In recent years, evidence has accumulated that bacterial overgrowth in the small intestine, coupled with impaired motility, frequently underlies the condition that has long been described as irritable bowel syndrome (IBS). Small intestine bacterial overgrowth (SIBO) is easily diagnosed with hydrogen breath testing, and effectively treated with antimicrobials, prokinetics, and dietary avoidance of fermentable carbohydrates. Practitioners treating SIBO come to understand that it usually is a chronic, relapsing condition that demands multiple courses of treatment and attention to underlying contributory factors in order to achieve durable remission. Others question whether the condition actually exists. This brief article will address the history of SIBO, diagnostic criteria, testing, risk factors, and treatment strategies.
IBS is characterized by abdominal pain, diarrhea, constipation (or both), bloating, and flatulence. It occurs in 10-20% of the population in North America, and is the most frequent disorder diagnosed by gastroenterologists. Some consider it the most common chronic medical condition.
SIBO is an accumulation of bacteria in the small intestine. The overgrowth is of bacteria that normally live in the gastrointestinal tract but have abnormally overgrown in a location not meant for so many bacteria. Up to 1 out of 7 persons in North America have SIBO. There are numerous problems with SIBO. The bacteria:
- interfere with normal digestion and absorption and damage the lining of the small intestine (“leaky gut syndrome,” or leaky small intestine in this case)
- consume some of our food which over time leads to deficiencies in their favorite nutrients (iron, B12) causing anemia or low ferritin
- consume food unable to be absorbed due to small intestinal lining damage, which continues the overgrowth (vicious cycle)
- produce gas within the small intestine, causing bloating, pain, constipation, diarrhea (or both), belching and flatulence; methane produces constipation; hydrogen produces diarrhea
- decrease proper fat absorption by de-conjugating bile, leading to deficiencies of vitamins A & D and fatty stools
- through damaged SI lining, larger food particles not able to be fully digested, enter into the blood causing food allergies/ sensitivities
- bacteria themselves can also enter the bloodstream; immunologic reactions to bacteria and their cell walls (endotoxins) can cause chronic fatigue and pain and burden the liver
- excrete acids which may, in high amounts lead to neurological and cognitive symptoms.
History of SIBO
In the 1970s, IBS was considered to be psychogenic, and was treated with antidepressant medication. In the 1980s, it was recognized to be a motility disorder, with two subtypes: IBS-C (constipation) and IBS-D (diarrhea). Researchers developed the “Rome criteria.” It was not intended to be used for clinical diagnosis. The condition was treated with serotonin reuptake-antagonists and agonists. In the 1990s, altered pain perception in the GI tract was observed in IBS, known as “visceral hypersensitivity.” And the syndrome of “post-infectious IBS” was described, in patients who developed IBS following an episode of food-borne illness. In 2006, Mark Pimentel’s book “A New IBS Solution” was published, wherein he reported his findings that bacteria were the missing link in treating IBS. In 2011, Allison Siebecker, ND, MSOM, LAc began writing and lecturing on SIBO and brought awareness of the condition to the naturopathic profession. In 2015, the antibiotic rifaximin was approved for the treatment of IBS-D, and it became the standard conventional treatment for SIBO.
Diagnostic Criteria
Unfortunately, there is no perfect test. The small intestine (SI) is a hard place to gain access. If we want to see or sample the SI, endoscopy only reaches into the top portion, and colonoscopy only reaches into the end portion. The middle portion, which is substantial (approximately 17 feet), is not accessible, other than by surgery. And stool testing predominantly reflects the large intestine. Luckily, there is a non-invasive test which is commonly used in SIBO research and clinical practice: the Hydrogen Breath Test.
Testing
The Hydrogen Breath Test is used to diagnose several conditions: H. pylori infection, carbohydrate malabsorption (e.g. lactose) and SIBO. The SIBO Breath Test measures the hydrogen (H) & methane (M) gas produced by bacteria in the SI that has diffused into the blood, then lungs, for expiration. H & M are gases produced by bacteria, not by humans. The gas production is graphed over the SI transit time of 2 or 3 hours and compared to baseline. Patients drink a sugar solution of glucose or lactulose after a one-day preparatory diet. The diet removes much of the food that would feed the bacteria, allowing for a clear reaction to the sugar solution.
Lactulose Breath Test (LBT) and Glucose Breath Test (GBT)
Humans cannot digest or absorb lactulose. Only bacteria have the proper enzymes to do this. After they consume lactulose, they make gas. If there is overgrowth, this will be reflected in levels of H and/or M. The advantage to LBT is that it can diagnose overgrowth in the distal end of the SI, thought to be more common. The disadvantage is that it cannot diagnose bacterial overgrowth as well as the GBT. Both humans and bacteria absorb glucose. Glucose is absorbed within the first three feet of the SI. Therefore, if the bacterial gases of H and/or M are produced during this test, it reflects an overgrowth in the proximal/upper end of the SI (within the first two feet). The advantage to this test is that it successfully and accurately diagnoses proximal overgrowth. The disadvantage is that it cannot diagnose distal overgrowth, occurring in the latter 17 feet of the SI, which is thought to be more common.
The tests are typically performed at home with a take home kit. It takes 3 hours in the morning after a 12 hour fast the night before and a special diet the day before. At home kits may be obtained from numerous breath testing laboratories. Lactulose kits require a physician prescription.
In 2017 the North American Consensus statement was published on H and M-based breath testing. A rise in hydrogen of ≥20 ppm by 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥10 ppm was considered methane-positive.
Risk Factors
Some people are more predisposed to the development of bacterial overgrowth because of certain risk factors. These factors can be grouped into three categories: (1) disordered motility or movement of the small bowel or anatomical changes that lead to stasis, (2) disorders in the immune system and (3) conditions that cause more bacteria from the colon to reflux into the small bowel.
Problems with motility may either be diffuse or localized to particular areas. Diseases like scleroderma and possibly celiac disease cause diffuse slowing of the bowel, leading to increased bacterial concentrations. More commonly, the small bowel may have anatomical problems, such as diverticula that can cause bacteria to accumulate. After surgery involving the stomach and duodenum (most commonly with Billroth II antrectomy), a blind loop may be formed, leading to stasis of flow of intestinal contents. This can cause bacterial overgrowth and is termed blind loop syndrome.
Disorders of the immune system can cause bacterial overgrowth. Chronic pancreatitis, or inflammation of the pancreas can cause bacterial overgrowth through mechanisms linked to this. The use of immunosuppressant medications to treat other conditions can cause SIBO. Other causes include inherited immunodeficiency conditions, such as common variable immunodeficiency, IgA deficiency, and hypogammaglobulinemia.
Finally, abnormal connections between the bacteria-rich colon and the small bowel can increase the bacterial load in the small bowel. Patients with Crohn’s disease or other diseases of the ileum may require surgery that removes the ileocecal valve connecting the small and large bowel; this leads to an increased reflux of bacteria into the small bowel. After bariatric surgery for obesity, connections between the stomach and the ileum can be formed, which may increase bacterial load in the small bowel.
Proton pump inhibitors, used to reduce stomach acid, are associated with an increased risk of developing SIBO.
Bacterial overgrowth can cause a variety of symptoms, many of which are also found in other conditions, making the diagnosis challenging at times. Many of the symptoms are due to malabsorption of nutrients due to the effects of bacteria which either metabolize nutrients or cause inflammation of the small bowel, impairing absorption. This is why SIBO can lead to fatigue and weakness. Some patients may lose weight. Children with bacterial overgrowth may develop malnutrition and have difficulty attaining proper growth.
Anemia may occur from a variety of mechanisms, as many of the nutrients involved in production of red blood cells are absorbed in the small bowel. Iron is absorbed in the duodenum and jejunum, and patients with malabsorption of iron can develop microcytic anemia. Vitamin B12 is absorbed in the ileum, and patients who malabsorb vitamin B12 can develop megaloblastic anemia. In older adults, SIBO is associated with a higher frequency of diarrhea, a lower body mass index, and a significantly lower serum albumin concentration.
Food poisoning, otherwise known as food-borne illness or infectious gastroenteritis, is a very common antecedent to SIBO. Not only are pathogenic bacteria introduced to the SI, but they produce cytolethal distending toxin B. Anti-Cdt-b antibodies cross-react with vinculin, a protein that connects the interstitial cells of cajal (ICC) of small intestine lining leading to abnormal motility and an autoimmune state. Myenteric ICC serve as a pacemaker which creates the bioelectrical slow wave potential that leads to contraction of intestinal smooth muscle. This is termed the migrating motor complex (MMC). A blood test known as IBScheck looks for antibodies to Cdt-b and vinculin to aid in the diagnosis of IBS and SIBO.
SIBO is common in rheumatoid arthritis and other rheumatic conditions, inflammatory bowel disease, liver disease, rosacea, systemic sclerosis, Ehlers Danlos Syndrome, asthma, vaso-reactivity, and histamine sensitivity. Digestive symptoms need not be present. Additional risk factors for SIBO include: high carbohydrate diet, frequent antibiotic treatment, hypochlorhydria (PPI use), opiate use, alcohol abuse, hyoscyamine, anticholinergics, antispasmodics, conditions leading to adhesions (abdominal and pelvic surgery, endometriosis, abdominal trauma), traumatic brain injury, obesity, and gastroparesis.
Treatment
Three essential elements comprise effective treatment for SIBO: eliminate the bacteria, restore motility, and restoration of the intestinal lining. Bacteria can be eliminated with rifaximin and other prescription antibiotics, herbal antibiotics, elemental diet, and low FODMAP diet. As emphasized above, most patients require multiple courses of various treatments to achieve long-lasting remission.
Prescription Antibiotics
Dose finding studies of prescription antibiotics have achieved up to 91% success in eradicating SIBO (measured by hydrogen breath test) and 94% symptom improvement. The primary antibiotics used are rifaximin (Xifaxan) and neomycin. Both are almost completely non-absorbable and do not usually cause systemic side effects, such as urinary tract or yeast infections. Rifaximin is expensive in the US ($400-$1000 for 14 days). Metronidazole can also be used as an alternative to neomycin. Rifaximin may be used for all cases of SIBO. Dose is 550 mg 3 times daily for 14 days. For IBS-C, combination therapy with rifaximin and neomycin (500 mg twice daily) or metronidazole (250 mg 3 times daily) is recommended. If alternating diarrhea is present with constipation, the use of rifaximin alone is suggested.
Herbal Antibiotics
Herbal antibiotics are as effective as pharmaceutical antibiotics in relieving symptoms and reducing gas levels on breath testing. A multi-center study found “herbal therapies are at least as effective as rifaximin” with “similar response rates and safety profiles.” The study used two herbal combination formulas together, at a dose of 2 caps 2 x day x 4 weeks, for each formula. I will typically prescribe two of the following herbs for 4 – 8 weeks: Allicin SAP 1 capsule twice daily; Oregano oil SAP (titrate gradually from 2 drops twice up to tolerance); Berberine SAP (2 capsules twice daily), Neem SAP (2 capsules twice daily). Allicin is the highest potency allicin available (1% allicin).
Elemental Diet
This approach seeks to starve the bacteria, but feed the person, by replacing meals for two weeks with an elemental formula: powdered nutrients in pre-digested, easily absorbed form. Elemental formulas contain amino acids, carbohydrate as glucose and/or maltodextrin, fat as various oils, and vitamins & minerals. Advantages of the elemental diet are safety and an 80-84% success rate in eradicating SIBO. Drawbacks are expense, no eating for 2 weeks treatment, and weight loss if sufficient calories (1800-2000) are not consumed.
Therapeutic Diets
All dietary treatments strive to reduce the food sources for the bacteria. They seek to feed the person but starve the bacteria. Diet has a significant impact on our intestinal bacterial population. Bacteria primarily use carbohydrates for their growth so all the recommended diets decrease carbohydrates to reduce the bacteria by limiting their preferred substrate. The only carbohydrate that bacteria do not utilize for their growth is insoluble fiber.
The established SIBO treatment diets are the Specific Carbohydrate Diet (SCD), the Gut and Psychology Syndrome Diet (Gaps Diet), the Low Fodmap Diet (LFD) or a combination of these diets such as SCD + LFD. FODMAP is the acronym for Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols. Dr. Siebecker’s version of a combination of SCD + FODMAP combines the best of both diets, reducing a broader range of fermentable carbohydrates than any other SIBO diet. The SIBO Specific Food Guide (SSFG) App, developed by Dr. Siebecker is a reference food guide and contains only minimal usage instructions. A variation of the SSFG by SIBO specialist Nirala Jacobi ND is called the SIBO Bi-Phasic Diet (https://www.thesibodoctor.com/product/sibo-bi-phasic-diet/?v=7516fd43adaa). Several excellent cookbooks based on the Bi-Phasic Diet are available at: http://www.breathtests.com/patientstore.html
Prior to starting the SIBO diet, the patient should be asked what foods they want to be able to eat, and what foods they may miss. It’s possible that the diet can allow exceptions to the SIBO diet guidelines to accommodate desire for some of patient’s favorite foods. Any dietary guidelines should incorporate the principle that any food that aggravates symptoms should be avoided, and any food that is tolerated may be permitted.
Some carbohydrates are absorbed so quickly in the gut they may not have time to be fermented. These are the single sugars glucose and fructose, which exist on their own in honey but are combined with fermentable carbohydrates in all other foods. Ripe fruit, non-starchy vegetables and nuts are allowed on the diets for health and variety purposes, even though they do contain fermentable carbohydrates.
Diet alone may provide enough symptom relief that no other treatment is desired. However, if malabsorption or leaky gut is present, other treatment is advised to allow the damaged SI lining to heal after antibiotics. See the section below on restoration.
Prokinetics
A prokinetic to address the underlying dysfunctional motility is prescribed immediately after following the first course of treatment (prescription antibiotic, herbal antibiotics, or elemental diet). Tolerance develops after a few weeks, it is advisable to rotate through all these prokinetics. A trial removal of the prokinetic after at least 3 months is suggested, but continued long-term use may be needed. Prokinetics studied for SIBO include the following pharmaceuticals and supplements:
Low-dose Naltrexone (LDN) – 2.5 mg for diarrhea types or 5 mg for constipation types, at bedtime. Low-dose Erythromycin – 50 mg at bedtime. Compounding necessary for this low dose, or quarter a 250 mg pill to get 62.5 mg. Contraindicated with berberine.
Prucalopride (Resolor/Resotran) 0.5-1 mg at bedtime (not available in the United States but available in Canada and some European countries; has not been specifically studied for SIBO) Compounded formulation: Pyridoxal 5′ phosphate, Ginger root, Acetyl-L-Carnitine, 5-hydroxytryptophan.
Ginger SAP 1 capsule 3 times daily
Compounded formulation: 20 drops 3 times daily (Bitter candytuft, Angelica; Chamomile; Caraway, St Mary’s thistle; Lemon Balm; Peppermint; Greater celandine; Licorice) Anxiety impairs gut motility. One or more forms of stress management should be part of the treatment plan: mindfulness training, mindfulness-based cognitive therapy, meditation, yoga. Patients should be counseled to not hurry and not worry.
Restoration
The intestinal lining may need time to repair from the damage of SIBO before it can properly digest and absorb all foods. A minimum of three months of supplementation with probiotics and a GI repair formula is recommended for this purpose. See recommended products below. Evidence for the benefit of probiotic therapy in patients with SIBO is controversial. Findings from a meta-analysis indicated probiotics supplementation could significantly decontaminate SIBO, decrease H2 concentration, and relieve abdominal pain, but were ineffective in preventing SIBO. SIBO is far too complex to support a claim that certain types of bacteria will solve the problem of SIBO when there is interplay between hundreds of different types of bacteria in the GI tract.
Recommended probiotics: Probio SAP, Bifido SAP 1 capsule daily. Recommended GI repair formula: NFH GI Repair SAP-Coming soon (Quercetin, Aloe vera, Marshmallow, Deglycyrrhizinated Licorice Root, L-glutamine, methylsulfonylmethane, N-acetylglucosamine, apple pectin, Slippery Elm, Cat’s Claw, Zinc L-carnosine, Ginger, Curcumin)
Commentary: Robust evidence confirms that SIBO is a laboratory finding of dysbiosis that underlies most cases of IBS. NFH offers a full line of products for the successful treatment of SIBO: Allicin SAP, Oregano SAP, Berberine SAP, Neem SAP, Ginger SAP, Probio SAP, Bifido SAP, and GI Repair SAP (coming soon).
References
- Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. Am J Gastroenterol. 2017;112(5):775-784
- Bures J et al. World J Gastroenterol. 2010 28;16(24):2978-90.
- Pimentel, M., et al. Clin Ther. 2016 Jul;38(7):1638-1652
- http://www.siboinfo.com/associated-diseases.html
- Chedid, V., et al. Global Adv Health Med.2014;3(3):16-24.
- Pimentel, et al. Dig Dis Sci. 2004;49(1):73-7.
- Ploesser, J., et al. Int J Pharm Compd. 2010;14(2):171-3.
- Pimentel, M., et al. Gastroenterol Hepatol. 2009;5(6):435-42.
- Zhong, C., et al. J Clin Gastroent. 2017;51(4):300-311
- Compare, D., et al. BMC Gastroenterol. 2017;14;17(1):53.
Other Resources:
https://www.naturalmedicinejournal.com/journal/2017-05/takeaways-2017-integrative-sibo-conferencePimentel, M. A New IBS Solution. Health Point Press, Sherman Oaks, CA. 2006.
