Understanding SIBO: Pathophysiology, Diagnosis, and Interventions

Introduction: SIBO & Types of SIBO

SIBO is defined as a clinical syndrome of gastrointestinal (GI) symptoms caused by the presence of excessive numbers of bacteria in the small intestine, as defined based on small bowel aspirate/culture. The criteria to meet diagnosis are >/= 105 CFU/ml in the proximal jejunum or >/= 103 CFU/ml based on duodenal aspirates [1,2]. Symptoms of SIBO include diarrhea, gas, nausea, bloating, cramping, constipation, and/or abdominal pain and distension. Extreme cases may present with steatorrhea, weight loss, anemia, deficiencies in fat soluble vitamins, and/or inflammation of the small intestine mucosa[3].

While the current definition of SIBO focuses on the quantity of bacteria present in the small intestine, the types of organisms present plays a role in whether symptoms will be present. In the future, a more comprehensive definition of SIBO may also factor in the presence of dysbiosis, bacterial translocation, permeability, dysmotility and compromised immune function, along with a range of other clinical features [2].

SIBO may be hydrogen or hydrogen sulfide (H2S) predominant. In the past few years, methane predominant SIBO has been recognized as a distinct condition called Intestinal Methanogen Overgrowth (IMO) due to its different presentation features, such as presence of overgrowth in the colon. IMO is caused by methanogens, which are part of a different kingdom than bacteria, and symptoms are often dominated by constipation [3].

Prevalence of SIBO

Data on the prevalence of SIBO varies widely among studies and there is little consensus on the estimated SIBO rate. Among the healthy population alone, estimates on the prevalence of SIBO range from 0-20% (based on breath testing) [4]. Furthermore, the symptoms of SIBO overlap highly with other conditions, such as irritable bowel syndrome (IBS), further complicating diagnosis.

There is also high variability in prevalence within particular conditions, many of which may also be risk factors for SIBO themselves. These risk factors may be structural, biochemical or related to motility disturbances. For example, small bowel strictures and resections, diverticula and post-operative adhesions are structural abnormalities that may increase risk for SIBO. Biochemical risk factors may be related to low stomach acid or immunodeficiencies, while motility-related risk factors may include medications, such as opiates or anticholinergics, neurodegenerative conditions, like Parkinson’s disease, or poorly controlled diseases, such as diabetes [5].

These risk factors may also impact physiological mechanisms which protect against SIBO. Such mechanisms include gastric, pancreatic and biliary secretions, the innate immune system, the migrating motor complex and the ileocecal valve. Each of these serve distinct functions to prevent SIBO by helping protect against bacterial translocation from the colon to the small intestine and subsequent colonization there [6].

Pathophysiological Features

Pathophysiological effects of SIBO and the symptoms it can cause are wide-ranging. These may include mucosal injury, resulting in epithelial damage, loss of brush border enzymes, maldigestion, bacterial translocation and a range of inflammatory responses.

SIBO may also impact nutrient absorption due to competition by bacteria for luminal nutrients, such as protein, vitamin B12, thiamine, nicotinamide, as well as dietary protein. This may result in symptoms such as macronutrient or micronutrient deficiencies or weight loss [6].

SIBO can also lead to fermentation of dietary carbohydrates, bile acid deconjugation and increased synthesis of nutrients and byproducts, such as vitamin K, folate, D lactic acid, alcohol and acetaldehyde. This may lead to clinical symptoms such as bloating, flatulence, diarrhea and other features associated with bacterial metabolites [6].

Diagnosing SIBO

Current diagnostic methods include jejunal and duodenal aspirate, taken via endoscopy, as well as breath testing. The gold standard in diagnosis is by aspirate/culture at the time of endoscopy, though even this method lacks validation. Still, aspirate/culture can directly assess for SIBO and allows for identification of specific organisms present and any antibiotic sensitivities. Ideally, it is performed during work-up for other conditions, such as celiac disease, as it is expensive, invasive and time-consuming. Other drawbacks of aspiration include risk for contamination, procedural difficulties and that potential it may miss distal SIBO [7]. In practice, aspirate/culture is rarely performed and diagnosis via breath testing to assess for abnormal rises in hydrogen and methane is most common. Testing for elevated H2S levels can help assess for H2S predominant SIBO, but is less commonly performed.

Clinical guidelines recommend that symptomatic patients with IBS, constipation, suspected motility disorders and those who have had a previous abdominal surgery can be candidates for SIBO breath testing. Still, these are conditional recommendations with low levels of evidence [3]. Clinical judgment based on known risk factors for SIBO should also be incorporated into the decision to test for SIBO.

Lactulose and glucose breath tests are available and used in practice. Both are not always sensitive in identifying those who are truly positive (ie. avoiding false negative results). They also vary in their specificity in ruling out those without SIBO (ie. avoiding false positive results). Data suggest high rates of false positivity among both tests, so breath test results must be interpreted as part of a larger clinical picture. Patients may present with consistently positive results but experience symptom improvement, all of which should be considered in a treatment plan [1].

 In the future, portable at home breath tests may be able to support accurate and differential diagnosis. Gas capturing and gas sensing capsules also show potential to enable greater insight into the types of gasses and their amounts present, which currently poses challenges in clinical practice [6,7].

Treatment Options

            Treatment options for SIBO include medication and lifestyle interventions, though the level of evidence for all is often low. The vast majority of studies on SIBO interventions are small and many have methodological flaws, such as varying diagnosis criteria and methods of assessing symptoms [3]. Many questions remain on the role of diet and nutrition, supplements and lifestyle changes in SIBO treatment and symptom management.

            Meal spacing is sometimes recommended as a way to promote digestive cleaning waves, though data to support its efficacy is highly limited. The theory behind meal spacing is that it supports the housekeeping waves, also called the cleansing waves, of the migrating motor complex (MMC). These occur 90 minutes after a meal and help move food through the digestive tract, reducing food's availability for bacterial fermentation. When bacterial growth is elevated, such as with SIBO, these cleaning waves are reduced [8]. However, a small body of research shows that even after patients with SIBO fast for 4-5 these waves are still reduced, questioning whether meal spacing can in fact increase MMC activity [9].

Dietary Interventions for SIBO

A small body of research has evaluated various diets in SIBO treatment, including low FODMAP and low fermentation diets. Interpretation of findings is complicated by confounding factors, such as changes in motility related to dietary change, and there is no evidence for their use in treatment of SIBO.

However, there is preliminary evidence to suggest a low FODMAP diet may improve SIBO symptoms related to carbohydrate intolerance or IBS-related symptoms [10,11]. The low FODMAP diet can reduce gas, bloating and abdominal pain by reducing fermentable carbohydrates, but there is no research evaluating its efficacy as a treatment intervention in SIBO. Given the high overlap in SIBO and IBS, the low FODMAP diet may ultimately provide more benefits for IBS-related symptoms than for SIBO-related symptoms, though the presentation of both are highly overlapping [12].

The low fermentation diet restricts fermentable carbohydrates, like whole grains, lactose, fruits, cruciferous and several other vegetables, sweets and artificial sweeteners, beans and legumes and recommends meals be spaced 4-5 hours apart. It limits all fiber, regardless of type. There is no research to date on its efficacy for SIBO treatment or symptoms management and its highly restrictive nature poses significant risk for patients [9].

Conclusion & Further Learning

While there are no standardized evidence-based nutrition recommendations for SIBO, always aim to recommend the most liberalized diet possible to that helps restore microbiome health and manage symptoms. Emphasize with patients that research in this field is ongoing and there is no one-size-fits-all approach known to treat or manage SIBO.

Learn more about the role of diet, supplements and other lifestyle modifications in our recent free webinar with expert GI dietitian, Nancee Jaffe, MS, RDN, SIBO: Evidence and Nutrition Interventions. Nancee reviews the current evidence and research gaps for a range of interventions, including fiber, probiotics, Atrantil, berberine, peppermint, vitamin and mineral supplements and other herbal formulas. She also covers research on meal spacing and various diets for SIBO in further depth. The webinar provides a thorough update on current best practices and application of clinical recommendations in patients with SIBO. Watch here.