucose hydrogen or lactulose hydrogen breath tests in symptomatic patients (abdominal pain, gas, bloating, and/or diarrhea) with previous luminal abdominal surgery (conditional recommendation, very low level of evidence).
Surgery on the gastrointestinal tract can alter the normal anatomy and motility, creating conditions that favor bacterial overgrowth.
We suggest against the use of breath testing for the diagnosis of SIBO in asymptomatic patients on PPIs (conditional recommendation, very low level of evidence).
Proton pump inhibitors are medications that reduce stomach acid production. While they are commonly used to treat acid reflux and other conditions, there has been concern that reduced stomach acid could lead to bacterial overgrowth. However, the guideline recommends against testing asymptomatic patients on PPIs, as the clinical significance of bacterial overgrowth in the absence of symptoms is unclear.
We suggest testing for methane using glucose or lactulose breath tests to diagnose the overgrowth of methane-producing organisms (IMO) in symptomatic patients with constipation (conditional recommendation, very low level of evidence).
Constipation is associated with elevated levels of breath methane and stool Methanobrevibacter smithii. Methanobrevibacter smithii appears to be the key methanogen responsible for breath methane production. Targeting methanogens may reduce methane production and improve constipation.
We suggest the use of antibiotics in symptomatic patients with SIBO to eradicate overgrowth and resolve symptoms (conditional recommendation, low level of evidence).
Antibiotics are the primary treatment for SIBO. The goal is to reduce the excessive bacterial population in the small intestine and alleviate symptoms. However, the guideline notes that treatment has been largely empirical and requires careful appraisal.
The guideline also outlines several key concepts that are important for understanding and managing SIBO:
Prevention of SIBO is critically important to avoid the need for repeated courses of antibiotics. The guideline emphasizes that treatment of the underlying cause represents the primary mode of prevention.
The mechanisms for maintaining small bowel ecological homeostasis include several protective factors:
When these protective mechanisms are disrupted, SIBO can develop. Identifying and addressing the underlying cause is essential for preventing recurrence.
It is important to understand the limitations of the current evidence on SIBO. The guideline authors note several key limitations:
These limitations highlight the need for continued research to improve diagnostic accuracy and treatment outcomes for patients with SIBO.
If you are experiencing persistent bloating, gas, abdominal pain, or changes in bowel habits, SIBO may be a contributing factor, especially if you have IBS, a motility disorder, or have had abdominal surgery. The guideline recommends discussing breath testing with your healthcare provider to determine if SIBO is present.
For patients with constipation and elevated methane levels, the term IMO (intestinal methanogen overgrowth) more accurately describes the condition, and treatment may need to target methanogens specifically.
Antibiotics remain the primary treatment for SIBO, but it is equally important to identify and address the underlying cause to prevent recurrence. Work with your healthcare provider to develop a comprehensive treatment plan that addresses both symptom relief and root cause management.
SIBO is a condition where excessive bacteria grow in the small intestine, causing gastrointestinal symptoms. The most common symptoms include abdominal pain, bloating, gas, distension, flatulence, and diarrhea, which occur in more than two-thirds of patients. Symptoms can also mimic other conditions like IBS.
SIBO is diagnosed using either breath testing for hydrogen and methane or small bowel aspiration with culture. Breath testing is noninvasive and measures gases produced by bacteria. Small bowel aspiration, done during endoscopy, is considered the gold standard. A bacterial count of ≥10³ CFU/mL in the aspirate is diagnostic.
SIBO refers to overgrowth of bacteria in the small intestine. IMO, or intestinal methanogen overgrowth, is a newer term for overgrowth of methane-producing organisms called archaea, which are not bacteria. Methane levels ≥10 ppm on breath testing indicate IMO, and it is often associated with constipation.
The guideline suggests breath testing for SIBO in patients with irritable bowel syndrome (IBS), suspected motility disorders, or after abdominal surgery if they have symptoms like pain, gas, bloating, or diarrhea. It recommends against testing asymptomatic patients on proton pump inhibitors.
Antibiotics are the primary treatment for SIBO to eradicate bacterial overgrowth and resolve symptoms. However, it is also important to identify and treat the underlying cause to prevent recurrence. The guideline notes that treatment has been largely empirical and lacks rigorous trial data.
Prevention focuses on treating the underlying cause, as this is the primary mode of prevention. Protective factors include gastric acid, pancreatic enzymes, bile acids, and small bowel motility. When these are disrupted, SIBO can develop, so addressing the root cause is key to avoiding recurrence.
Breath testing has variable sensitivity and specificity, ranging from 20% to 93% for sensitivity and 30% to 100% for specificity. The diagnostic agreement between small bowel aspirates and breath testing is only about 65%, meaning one test may not definitively diagnose SIBO, and additional testing may be needed.
Original Article Title: ACG Clinical Guideline- Small Intestinal Bacterial Overgrowth
Authors: Mark Pimentel, MD, FRCP(C), FACG; Richard J. Saad, MD, FACG; Millie D. Long, MD, MPH, FACG (GRADE Methodologist); and Satish S.C. Rao, MD, PhD, FRCP, FACG
Publication: The American Journal of Gastroenterology (2020); Volume 115, pages 165–178
DOI: https://doi.org/10.14309/ajg.0000000000000501
Published Online: January 8, 2020
Publisher: © 2020 by The American College of Gastroenterology
This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and should not replace professional medical advice. Always consult with your healthcare provider about diagnosis and treatment options.
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