Multi-Biomarker Exploration of SIBO: an observational study (MBES)

Principal Investigator: Laurie Menk Otto, ND, MPH

Student investigator: Diane Saunders

Small intestine bacterial overgrowth (SIBO) is a syndrome in which one or more bacterial species exceed normal population levels, or bacteria that are not normally present in the small intestine colonize in large numbers.

The clinical presentation of SIBO is diverse, and the most common symptoms include diarrhea, flatulence, abdominal bloating and pain. SIBO patients often have a limited diet due to multiple food sensitivities that exacerbate SIBO symptoms and may give rise to extra-intestinal symptoms.  Extra-intestinal symptoms, such as impaired cognition, headaches, skin rashes, and myalgias are common and maybe due intestinal permeability and/or food sensitivities. The true prevalence of SIBO in the general population has not been established, but SIBO has been associated with a number of common conditions including irritable bowel syndrome, celiac disease, lactose intolerance, restless leg syndrome, acne rosacea, hypochlorhydria, hypothyroidism, Crohns disease and systemic sclerosis.

The known causes of SIBO fall into 5 categories: gastric achlorhydria, anatomical abnormality of the small intestine leading to stagnation, small intestine hypomotility, gastrocolic or gastroenteric fistula, and other miscellaneous causes such as immune compromise, comorbid autoimmune conditions and neurological disease.

Recent research suggests that one possible cause of hypomotility is the presence of auto-antibodies to the protein vinculin, a component of the small intestine pacemaker cell, which is required for neuronal stimulus of motility in the small intestine. This is suggestive of SIBO having an autoimmune origin and supplies a hypothesis for why SIBO is associated with other autoimmune conditions.

The overgrowth of bacteria in the small intestine is prevented by small intestine motility, the effectiveness of the ileocecal valve, and pancreatic enzyme and gastric acid activity.  The known risk factors for SIBO include abdominal surgeries, hypothyroidism, lactose intolerance, gastroenteritis, diabetes, and long-term use of antacids, proton-pump inhibitors, antibiotics or opiate medications.


At present, SIBO is best understood as a syndrome. Patients with SIBO commonly present with a combination of gastrointestinal and nonspecific systemic symptoms that have failed to resolve with standard treatment, which leads to the suspicion of SIBO. There is currently no validated diagnostic test for the diagnosis of SIBO. Diagnosis of SIBO can be made by breath test for hydrogen or methane gas production every 20 minutes for three hours following the consumption of lactulose, a non-absorbable sugar.  Even though the breath test has a sensitivity of 60-90% and a specificity of 85%, it is still used most often because it is the least invasive and most reproducible method.  SIBO can be also diagnosed via aspiration and direct culture of jejunal content, though the limitations of cost, invasiveness and potential contamination of the culture by oropharyngeal bacteria during intubation limit its widespread use.  In addition, the overgrowth may be patchy and therefore missed by a single aspiration.  Reproducibility has been as low as 38% using this method in comparison to 92% for breath testing. While all current testing can identify the presence or absence of SIBO, no method identifies the individual contributing factors for the overgrowth in each patient and therefore, treatment cannot address the specific cause, which often results in incomplete symptom resolution and relapse.

Treatment Challenges

Treatment of SIBO is limited to antibiotic or herbal antimicrobial therapies that subdue the bacterial overgrowth. While antimicrobial therapy can be effective in eradicating the overgrowth, it does not address or treat  the specific underlying cause in each patient. Therefore, incomplete symptom resolution and relapsing SIBO diagnoses are common. This may be due to the fact that every patient is treated the same, even though the underlying causes that enabled bacterial overgrowth vary from patient to patient. While the lactulose breath test can detect the presence of bacterial overgrowth, it does not indicate what underlying conditions allowed the bacterial populations to expand out of proportion. Further understanding of the pathophysiology and comorbidities of SIBO is necessary to provide better treatment outcomes and prevent relapse.

Study Purpose

It is unknown whether gluten enteropathy, intestinal permeability, food sensitivities, or autoimmunity are common among individuals diagnosed with SIBO. This study will measure and evaluate biomarkers specific to these factors from both the SIBO positive and negative population, for comparison. Current testing for SIBO can only detect the presence or absence of SIBO and indicates nothing about the underlying factors for the presenting symptoms. Current treatment of SIBO only serves to eradicate the overgrowth but does nothing for the underlying cause.  The resulting data form this study may improve future testing, treatment and resolution of SIBO. The study will also evaluate how biomarkers correlate to participant diet, symptom severity, and previous history for known risk factors and associated diseases. This study is the first to investigate the relationship between three potentially contributing factors (sensitivity to wide array of foods, gastrointestinal permeability, autoimmune conditions) and SIBO.