SIBO – SEATTLE, WA
What is SIBO?
Normal, healthy gut microbes (bacteria and archaea) are found in both small intestine and colon. However, the concentration of these microbes in the colon is much higher (about 100,000 times higher) than in the small intestine. Also, the type of bacteria found in the small intestine differs from that found in the colon. SIBO (small intestinal bacterial overgrowth) is a general term that describes a condition in which abnormally high numbers of bacteria and/or archaea are found in the small intestine.
The terminology associated with SIBO has been evolving over the last few years. Today, small intestinal bacterial overgrowth, abbreviated SIBO, is most often used to refer to an overgrowth of bacteria producing the gases hydrogen or hydrogen sulfide in the small intestine. Because archaea exclusively produce methane and are not bacteria, an overgrowth of methane-producing archaea is referred to as intestinal methanogen overgrowth, abbreviated IMO.
There are three types of gases produced by the organisms that cause SIBO/IMO:
- Hydrogen is most common and appears in ~80% of SIBO cases. Hydrogen is produced by bacteria including Enterobacter species, E. coli, and Klebsiella pneumoniae.
- Methane is observed in ~15% of SIBO cases and is produced by archaea (also called methanogens) primarily from the genus of Methanobrevibacter.
- Hydrogen-sulfide (H2S) is the least common gas and is observed in 5% or fewer cases of SIBO. It is produced bacteria including Desulfovibrio piger and Fusobacterium varium.
Individuals with small intestinal bacterial overgrowth can experience a range of gastrointestinal symptoms that may include gas and bloating, flatus, diarrhea (including steatorrhea), constipation, abdominal pain and discomfort, nausea and vomiting, nutrient malabsorption, fatigue, and in severe cases, malnutrition and weight loss. Patients with prolonged, untreated SIBO may display a variety of nutrient deficiencies secondary to malabsorption. These include anemias, especially microcytic anemia, which results from the inability to absorb iron, vitamin B12, and other nutrients essential for erythropoiesis.
RISK FACTORS FOR SIBO
Risk factors for the development of SIBO include disorders of gastrointestinal motility, disorders of the immune system, and conditions that lead to bacterial reflux from the colon into the small intestine. Alterations in gastrointestinal motility can result from diseases such as celiac disease or scleroderma that cause a general and widespread attenuation of peristalsis and an increase bacterial concentration in the small bowel. Diverticulitis is also frequently associated with SIBO as it causes small pockets in the small intestine where bacteria can collect and proliferate. Anatomical aberrations that may occur after resection of the gastrointestinal tract can also create regions of stasis where bacteria can collect. Pancreatitis, use/overuse of immunosuppressants, and genetic immunodeficiencies have been associated with SIBO. Surgical removal of the ileocecal valve can allow bacteria from the large bowel to inappropriately reflux into the ileum, and promote distal SIBO. Finally, the use of proton pump inhibitors, frequently used to prevent acid reflux, has been linked to the development of small intestinal bacterial overgrowth.
What CAUSES SIBO?
The smooth muscle of the gastrointestinal tract contracts and relaxes during digestion to move food from the stomach through the small intestine and to the colon (this process is known as peristalsis). This also helps move the bacteria from the small intestine into the colon, preventing them from multiplying to inappropriate levels. If the transport of food and bacteria in the small intestine is hindered, this can allow bacterial overgrowth in the small intestine and colonic bacteria to proliferate into the small intestine. Because peristalsis is controlled by the nervous system, muscular and neurological disorders can impact the function of the smooth muscles in the small intestine and lead to SIBO.
Diabetes, which can cause damage to gastrointestinal nerves, and scleroderma, which damages the muscles of the gastrointestinal tract, can both lead to SIBO. Partial obstruction of the small intestine can lead to SIBO as in the case of adhesions or scarring that occur as a result of surgery or as a result of Crohn’s disease or celiac disease. SIBO can also be caused by diverticulitis, in which the formation of small pouches in the small intestine which allow bacteria to proliferate. Additionally, decreased gastric acid secretion or the use of antacids, especially proton pump inhibitors (PPIs), can also contribute to the development of SIBO.
SYMPTOMS OF SIBO
Common symptoms of SIBO include:
- Bloating or abdominal distention
- Excessive gas or flatulence
- Abdominal pain
In severe cases, the overgrowth of bacteria can inhibit the absorption of nutrients and result in weight loss as well as vitamin and mineral deficiencies, such as iron deficiency anemia. Patients with SIBO may also experience symptoms such as fatigue or malaise. SIBO symptoms are often chronic, and patients often report that symptoms fluctuate in severity over a prolonged periods, sometimes months or years before ever being diagnosed with SIBO.
HOW IS SIBO DIAGNOSED?
SIBO is diagnosed primarily by one of two methods: (1) collecting and culturing bacteria from the small intestine, and (2) hydrogen and methane breath test.
ENDOSCOPY AND BACTERIAL CULTURE
This somewhat invasive method involves passing a tube through the nose and down through the throat, esophagus, and stomach to reach the small intestine. X-ray is used to guide the sample collection. From the sample, the number of live bacteria are cultured and quantified. There, however, are several disadvantages of this method when compared to hydrogen breath testing. First, obtaining a sample from the small intestine is invasive and uncomfortable for the patient and is an expensive medical procedure. Moreover, the training required to collect a suitable sample for culturing is not common among medical professionals. Because quantitative culturing of bacteria is not routine is most medical settings, the accuracy of the results are often questionable. Finally, a limited number of samples can be collected using this method, increasing the likelihood that a sample may be collected from a location that does not contain the bacterial overgrowth.
HYDROGEN AND METHANE BREATH TEST
Colonic microbes are capable of consuming carbohydrates as food to provide energy. When these microbes metabolize carbohydrates, they release the gases, carbon dioxide, hydrogen and methane, as waste products. The sorts of bacteria found in the small intestine, stomach, and esophagus produce very little gas. When we digest a meal, most of the carbohydrates are absorbed by the small intestine and never pass through to the colon. Additionally, more than 80% of the gas produced in the colon is consumed by other colonic microbes. And so, normally, little gas remains in the colon. Some of this gas passes from the colon into the bloodstream, eventually entering the lungs, where it is expired through normal respiration. The concentration of these gases in a patient’s breath can be measured using sophisticated instrumentation, such as a gas chromatograph. This method has the advantage of being relatively inexpensive, accurate, and useful in determining the location of the infection. You can read more about hydrogen and methane breath testing here.
TREATMENT FOR SIBO
Treatment of SIBO is typically begins after a positive breath test. The choice of a particular antibiotic regimen is influenced by the type of bacterial overgrowth as determined by the type of exhaled breath gases, potential contraindications such as antibiotic resistance or patient allergy, as well insurance coverage or cost of the antibiotic(s).
Generally, antibiotic therapy is as follows based on the exhaled breath gases detected:
- Hydrogen (SIBO): Rifaximin (Xifaxan®). The usual rifaximin regimen is 550 mg, 3 times per day typically prescribed as a 2-6 week course. A longer course of treatment may be needed to completely eradicate SIBO and reduce the risk of recurrence.
- Methane (IMO): The usual treatment regimen is rifaximin (550 mg, 3 times per day) for 2-6 weeks plus neomycin (500 mg, twice per day) or metronidazole (250 mg, 3 times per day) for for the first 14 days for treatment.
- Mixed hydrogen and methane (SIBO/IMO): The usual treatment regimen is rifaximin (550 mg, 3 times per day) for 2-6 weeks plus neomycin (500 mg, twice per day) or metronidazole (250 mg, 3 times per day) for for the first 14 days for treatment.
The pharmaceuticals used to treat hydrogen-predominant SIBO are normally rifaximin (550 mg, three times per day for 14 days with two more refills used in succession for a total of six weeks). If methanogens are also present, rifaximin is paired with neomycin or metronidazole for the first two weeks of treatment. Both rifaximin and neomycin are intraintestinal antibiotics and can be effective in treating SIBO with minimal side effects.
Clinical studies have also shown that herbal treatments can be effective as rifaximin in treating SIBO. Herbal treatments may be advantageous in some cases where rifaximin coverage is denied by the patient’s insurance carrier or is otherwise cost-prohibitive or unavailable, or where pharmaceuticals are contraindicated due to antibiotic resistance, side effect, or patient allergy.
The most researched products for treatment of SIBO is Candibactin-AR® and Candibactin-BR® from Metagenics. In a clinical study, combined use of Candibactin-AR® and Candibactin-BR® was as effective as rifaximin in treating SIBO when administered daily over four weeks. Both Candibactin-AR® and Candibactin-BR® are taken in combination for one month. Probiotics and fermentable foods are contraindicated when either herbal or pharmaceutical treatments are employed.
Herbal antibiotic therapies include:
- Candibactin-AR® and Candibactin-BR® from Metagenics
- FC-Cidal™ and Dysbiocide® from Biotics Research
In general, the herbal antibiotic therapy protocol is as follows based on the exhaled breath gases detected:
- Hydrogen (SIBO): Candibactin-AR® (1 capsule, 3 times per day) plus Candibactin-BR® (2 tablets, twice per day) for 6 weeks.
- Methane (IMO): Candibactin-AR® (1 capsule, 3 times per day) plus Candibactin-BR® (2 tablets, twice per day) plus Allimax® (1 capsule, 3 times per day) for 6 weeks.
- Mixed hydrogen and methane (SIBO/IMO): Candibactin-AR® (1 capsule, 3 times per day) plus Candibactin-BR® (2 tablets, twice per day) plus Allimax® (1 capsule, 3 times per day) for 6 weeks.
A combination of both pharmaceutical and herbal antibiotics can also be a viable treatment option, especially when indicated (e.g., emergent antibiotic resistance) or for practical reasons (e.g., medication cost or availability). Irrespective, of whether the treatment regimen is pharmaceutical or herbal, it is imperative to consider and assess clinical symptoms to determine when to cease treatment. For example, treatment too long with rifaximin can result in drier stool and constipation, therefore it is important to weigh symptom improvement vs. side effects throughout treatment. Lactulose or glucose breath test post-treatment can be used to determine if asymptomatic residual disease remains. It is always a good idea to ask your patients to provide an update of their symptoms every two weeks to monitor progress while on therapy.
JARISCH-HERXHEIMER REACTION (OR DIE-OFF REACTION)
The Jarisch-Herxheimer reaction (or just Herxheimer reaction), also known as a die-off reaction, refers to a temporary worsening of symptoms that can occur when gut bacteria are treated with antibiotics. When antibiotics are administered, they target and kill harmful bacteria in the gut, and may, as a side effect, also kill beneficial bacteria. Regardless, as bacteria die, they release toxins into the body, triggering an immune response. The sudden release of toxins can overwhelm the body’s detoxification systems, leading to symptoms such as fatigue, headache, muscle and joint pain, gastrointestinal distress, and flu-like symptoms. While uncomfortable, this die-off reaction is generally a sign that the treatment is working, as it indicates that bacteria are being eliminated from the body. It is important to support the body’s detoxification pathways during this period and to consult with a healthcare professional for guidance. Motility activating agents may be prescribed prior to, or concomitant with, initiation of antibiotic therapy to help minimize symptoms that may manifest as a result of a die-off reaction.
DIETARY MANAGEMENT OF SIBO
Dietary changes are not normally enough to treat SIBO, but dietary changes can be an important part of an herbal or pharmaceutical treatment regimen. FODMAP stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, which are the four classes of fermentable sugars and sugar alcohols. The Low FODMAP diet is one of three commonly prescribed diets when treating SIBO and is also prescribed to prevent SIBO recurrence. The low FODMAP diet eliminates the foods that contain the most fermentable carbohydrates within the intestines. The low FODMAP diet, however, does not restrict polysaccharide and disaccharide sources of carbohydrates that are poorly absorbed, so for some patients with SIBO, this diet can worsen the problem. If a patient doesn’t improve on the low FODMAP, the Specific Carbohydrate Diet (SCD) may be a viable alternative. SCD was first developed to treat celiac. It can also be effective for those patients during SIBO treatment who aren’t responding as well to the Low FODMAP. SCD limits complex carbs (disaccharides and polysaccharides), lactose and sucrose. These ingredients are harmful to the digestive system and lead to yeast overgrowth, bacterial overgrowth, and inflammation.
Although SIBO prevention strategies are still evolving, the following are steps that can be taken to prevent SIBO from occurring or recurring:
- Antibiotic Use: Antibiotics have been the primary treatment for SIBO, but their overuse can contribute to the development of antibiotic resistance. Research has explored alternative approaches, such as developing targeted antimicrobial agents to minimize the disruption of the gut microbiota.
- Probiotics and Prebiotics: Probiotics are live bacteria that can promote a healthy gut microbiota, while prebiotics are dietary fibers that nourish beneficial gut bacteria. Studies have investigated the potential of probiotics and prebiotics in preventing SIBO by maintaining a balanced gut microbiome. Some specific strains, such as Lactobacillus and Bifidobacterium species, have shown promise in inhibiting the growth of pathogenic bacteria associated with SIBO.
- Diet and Nutrition: Certain dietary modifications have been explored as potential prevention strategies for SIBO. Low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diets, which restrict specific carbohydrates that can ferment in the gut, have shown some effectiveness in reducing symptoms of SIBO. However, more research is needed to determine the long-term impact and optimal dietary approaches for prevention.
- Motility and Gut Transit: Impaired gut motility and slow transit can contribute to the development of SIBO. Researchers have investigated the use of prokinetic agents, which enhance gut motility and improve the clearance of bacteria from the small intestine, as a preventive measure for SIBO. Medications such as erythromycin and prucalopride have shown potential in enhancing gut transit and reducing bacterial overgrowth.
- Underlying Conditions: Identifying and managing underlying conditions that contribute to SIBO is crucial for prevention. Conditions like irritable bowel syndrome (IBS), celiac disease, and gastric surgery have been associated with an increased risk of SIBO. Research has aimed to improve the management of these conditions to reduce the likelihood of SIBO development.