15% of the United States population has irritable bowel syndrome (IBS). Studies indicate up to 80% of people with IBS have small intestinal bacterial overgrowth (SIBO). Doing the math, this means that at least 39 million people have SIBO, and this doesn't account for patients who might have SIBO who have not been given an IBS diagnosis.
SIBO is associated with many disorders as both a cause and an effect of coexisting conditions. This article will discuss SIBO and some of its associated diseases that warrant SIBO testing when implementing a functional medicine approach to treatment.
What is Small Intestinal Bacterial Overgrowth (SIBO)?
SIBO is the overgrowth of bacteria that usually colonizes the colon within the small intestine. In a healthy state, bacteria pass through the small intestine, but innate mechanisms prevent bacteria from over-populating the small intestinal environment. When these mechanisms fail, bacteria can overgrow within the small intestine, causing small intestinal inflammation and resulting in leaky gut, maldigestion, and associated symptoms. (1)
Three distinct variants of SIBO have been determined, based on breath test findings and the predominance of gas types produced in the gastrointestinal tract by microorganisms. Hydrogen-SIBO is the overgrowth of hydrogen-producing bacteria within the small intestine. Hydrogen sulfide-SIBO is the overgrowth of hydrogen sulfide-producing bacteria in the small intestine. Intestinal methanogen overgrowth (IMO) is the overgrowth of archaea (bacteria-like organisms) within the small or large intestines. (1)
The most common symptoms related to SIBO are gastrointestinal symptoms, very similar to IBS symptoms (2, 3). A patient may experience some, all, or none of these:
- Abdominal pain
- Abdominal distension and bloating
- Diarrhea: associated with hydrogen and hydrogen sulfide excess
- Constipation: associated with methane excess
Malabsorption caused by SIBO may cause unintentional weight loss, fatigue, and fatty stools. Iron and vitamins B1, B3, B12, and D commonly become depleted due to maldigestion and bacterial overutilization. (2)
Leaky gut, and the resulting overstimulation of pro-inflammatory immune responses, may predispose a patient to experience symptoms outside of the digestive tract, including (1):
- Joint pain
- Brain fog
- Skin symptoms: eczema, rosacea, psoriasis, and other rashes
- Changes in mood: depression and anxiety
What Causes SIBO?
Innate protective defenses against bacterial overgrowth within the small intestine include digestive enzymes (stomach acid, proteolytic enzymes, bile), peristalsis (waves of intestinal muscle contractions that propel intestinal contents forward), an intact ileocecal valve, and secretory IgA (sIgA). Digestive enzymes kill and prevent bacteria passing through the stomach and small intestines after ingesting food. The migrating motor complex (MMC) is responsible for peristalsis and the cleansing of the small intestine during a fasting state. The ileocecal valve acts as the junction and barrier between the small and large intestines to prevent the backward migration of bacteria from the colon into the small intestine. sIgA plays a role in the first line of defense in protecting the intestinal mucosa from pathogens and toxins. (2)
The etiology of SIBO is complex and multifactorial. Imbalances, dysfunction, and abnormalities in motility, immune function, digestive enzymes, and anatomy can contribute to the development of SIBO.
Risk Factors for Developing SIBO
Age, medical conditions, surgical procedures, and medications can interrupt the normal protective barriers against SIBO, increasing your risk of developing the disease.
Advanced age is associated with lower stomach acid and motility (3).
Abdominal surgery and radiation therapy can damage the mucosal lining, negatively affecting mucosal immunity, and contribute to the formation of strictures and adhesions within the small intestine, contributing to dysmotility (3).
Medical conditions can reduce mucosal immune response, slow intestinal motility, and create intestinal structural problems. These may include:
- Diabetes mellitus
- Autoimmune diseases: lupus, celiac disease, inflammatory bowel disease (IBD), scleroderma
- Digestive enzyme deficiencies caused by low stomach acid (hypochlorhydria), pancreatitis, gallbladder disease, liver disease, and exocrine pancreatic insufficiency (EPI)
- Colon cancer
The use of certain medications can also increase SIBO risk. Antibiotics can slow intestinal motility and disrupt the healthy balance of the intestinal microbiome (3). Opiates and smooth muscle relaxants can contribute to dysmotility. Proton pump inhibitors (PPIs) and other acid-reducing medications cause hypochlorhydria.
5 Medical Conditions Associated with SIBO
SIBO is a confounding factor in the development and progression of many intestinal and extra-intestinal disorders. Below are some conditions in which SIBO should be considered as part of the etiology of disease onset and development.
Numerous studies support the pathogenic role of SIBO in the development and severity of rosacea, an inflammatory skin condition associated with facial flushing. Alteration of immune responses and the augmentation of inflammation and pro-inflammatory cytokines caused by SIBO likely contribute to disease development, especially papulopustular rosacea. According to one study, patients with rosacea are 13 times more likely to have SIBO than those without, and eradicating SIBO with the antibiotic rifaximin leads to almost complete regression of rosacea lesions for three years. (6)
Restless Legs Syndrome (RLS)
RLS is a neurological sensory and sleep disorder characterized by aching, throbbing, and creeping sensations in the legs that create an overwhelming desire to move the lower extremities.
A 2021 systematic review with meta-analysis found a bidirectional association between IBS and RLS; patients with IBS have a threefold increased risk of RLS, and patients with RLS have a fourfold increased risk of IBS. Evidence also supports the association between SIBO, IBS, and RLS, and perhaps more importantly, has shown long-term improvement in RLS when SIBO treatment is administered to patients. Hypotheses regarding the correlation between SIBO, IBS, and RLS include: immunocompromise in RLS predisposes to SIBO; autoimmunity induced by SIBO leads to changes in the nervous system and sensory perception; and SIBO-associated iron deficiency leads to RLS.
Interstitial Cystitis (IC)
IC, also called Bladder Pain Syndrome, is a poorly understood chronic pain syndrome that affects the bladder and pelvic area.
In a 12-year cohort study, IBS was shown to increase the risk of developing IC. Most patients with IC and concurrent gastrointestinal symptoms also test positive for SIBO. Nearly half of the patients treated with antibiotic and prokinetic therapy experience substantial improvement in IC symptoms. (7)
Patients with hydrogen sulfide-SIBO may be at higher risk for developing IC, as hydrogen sulfide is a known inflammatory mediator shown to facilitate bladder pain.
Patients with diabetes mellitus (type 1 and type 2) have nearly three times more risk of SIBO than those without. It is estimated that 29% of patients with diabetes have SIBO. Diabetic neuropathy, nerve damage caused by elevated blood sugar, and gastroparesis, the slowing of stomach emptying, are two common complications of diabetes that increase the risk of SIBO (8, 9). Conversely, SIBO may also lead to worse health outcomes and poorer glucose control in patients with diabetes, including slowed intestinal transit, malabsorption, worse glycemic control, and higher insulin requirements (8, 10, 11).
Intestinal dysbiosis contributes to systemic inflammation and joint pain by activating the immune system. Patients with autoimmune arthritis, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS), have high rates of SIBO. Additionally, the presence of SIBO is associated with increased autoimmune disease activity.
Functional Medicine Labs to Diagnose SIBO
Hydrogen breath tests are the most commonly utilized diagnostic method for diagnosing SIBO, as they offer an inexpensive and noninvasive alternative to gold standard diagnosis by small intestinal culture (4).
SIBO breath tests can be performed by the patient at home following a low-fiber preparatory diet and 12-hour overnight fast. Patients collect a baseline breath sample by exhaling into a tube and then drink a glucose or lactulose solution. The patient continues to collect breath samples at timed intervals (usually every 15-20 minutes) for two or three hours.
Traditional SIBO breath tests measure hydrogen and methane gases. A positive SIBO breath test is interpreted as (5):
- Hydrogen levels increase by 20ppm within three hours from baseline
- Methane levels of at least 10ppm at any timepoint during the test
- Suppose the test does not meet positive criteria for hydrogen or methane levels. In that case, a combined hydrogen and methane level increase by at least 15ppm within three hours from baseline constitutes a positive test.
The trio-smart is the newest SIBO breath test on the market that measures all three gas types associated with SIBO: hydrogen, methane, and hydrogen sulfide. The same diagnostic criteria are used for interpreting hydrogen and methane levels. A hydrogen sulfide level of at least 3ppm at any timepoint during the test indicates a positive test.
Other Labs Used in the Evaluation of SIBO and Its Associated Conditions
Functional medicine labs help practitioners personalize treatment options for their patients. Below are some of the most common labs ordered for patients suffering from SIBO and associated medical conditions.
Comprehensive Stool Analysis
A comprehensive stool analysis helps diagnose dysbiotic patterns known to cause many of the diseases associated with SIBO. Additionally, stool testing can diagnose and quantify malabsorption, intestinal inflammation, and poor immune function by measuring fecal fats, bile acids, calprotectin, and sIgA.
The GI-MAP is a commonly ordered stool test by providers specifically interested in ruling out H. pylori infection, which has been studied as a possible causative factor of rosacea.
Nutrient imbalance patterns commonly seen with SIBO and other conditions can be measured and monitored with a comprehensive nutritional assessment. Common lab findings in SIBO include elevated folate and low iron, vitamin D, and B12. Iron and vitamin D deficiencies are also associated with RLS.
A comprehensive blood workup for diabetes and insulin resistance (a precursor to type 2 diabetes) includes a CBC, CMP, hemoglobin A1c (HbA1c), insulin, and a lipid panel.
Hypothyroidism can slow gut motility. Hypothyroid and hyperthyroid states have been associated with RLS. A comprehensive thyroid panel measures hormones in the thyroid cascade to diagnose thyroid dysfunction.
The Cyrex Array 5 is a multiple autoimmune reactivity screening panel that can determine potential tissue damage in various body organs and tissues. Measuring autoantibodies associated with SLE, inflammatory bowel disease, and type 1 diabetes (among others) can predict and aid in diagnosing autoimmune disease development as it pertains to SIBO.
Slowed gastrointestinal activity may also be caused by autoimmunity within the small intestine triggered by acute intestinal infections (i.e., food poisoning, traveler's diarrhea). Antibodies associated with post-infectious IBS and SIBO can be measured to confirm pathogen-induced dysmotility.
Antroduodenal manometry, endoscopy, and barium follow-through can be ordered to diagnose MMC deficiency and structural anomalies causing SIBO and IMO.
A Functional Medicine Approach to Treating SIBO and Its Associated Conditions
SIBO eradication with antibacterial therapy not only improves gastrointestinal symptoms but may also be a critical aspect of addressing the underlying causes of RLS, IC, autoimmune disease, rosacea, and diabetes.
Antibiotic and herbal antimicrobials are shown to be equally effective in eradicating SIBO.
Antibiotic therapy is dosed for a minimum of two weeks. Rifaximin is sufficient in treating hydrogen-SIBO, but it is usually paired with neomycin or metronidazole to treat IMO or bismuth to treat hydrogen sulfide-SIBO. (1)
Herbal therapy is most effective when two antimicrobial herbs are dosed together for at least four weeks. Oregano, berberine, and neem are effective in the treatment of hydrogen-SIBO. Adding allicin to one of the above herbs appears more beneficial in treating IMO. (1)
The elemental diet (ED) is the most extreme, but most effective, option for treating SIBO. An ED formula consists of pre-digested nutrients that nourish the patient while starving microorganisms in the gut.
SIBO recurrence is estimated to be as high as 43.7% within nine months after the cessation of antibiotic therapy without adding preventive measures to the treatment plan. SIBO prevention should always include a prokinetic agent, such as ginger, which enhances the MMC, small intestinal motility, and gastric emptying to prevent the accumulation of bacteria in the small intestine. Other preventive strategies include managing underlying diseases interfering with intestinal defense mechanisms, digestive enzymes, and stress management. (1)
Nutrition for SIBO and Its Associated Conditions
Therapeutic elimination diets can remove triggers exacerbating SIBO symptoms, intestinal permeability, and inflammation.
The low-FODMAP diet is one of the most popular therapeutic diets for managing SIBO and IBS symptoms. It functions to limit highly-fermentable carbohydrates that "feed" the bacteria in the small intestine. Treatment goals should include successfully reincorporating FODMAP foods into the diet once SIBO eradication is achieved.
Once SIBO is eradicated, a whole-food, anti-inflammatory diet is recommended to support a healthy gut microbiome, stabilize blood sugar, reduce systemic inflammation, and prevent nutritional deficiencies. The Mediterranean diet is one such diet backed by research to be beneficial in treating many medical conditions and preserving and optimizing general well-being.
SIBO breath testing is an important aspect of diagnosing SIBO that causes gastrointestinal symptoms and identifying SIBO as a causative factor of other health conditions that may appear unrelated to the gut. A plethora of evidence supports the bidirectional relationship between SIBO and other health conditions. Health conditions interrupting innate defense mechanisms against bacterial overgrowth can contribute to SIBO development, but SIBO can also induce systemic imbalances, leading to extraintestinal symptoms and diseases. Functional medicine providers utilize functional testing to uncover the root causes of illness. Test results help to personalize holistic treatment recommendations that target root causes of dis-ease and optimize whole-body health and wellbeing.
Lab Tests in This Article
1. Cloyd, J. (2023, March 30). An In-Depth Overview of the Three Types of SIBO: Hydrogen, Methane, Hydrogen Sulfide. Rupa Health. https://www.rupahealth.com/post/an-in-depth-overview-of-the-three-types-of-sibo-hydrogen-methane-hydrogen-sulfide
2. Sorathia, S.J,, Chippa, V., & Rivas, J.M. (2022). Small Intestinal Bacterial Overgrowth. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK546634/
3. SIBO (Small Intestinal Bacterial Overgrowth): Symptoms, Diet, Causes & What it Is. (n.d.-c). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/21820-small-intestinal-bacterial-overgrowth-sibo
4. Sachdev, A.H., & Pimentel, M. (2013). Gastrointestinal bacterial overgrowth: pathogenesis and clinical significance. Therapeutic Advances in Chronic Disease, 4(5), 223–231. https://doi.org/10.1177/2040622313496126
5. Greenan, S. (2021, November 2). Constant Burping Is A Sign Of This Harmful Bacterial Overgrowth. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-approach-to-sibo
6. Daou, H., Paradiso, M., Hennessy, K., & Seminario-Vidal, L. (2021). Rosacea and the Microbiome: A Systematic Review. Dermatology and Therapy, 11(1), 1–12. https://doi.org/10.1007/s13555-020-00460-1
7. Weinstock, L.B., Klutke, C.G., & Lin, H. (2008). Small Intestinal Bacterial Overgrowth in Patients with Interstitial Cystitis and Gastrointestinal Symptoms. Digestive Diseases and Sciences, 53(5), 1246–1251. https://doi.org/10.1007/s10620-007-0022-z
8. Ojetti, V., Pitocco, D., Scarpellini, E., et al. (2009d). Small bowel bacterial overgrowth and type 1 diabetes. European Review for Medical and Pharmacological Sciences, 13(6), 419–423.
9. Reddymasu, S., & McCallum, R.W. (2010). Small Intestinal Bacterial Overgrowth in Gastroparesis. Journal of Clinical Gastroenterology, 44(1), e8–e13. https://doi.org/10.1097/mcg.0b013e3181aec746
10. Cuoco, L., Montalto, M., Jorizzo, R.A., et al. (2002). Eradication of small intestinal bacterial overgrowth and oro-cecal transit in diabetics. Hepato-Gastroenterology, 49(48), 1582–1586.
11. Yan, L., Mu, B., Pan, D., et al. (2020). Association between small intestinal bacterial overgrowth and beta-cell function of type 2 diabetes. Journal of International Medical Research, 48(7), 030006052093786. https://doi.org/10.1177/0300060520937866