Small Intestine Bacterial Overgrowth: Often-Ignored Cause of Irritable Bowel Syndrome
by Allison Siebecker, ND, MSOM, LAc, and Steven Sandberg-Lewis, ND, DHANP
FIRST PLACE WINNER!Best of Naturopathic Medicine 2013
https://www.townsendletter.com/article/355-6-sibo-ibs-irritable-bowel-syndrome/
Our experience has been that naturopathic approaches to irritable bowel syndrome (IBS) tend to be highly successful. Often, uncovering and removing hidden food intolerances, adding mindfulness to a rushed approach to meals, or restoring production of digestive acid or enzymes is the key to resolving IBS. But what about those cases in which bloating, abdominal pain, constipation, or diarrhea remain unchanged? After more life-threatening diagnoses are ruled out, where do you turn?
Small intestine bacterial overgrowth (SIBO) is a condition in which abnormally large numbers of commensal bacteria are present in the small intestine. SIBO is a common cause of IBS – in fact it is involved in over half the cases of IBS and as high as 84% in one study using breath testing as the diagnostic marker.1,2 It accounts for 37% of cases wherein endoscopic cultures of aerobic bacteria are used for diagnosis.3 Eradication of this overgrowth leads to a 75% reduction in IBS symptoms.4 Bacterial overgrowth leads to impairment of digestion and absorption and produces excess quantities of hydrogen and/or methane gas. These gases are not produced by human cells but are the metabolic product of fermentation of carbohydrates by intestinal bacteria. When commensal bacteria (oral, small intestine or large intestine) multiply in the small intestine to the point of overgrowth, IBS is likely. Hydrogen/methane breath testing is the most widely used method of testing for this overgrowth. Stool testing has no value in diagnosing SIBO.
Symptoms of SIBO include:
• bloating/ abdominal gas
• flatulence, belching
• abdominal pain, discomfort, or cramps
• constipation, diarrhea or a mixture of the two
• heartburn
• nausea
• malabsorption: steatorrhea, anemia
• systemic symptoms: headache, joint/muscle pain, fatigue, rosacea
Other diseases associated with SIBO include hypothyroidism, lactose intolerance, Crohn’s disease, systemic sclerosis, celiac disease, chronic pancreatitis, diabetes with autonomic neuropathy, fibromyalgia and chronic regional pain syndrome, hepatic encephalopathy, nonalcoholic steatohepatitis, interstitial cystitis, restless leg syndrome, and acne rosacea.5–17
In our practices we have found that the following indicators increase the chances that a patient’s IBS is caused by SIBO:
- when a patient develops IBS following a bout of acute gastroenteritis.
• when a patient reports dramatic transient improvement in IBS symptoms after antibiotic treatment
• when a patient reports worsening of IBS symptoms from ingesting probiotic supplements which also contain prebiotics
• when a patient reports that eating more fiber increases constipation and other IBS symptoms
• when a celiac patient reports insufficient improvement in digestive symptoms even when following a gluten-free diet
• when a patient develops constipation type IBS (IBS-C) after taking opiates
• when a patient has chronic low ferritin levels with no other apparent cause
Mechanisms by which Overgrowth is Prevented
An important protective mechanism against SIBO is proper small intestine motility via the migrating motor complex because stasis promotes bacterial growth.18 Also key in prevention is gastric, pancreatic, and gall bladder secretion, since hydrochloric acid, enzymes, and bile are bactericidal/static.19 The use of proton pump inhibitors encourages overgrowth, especially of the hydrogen producing type.20,21 We also suspect an important role for proper ileocecal valve function in preventing reflux of colonic bacteria into the small intestine.22
Definition
Traditionally, ≥ 105 colony-forming units (CFU) per mL of proximal jejunal aspiration has been the definition of SIBO in culturing studies. ≥ 103 CFUs is now the suggested definition due to recent studies revealing ≤103 CFUs is the normal level in healthy controls.23,24 The bacteria most commonly overgrown are both:
Commensal anaerobes (do not require oxygen for growth)
- Bacteroides39%
- Lactobacillus25%
- Clostridium20%
Commensal aerobes (do require oxygen for growth)
- Streptococcus60%
- Escherichia coli36%
- Staphylococcus13%
- Klebsiella11%
- Escherichia coli37%
- Enterococcus species32%
- Klebsiella pneumonia24%
- Proteus mirabilis5%20,25
How SIBO Causes the Symptoms Of IBS
There are two main pathophysiological issues involved in SIBO. First, bacteria can ferment food meant for the host simply by their inappropriate location in the small intestine, which allows them premature exposure to host nutrition. Bacterial fermentation produces hydrogen and/or methane gas. Bacterial gas leads to the IBS symptoms of bloating, pain, altered bowel movements, eructation and flatulence (Figure 1). The quantity of gas may be extensive, causing bloating/distention.26 Excess gas can then exit the body as flatulence or eructation. The intestines are sensitive to pressure and therefore the pressure of distention can lead to abdominal pain. In addition, visceral hypersensitivity, a feature of IBS, may create a lower threshold for pain/discomfort and a hyperresponsiveness of muscular contraction in response to the gas, leading to cramps in some.27,28 The gases also affect bowel motility with hydrogen having a greater association with diarrhea and methane having an almost exclusive association with constipation.29,30
Figure 1
Methane has been shown to slow gastrointestinal motility by 59% in animal studies, and the volume of methane overproduction correlates with the severity of constipation.31,32 Therefore when both hydrogen and methane are present, diarrhea, constipation, or a mixture of both can be present based on the relative amounts of gases.29 The bacterial consumption and uptake of host nutrients, such as B12 and iron, can lead to macrocytic and/or microcytic anemia or chronic low ferritin, in addition to general malabsorption and malnutrition in more severe cases.8,33 The increased motility of diarrhea may also induce malabsorption. Finally, continuous fermentation of host nutrition by repeated exposure to daily meals, perpetuates bacterial overgrowth and its symptoms, creating a vicious cycle (Figure 1).
Second, bacteria damage the digestive and absorptive structure and function of the small intestine. This occurs because, unlike the large intestine, the small intestine is not designed for large colonization. The damage leads to both gastrointestinal and systemic symptoms (Figure 2). Key damaging factors are: bacterial deconjugation of bile, which creates fat malabsorption (steatorrhea, fat-soluble vitamin deficiency); bacterial digestion of disaccharide enzymes, which furthers carbohydrate malabsorption, fermentation, and gas; and increased intestinal permeability (leaky gut), which leads to systemic symptoms.34–38
Figure 2
Diagnosis of SIBO
As mentioned above, hydrogen/methane breath testing is the most common method of assessing SIBO. Instrumentation is available from Quintron Instrument Company in Milwaukee, Wisconsin. It provides a device called the Breathtracker, which is used to measure these gases following a 24-hour prep diet and an overnight fast. After collection of a fasting baseline specimen, a solution of lactulose – an unabsorbable synthetic sugar – is ingested as the substrate for bacterial fermentation. Lactulose is nonabsorbable because only bacteria, not humans, produce the enzymes to digest it. It takes the lactulose approximately 2 hours to traverse the small bowel. Glucose may also be used as a test substance, but because of its rapid absorption in the proximal small intestine, it may fail to identify more distal SIBO.24 Serial breath specimens are taken every 20 minutes during this time and for a third hour as well. Tests may be done at a facility with a Breathtracker or at home with a kit. Kit breath samples are exhaled into special vials similar to a vacutainer tube which stores the labeled sample until it can be delivered to the lab for analysis. In the Portland, Oregon, area, SIBO breath testing is available at our lab (NCNM Clinic Laboratory) as well as at the Oregon Health and Science University and Emanuel Hospital endoscopy centers. Out-of-town samples can be mailed, and other testing sites are available around the country. Not all labs have the equipment to test for methane. Methane testing is important because treatment is different for methane versus hydrogen.
Preparation for the test varies from lab to lab, but a typical prep diet is limited to white rice, fish/poultry/meat, eggs, clear beef or chicken broth (not bone broth or bouillon), oil, salt, and pepper. The purpose of the prep diet is to get a clear reaction to the test solution by reducing fermentable foods the day before. In some cases, two days of prep diet may be needed to reduce baseline gases to negative. Antibiotics should not be used for at least 2 weeks prior to an initial test; some sources recommend 4 weeks.39
Interpretation of the test varies among practitioners. The criteria provided by Quin Tron for a positive test are as follows:
- a rise over baseline in hydrogen production of 20 parts per million (ppm) or greater within 120 minutes after ingesting the test substrate
• a rise over baseline in methane production of 12 ppm or greater within 120 minutes after ingesting the test substrate
• a rise over baseline in the sum of hydrogen and methane production of 15 ppm or greater within 120 minutes after ingesting the test substrate
We have found that an absolute level of gases at or above the positive ppm levels provided by Quin Tron, without a rise over baseline, correlates well with clinical SIBO. This is especially true for methane gas, which can have a pattern of elevated baseline (over 12 ppm) which remains elevated for the duration of the test. In cases such as these, methane may only rise 5 ppm over baseline, but the ppm level is consistently above positive. Interpretation of elevated hydrogen or methane on the baseline specimen (pre-lactulose ingestion) is controversial, but we prefer to consider a high baseline to be a positive test.31,40
The classic positive for SIBO has been considered to be a double peak, with the first peak representing the SIBO and the second peak representing the normal large intestine bacteria. This is an infrequent presentation in our experience. More frequently we see one peak that rises highest in the third hour, representing distal SIBO and then the normal LI bacteria.
If the measured gases do not rise until after 120 minutes, it is possible that this is due to a prolonged transit time, which we have seen in patients with severe constipation. In such a patient with the expected symptom picture for constipation type SIBO, a significant rise at 140 minutes may be interpreted as a positive test.
Breath testing may be used in pediatric cases, so long as the child can follow instructions to blow. For those under 3 years old, testing is best done on site at a lab due to differences in collection methods versus at-home kits. Pediatric lactulose dosing is 1g/kg body weight with a maximum of 10 g (22 pounds and above receive the max/adult dose of 10 g).41 Lactulose requires a prescription.
Figure 3
Treatment of SIBO
In 2006, Pimentel shared his treatment algorithm for IBS with SIBO which included the use of either antibiotics, elemental diet or both.28 Our approach offers two additional options: diet and herbal antibiotics (Figure 3).
Diet
We advise diet (Specific Carbohydrate Diet or Gut and Psychology Syndrome Diet) for all SIBO patients.42,43 Since bacteria use carbohydrates as their energy source and ferment them to gas, a low-carbohydrate diet can directly reduce symptoms by decreasing the amount of gas produced.44 Reducing carbohydrates may also reduce the overall bacterial load as the food supply shrinks, though formal studies to validate this are lacking. These diets decrease polysaccharides, oligosaccharides, and disaccharides by eliminating all grains, starchy vegetables, lactose, sweeteners other than honey, and in the beginning, beans. Many patients experience a rapid and significant decrease in symptoms after starting a SIBO diet. The Specific Carbohydrate Diet (SCD) has been reported to have an 84% success rate for inflammatory bowel disease, a condition commonly associated with SIBO.45,46
Diet alone has proven successful for infants and children, but for adults one or more of the other three treatment options are often needed to reduce bacteria quickly, particularly in cases in which diet needs to be very restricted to obtain symptomatic relief. Additionally, any diet will always need to be customized to the individual by trial and error over time. That being said, following a diet prescription offers a place to start. We have found that using the SCD or Gut and Psychology Syndrome Diet (GAPS) as the core diet (Table 1), with the incorporation of the fruit and vegetable recommendations from the Low FODMAP Diet (Table 2), is an effective approach. The Low FODMAP Diet is an IBS treatment diet that has investigated the fermentable levels of carbohydrate foods (fruits, vegetables, and grains) and has a success rate of 76%.47 The FODMAP Diet is not specifically designed for SIBO and therefore does not eliminate polysaccharide and disaccharide sources such as grains, starch, starchy vegetables, and sucrose. Eliminating these poly- and disaccharides is essential in SIBO because SIBO creates a situation in which these normally well-absorbed carbohydrates, foods that usually go to feed the host, can now feed bacteria inappropriately located in the small intestine, creating symptoms and worsening the problem (Figure 1).
Low-carbohydrate diets are weight-loss diets. Particular attention must be paid to those who are low weight or underweight. If a low-carb SIBO diet is causing too much weight loss, this dietary strategy will need to be altered to allow for more carbohydrates. In these circumstances, one or more of the other three treatment options should be considered along with white rice, glucose, and other carbohydrate sources.
Diet is also essential for prevention, post SIBO treatment.
Elemental Diet
An elemental diet can be used in place of antibiotics or herbal antibiotics to rapidly decrease bacteria. Elemental diets are powdered predigested nutrients that are mixed with water and used in hospitals for various gastrointestinal disorders to give digestion a rest. The concept behind this treatment for SIBO is that the nutrients will be absorbed before having a chance to feed the bacteria, thus feeding the person but starving the bacteria. It is used in place of all meals, for 2 to 3 weeks, and has a success rate of 80% to 85%.48 Elemental diets are not protein powders or cleansing/detox formulas. They are available over the counter and are not covered by insurance, which can make this treatment course costly.
Antibiotics
The most studied and successful antibiotic for SIBO is rifaximin. It has a broad spectrum of activity and is nonabsorbable. Its nonabsorbability allows it to stay in the intestine, acting locally and it is therefore less likely to cause systemic side effects common to standard absorbable antibiotics.49
Rifaximin has up to a 91% success rate and is given at 550 mg t.i.d × 14 days.50,51
Additionally, rifaximin has several unique benefits: it does not cause yeast overgrowth, it decreases antibiotic resistance in bacteria by reducing plasmids, antibiotic resistance does not develop to it, making it effective for retreatments, and it is anti-inflammatory, decreasing intestinal inflammatory cytokines and inhibiting NF-kb via the PXR gene.52–54 Rifaximin is best used for SIBO when hydrogen is present, but when methane gas is present, double therapy of rifaximin plus neomycin (500 mg b.i.d. × 14 days) is more effective.55 Many gastroenterologists use metronidazole (250 mg t.i.d. × 14 days) as an alternative to neomycin (unpublished). Since different antibiotic regimens are recommended based on the gas type, breath testing is necessitated when considering this treatment.
Herbal Antibiotics
While there has only been one published report of herbal antibiotics in the treatment of SIBO, our experience is that they have similar effectiveness to antibiotics.56
We have used the following botanicals:
- Allium sativum,
- Hydrastis canadensis,
- and other berberine-containing herbs,
- Origanum vulgare,
- cinnamon, and
- Azadirachta indica.
We have used these as both single agents and in various combinations at dosages that are at the upper end of label suggestions × 30 days.
Specific single dosages we have used include
- allicin extract of garlic: 450 mg b.i.d.–t.i.d.,
- goldenseal/berberine: 5g q.d. in split dosage,
- emulsified oregano: 100 mg b.i.d., and
- neem: 300 mg t.i.d.
Our breath testing has validated the need for the longer treatment period of 30 days for herbal antibiotics compared with 14 days for antibiotics. We have also observed with this method prolonged die-off reactions, which can last for the duration of treatment course. Studies on herbal antibiotics for SIBO are needed, particularly to identify botanicals effective in reducing methane.
Prevention of SIBO
SIBO is a disease that relapses because eradication itself does not always correct the underlying cause.57,58 Pimentel’s 2006 treatment algorithm includes 2 essential preventions: diet and a prokinetic (motility agent). Our approach offers 3 optional additions: hydrochloric acid, probiotics, and brush border healing supplements (Figure 3).
Prokinetic
A key underlying cause of SIBO is thought to be deficiency of the migrating motor complex (MMC), which moves bacteria down into the large intestine during fasting at night and between meals.59 Prokinetics stimulate the MMC, symptomatically correcting this underlying cause.
Prokinetics studied for SIBO include
- low-dose naltrexone 2.5 mg q.d., h.s., or b.i.d.,
- low-dose erythromycin 50 mg h.s., and
- tegaserod 2–6 mg h.s.59,60
Tegaserod has a higher success rate for SIBO prevention versus erythromycin but has been withdrawn from the US for safety reasons.59 Prucalopride 1–4 mg h.s. is not yet available in the US but is a safer alternative to tegaserod.61 A trial removal of the prokinetic at ≥ 3 months is suggested but continued long-term use may be needed.28
Diet
A lower-carbohydrate diet is used in combination with a prokinetic to discourage a return of overgrowth of bacteria by limiting the food that they thrive on. Once the overgrowth is gone and small intestine damage has healed, the diet can be expanded beyond the strictness of the SCD and GAPS diets. The time frame for this is uncertain. To our knowledge, only one study has examined the rate of healing post SIBO, which found that intestinal permeability normalized four weeks after successful SIBO eradication in 75% of patients.37 While this report is very encouraging, it may or may not reflect the other repair needed post SIBO. Therefore we currently suggest continuing a SIBO diet for three months post successful eradication. At this point, the Cedars-Sinai Diet, FODMAP Diet, or a similar lower-carb diet may be adopted long term, as the patient tolerates.28,61 These diets allow more carbohydrates in the form of grains, gluten-free grains, sugar, and soy, though they still limit overall carbohydrate amounts.
Spacing meals 4 to 5 hours apart, with nothing ingested but water, allows migrating motor complex (MMC) to occur.28 We have found this to be very helpful clinically. If a low-carb SIBO diet does not correct hypoglycemia, this strategy will need to be altered to allow for more frequent meals.
Supplements
Hydrochloric acid or herbal bitter supplements, which encourage hydrochloric acid (HCl) secretion, may be used to decrease the load of incoming bacteria.62 When considering HCl supplementation, Heidelberg testing for HCl level and function is the gold standard and allows individualization of dosing.
Probiotics are a controversial intervention in SIBO because lactobacilli have been cultured in SIBO and there is concern about adding to the bacterial overload, particularly in this situation of dysfunctional MMC.25 Despite this, the few studies that have focused directly on SIBO have shown good results, with a SIBO eradication rate of 47% from Bacillus clausii as the only treatment, and a clinical improvement rate of 82% from Lactobacillus casei and plantarum, Streptococcus faecalis, and Bifidobacter brevis (Bioflora) as the only treatment.63,64 Probiotic yogurt containing Lactobacillus johnsonii normalized cytokine responses – reducing the low-grade chronic inflammation found in SIBO, after 4 weeks.65 We have used various multistrain and single probiotics as well as yogurt and cultured vegetables in our SIBO patients, with good results. A key point for the use of probiotic supplements in SIBO is to avoid prebiotics as main ingredients. Prebiotics are fermentable food for bacteria that can exacerbate symptoms during active SIBO and encourage bacterial growth post SIBO. Common prebiotics found in probiotic supplements include FOS (fructooligosaccharide), inulin, arabinogalactan, and GOS (galactoligosaccharide). Prebiotics may be tolerated in small amounts used as base ingredients, but this depends on the individual.
Brush border healing supplements may be given to assist the repair of small intestine tissue. While mucilaginous herbs are traditionally employed for this purpose (licorice, slippery elm, aloe vera, marshmallow), their use is controversial post SIBO, due to their high level of mucopolysaccharides, which could encourage bacterial regrowth.
Specific nutrients that we have used include
- colostrum: 2–6 g q.d.,
- L-glutamine: 375 mg–1500 mg q.d.,
- zinc carnosine: 75–150 mg q.d.,
- vitamins A and D, often given as cod liver oil: 1 Tbs q.d.,
- curcumin: 400 mg–3 g q.d.,
- resveratrol: 250 mg–2 g q.d.,
- glutathione (oral liposomal): 50–425 mg q.d. or glutathione precursor N-acetylcysteine 200–600 mg q.d.
Supplements are given for one to three months, though may be continued long term for general benefit. Higher dosages of curcumin and resveratrol are given for two weeks for the purpose of downregulating NF-kb, a mediator of increased intestinal permeability, and then reduced to maintenance levels. 66–68
In our practices we have found that the following circumstances increase the chances for an unsatisfactory patient outcome:
- Failure to continue treatment courses until SIBO is eradicated (negative breath test or patient ≥90% better).This crucial process of successive treatment is indicated by the long go-back arrow on the right side of our algorithm (Figure 3).
• Failure to use double antibiotic therapy for methane producers. Methanogenic bacteria need different antibiotic treatment than hydrogen-producing bacteria.
• Failure to utilize breath testing to identify if the patient has SIBO, the type of gas he/she produces, and the overall level of gas. This information is necessary for diagnosis, treatment choice, duration, and prognosis.
• Failure to use a prokinetic immediately following treatment. Prokinetics along with diet are needed to prevent relapse of this commonly recurring condition.
• Failure to use a low-carb preventative diet following treatment. Diet along with prokinetics are needed to prevent relapse of this commonly recurring condition.
• Failure to tailor diet to individual tolerances with personal experimentation. No fixed diet can predict an individual’s complex bacterial, digestive, absorptive, immunological, and genetic circumstances; therefore customizing is necessary.
• Failure to identify underlying causative conditions. A recent report found the following conditions led to a poor response to antibiotics: anatomical abnormalities, chronic narcotic use, Addison’s disease, scleroderma, colonic inertia, inflammatory bowel disease, and NSAID-induced intestinal ulceration.69
Notes
1. Peralta S et al. Small intestine bacterial overgrowth and irritable bowel syndrome-related symptoms: experience with Rifaximin. World J Gastroenterol. 2009 Jun 7;15(21):2628–2631.
2. Lin HC et al. Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome. JAMA. 2004 Aug 18;292(7):852–858.
3. Pyleris E et al. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci. 2012 May;57(5):1321–1329.
4. Pimentel M et al. The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial. Ann Intern Med. 2006 Oct 17;145(8):557–563.
5. Lauritano EC et al. Association between hypothyroidism and small intestinal bacterial overgrowth. J Clin Endocrinol Metab. 2007 Nov;92(11):4180–4184.
6. Almeida JA et al. Lactose malabsorption in the elderly: role of small intestinal bacterial overgrowth. Scand J Gastroenterol. 2008;43(2):146–154.
7. Klaus J et al. Small intestinal bacterial overgrowth mimicking acute flare as a pitfall in patients with Crohn’s Disease. BMC Gastroenterol. 2009 Jul 30;9:61.
8. Marie I, Ducrotté P, Denis P, Menard JF, Levesque H. Small intestinal bacterial overgrowth in systemic sclerosis. Rheumatology (Oxford). 2009 Oct;48(10):1314–1319. Epub 2009 Aug 20.
9. Rubio-Tapia A et al. Prevalence of small intestine bacterial overgrowth diagnosed by quantitative culture of intestinal aspirate in celiac disease. J Clin Gastroenterol. 2009 Feb;43(2):157–161.
10. Mancilla AC et al. [Small intestine bacterial overgrowth in patients with chronic pancreatitis]. Rev Med Chil. 2008 Aug;136(8):976–980.
11. Ojetti V et al. Small bowel bacterial overgrowth and type 1 diabetes. Eur Rev Med Pharmacol Sci. 2009 Nov–Dec;13(6):419–423.
12. Goebel A et al. Altered intestinal permeability in patients with primary fibromyalgia and in patients with complex regional pain syndrome. Rheumatology (Oxford). 2008 Aug;47(8):1223–1227.
13. Gupta A et al. Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy. J Hepatol. 2010 Nov;53(5):849–855.
14. Shanab AA et al. Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8. Dig Dis Sci. 2011 May;56(5):1524–1534.
15. Weinstock LB, Klutke CG, Lin HC. Small intestinal bacterial overgrowth in patients with interstitial cystitis and gastrointestinal symptoms. Dig Dis Sci. 2008 May;53(5):1246–1251.
16. Weinstock LB, Walters AS, Restless legs syndrome is associated with irritable bowel syndrome and small intestinal bacterial overgrowth. Sleep Med. 2011 Jun;12(6):610–613.
17. Parodi A et al. Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Clin Gastroenterol Hepatol. 2008 Jul;6(7):759–764.
18. Husebye E. The patterns of small bowel motility: physiology and implications in organic disease and functional disorders. Neurogastroenterol Motil. 1999 Jun;11(3):141–161.
19. Bures J. 2010 Small intestinal bacterial overgrowth syndrome. World J Gastroenterol. 2010 Jun 28;16(24):2978–2990.
20. Pyleris E et al. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci. 2012 May;57(5):1321–1329.
21. Williams C et al. Occurrence and significance of gastric colonization during acid-inhibitory therapy. Best Pract Res Clin Gastroenterol. 2001 Jun;15(3):511–521.
22. Machado WM et al. The small bowel flora in individuals with cecoileal reflux. Arq Gastroenterol. 2008 Jul–Sep;45(3):212–218.
23. Khoshini R, Dai SC, Lezcano S, Pimentel M. A systematic review of diagnostic tests for small intestinal bacterial overgrowth. Dig Dis Sci. 2008 Jun;53(6):1443–1454.
24. Pimentel M. Gut microbes and irritable bowel syndrome [webcast]. July 20, 2012. GI Health Foundation. http://www.gihealthfoundation.org/coe/ibs/webcast/2012/july/MPimentel/?link=2012/
july/MPimentel&cme_proj_id=12&actionPage=topics/Gut_Microbes_and_
IBS/request-for-credit.cfm?cme_proj_id=12. (One link: Three lines) Accessed October 27, 2012.
25. Bouhnik Y et al. Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome. Am J Gastroenterol. 1999 May;94(5):1327–1331.
26. Youn YH, Park JS, Jahng JH, et al. Relationships among the lactulose breath test, intestinal gas volume, and gastrointestinal symptoms in patients with irritable bowel syndrome. Dig Dis Sci. 2011 Jul;56(7):2059–2066. Epub 2011 Jan 15.
27. Elsenbruch S. Abdominal pain in irritable bowel syndrome: a review of putative psychological, neural and neuro-immune mechanisms. Brain Behav Immun. 2011 Mar;25(3):386–394. Epub 2010 Nov 20.
28. Pimentel M. A New IBS Solution. Sherman Oaks, CA: Health Point Press; 2006.
29. Pimentel M, Mayer AG, Park S, Chow EJ, Hasan A, Kong Y. Methane production during lactulose breath test is associated with gastrointestinal disease presentation. Dig Dis Sci. 2003 Jan;48(1):86–92.
30. Kunkel D et al. Methane on breath testing is associated with constipation: a systematic review and meta-analysis. Dig Dis Sci. 2011 Jun;56(6):1612–1618.
31. Pimentel M, Lin HC, Enayati P, et al. Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity. Am J Physiol Gastrointest Liver Physiol. 2006 Jun;290(6):G1089–G1095. Epub 2005 Nov 17.
32. Chatterjee S et al. The degree of breath methane production in IBS correlates with the severity of constipation. Am J Gastroenterol. 2007 Apr;102(4):837–841.
33. Singh VV, Toskes PP. Small bowel bacterial overgrowth: presentation, diagnosis, and treatment. Curr Treat Options Gastroenterol. 2004 Feb;7(1):19–28.
34. DiBaise JK. Nutritional consequences of small intestinal bacterial overgrowth. Prac Gastroenterol. 2008;69:15–28.
36. Prizont R. Glycoprotein degradation in the blind loop syndrome: identification of glycosidases in jejunal contents. J Clin Invest. 1981 Feb;67(2):336–344.
37. Lauritano EC, Valenza V, Sparano L, et al. Small intestinal bacterial overgrowth and intestinal permeability. Scand J Gastroenterol. 2010 Sep;45(9):1131–1132.
38. Resnick C. Nutritional protocol for the treatment of intestinal permeability defects and related conditions. Nat Med J. March 2010.
39. Eisenmann A et al. Implementation and interpretation of hydrogen breath tests. J Breath Res. 2008 Dec;2(4):046002.
40. Quigley EM, Quera R. Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics. Gastroenterology. 2006 Feb;130(2 Suppl 1):S78–S90.
41. Quin Tron Instrument Company Inc. Quin Tron Catalog and Information. 2012:22.
42. Gottschall E. Breaking the Vicious Cycle. Baltimore, ON: Kirkton Press Ltd.; 1994.
43. Campbell-McBride N. Gut and Psychology Syndrome. Cambridge: Medinform Publishing; 2004.
44. Ong DK, Mitchell SB, Barrett JS, et al. Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome. J Gastroenterol Hepatol. 2010 Aug;25(8):1366–1373.
45. Nieves R, Jackson RT. Specific carbohydrate diet in treatment of inflammatory bowel disease. Tenn Med. 2004 Sep;97(9):407.
46. Choung RS, Ruff KC, Malhotra A, et al. Clinical predictors of small intestinal bacterial overgrowth by duodenal aspirate culture. Aliment Pharmacol Ther. 2011 May;33(9):1059–1067. doi: 10.1111/j.1365-2036.2011.04625.x. Epub 2011 Mar 13.
47. Staudacher HM, Whelan K, Irving PM, Lomer MC. Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome. J Hum Nutr Diet. 2011 Oct;24(5):487–495. doi:10.1111/j.1365-277X.2011.01162.x. Epub 2011 May 25.
48. Pimentel M, Constantino T, Kong Y, Bajwa M, Rezaei A, Park S. A 14-day elemental diet is highly effective in normalizing the lactulose breath test. Dig Dis Sci. 2004 Jan;49(1):73–77.
49. Scarpignato C, Pelosini I. Experimental and clinical pharmacology of rifaximin, a gastrointestinal selective antibiotic. Digestion. 2006;73 Suppl 1:13–27. Epub 2006 Feb 8.
50. Lombardo L, Foti M, Ruggia O, Chiecchio A. Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy. Clin Gastroenterol Hepatol. June 2010;8(6):504–508.
51. Pimentel M, Lembo A, Chey WD, et al.; TARGET Study Group. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011 Jan 6;364(1):22–32.
52. Yang J, Lee HR, Low K, Chatterjee S, Pimentel M. Rifaximin versus other antibiotics in the primary treatment and retreatment of bacterial overgrowth in IBS. Dig Dis Sci. 2008 Jan;53(1):169–74. Epub 2007 May 23.
53. Debbia EA, Maioli E, Roveta S, Marchese A. Effects of rifaximin on bacterial virulence mechanisms at supra- and sub-inhibitory concentrations. J Chemother. 2008 Apr;20(2):186–194.
54. Mencarelli A, Renga B, Palladino G, et al. Inhibition of NF-kb by a PXR-dependent pathway mediates counter-regulatory activities of rifaximin on innate immunity in intestinal epithelial cells. Eur J Pharmacol. 2011 Oct 1;668(1–2):317–324. Epub 2011 Jul 26.
55. Low K, Hwang L, Hua J, Zhu A, Morales W, Pimentel M. A combination of rifaximin and neomycin is most effective in treating irritable bowel syndrome patients with methane on lactulose breath test. J Clin Gastroenterol. 2010 Sep;44(8):547–550.
56. Logan AC, Beaulne TM. The treatment of small intestinal bacterial overgrowth with enteric-coated peppermint oil: a case report. Altern Med Rev. 2002 Oct;7(5):410–417.
57. Pimentel M, Morales W, Lezcano S, Sun-Chuan D, Low K, Yang J. Low-dose nocturnal tegaserod or erythromycin delays symptom recurrence after treatment of irritable bowel syndrome based on presumed bacterial overgrowth. Gastroenterol Hepatol (N Y). 2009 Jun;5(6):435–442.
58. Pimentel M. An evidence-based treatment algorithm for IBS based on a bacterial/SIBO hypothesis: Part 2. Am J Gastroenterol. 2010 Jun;105(6):1227–30.
59. Ploesser J, Weinstock LB, Thomas E. Low Dose Naltrexone: Side Effects and Efficacy in Gastrointestinal Disorders. International Journal of Pharmaceutical Compounding; March 2010.
60. Manabe N, Rao AS, Wong BS, Camilleri M. Emerging pharmacologic therapies for irritable bowel syndrome. Curr Gastroenterol Rep. 2010 Oct;12(5):408–16.
61. Gibson PR, Shepherd SJ. Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach. J Gastroenterol Hepatol. 2010 Feb;25(2):252–8. Review.
62. Bowman, G. The Gut, the Brain and the Functional GI Disorders. Functional Gastroenterology Seminar: Level 1. Winter 2010, p. 19.
63. Gabrielli M, Lauritano EC, Scarpellini E, Lupascu A, Ojetti V, Gasbarrini G, Silveri NG, Gasbarrini A. Bacillus clausii as a treatment of small intestinal bacterial overgrowth. Am J Gastroenterol. 2009 May;104(5):1327–8. Epub 2009 Apr 7.
64. Soifer LO, Peralta D, Dima G, Besasso H. Comparative clinical efficacy of a probiotic vs. an antibiotic in the treatment of patients with intestinal bacterial overgrowth and chronic abdominal functional distension: a pilot study. Acta Gastroenterol Latinoam. 2010 Dec;40(4):323–7.
65. Schiffrin EJ, Parlesak A, Bode C, Bode JC, van’t Hof MA, Grathwohl D, Guigoz Y. Probiotic yogurt in the elderly with intestinal bacterial overgrowth: endotoxaemia and innate immune functions. Br J Nutr. 2009 Apr;101(7):961–6.
66. Ruland J. Return to homeostasis: downregulation of NF-κB responses. Nat Immunol. 2011 Jun 19;12(8):709–14. doi: 10.1038/ni.2055.
67. Al-Sadi RM, Ma TY. IL-1beta causes an increase in intestinal epithelial tight junction permeability. J Immunol. 2007 Apr 1;178(7):4641–9.
68. Csaki C, Mobasheri A, Shakibaei M. Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1beta-induced NF-kappaB-mediated inflammation and apoptosis. Arthritis Res Ther. 2009;11(6):R165. Epub 2009 Nov 4.
69. Chou J, Tabrizi R, Pimentel M, Sokol T. S1326 Presumed IBS Subjects With Short Remission After Antibiotic Therapy Often Have Secondary Causes for Their Symptoms. Gastroenterology, Volume 138, Issue 5, Supplement 1 , Pages S–229, May 2010.
Allison Siebecker, ND, MSOM, LAc
Steven Sandberg-Lewis, ND, DHANP
NCNM Clinic
3025 SW Corbett Ave.
Portland, Oregon 97211
Small Intestine Bacterial Overgrowth: Often-Ignored Cause of Irritable Bowel Syndrome
by Allison Siebecker, ND, MSOM, LAc, and Steven Sandberg-Lewis, ND, DHANP
FIRST PLACE WINNER!
Best of Naturopathic Medicine 2013
Our experience has been that naturopathic approaches to irritable bowel syndrome (IBS) tend to be highly successful. Often, uncovering and removing hidden food intolerances, adding mindfulness to a rushed approach to meals, or restoring production of digestive acid or enzymes is the key to resolving IBS. But what about those cases in which bloating, abdominal pain, constipation, or diarrhea remain unchanged? After more life-threatening diagnoses are ruled out, where do you turn?
Small intestine bacterial overgrowth (SIBO) is a condition in which abnormally large numbers of commensal bacteria are present in the small intestine. SIBO is a common cause of IBS – in fact it is involved in over half the cases of IBS and as high as 84% in one study using breath testing as the diagnostic marker.1,2 It accounts for 37% of cases wherein endoscopic cultures of aerobic bacteria are used for diagnosis.3 Eradication of this overgrowth leads to a 75% reduction in IBS symptoms.4 Bacterial overgrowth leads to impairment of digestion and absorption and produces excess quantities of hydrogen and/or methane gas. These gases are not produced by human cells but are the metabolic product of fermentation of carbohydrates by intestinal bacteria. When commensal bacteria (oral, small intestine or large intestine) multiply in the small intestine to the point of overgrowth, IBS is likely. Hydrogen/methane breath testing is the most widely used method of testing for this overgrowth. Stool testing has no value in diagnosing SIBO.
Symptoms of SIBO include:
• bloating/ abdominal gas
• flatulence, belching
• abdominal pain, discomfort, or cramps
• constipation, diarrhea or a mixture of the two
• heartburn
• nausea
• malabsorption: steatorrhea, anemia
• systemic symptoms: headache, joint/muscle pain, fatigue, rosacea
Other diseases associated with SIBO include hypothyroidism, lactose intolerance, Crohn’s disease, systemic sclerosis, celiac disease, chronic pancreatitis, diabetes with autonomic neuropathy, fibromyalgia and chronic regional pain syndrome, hepatic encephalopathy, nonalcoholic steatohepatitis, interstitial cystitis, restless leg syndrome, and acne rosacea.5–17
In our practices we have found that the following indicators increase the chances that a patient’s IBS is caused by SIBO:
• when a patient develops IBS following a bout of acute gastroenteritis.
• when a patient reports dramatic transient improvement in IBS symptoms after antibiotic treatment
• when a patient reports worsening of IBS symptoms from ingesting probiotic supplements which also contain prebiotics
• when a patient reports that eating more fiber increases constipation and other IBS symptoms
• when a celiac patient reports insufficient improvement in digestive symptoms even when following a gluten-free diet
• when a patient develops constipation type IBS (IBS-C) after taking opiates
• when a patient has chronic low ferritin levels with no other apparent cause
Mechanisms by which Overgrowth is Prevented
An important protective mechanism against SIBO is proper small intestine motility via the migrating motor complex because stasis promotes bacterial growth.18 Also key in prevention is gastric, pancreatic, and gall bladder secretion, since hydrochloric acid, enzymes, and bile are bactericidal/static.19 The use of proton pump inhibitors encourages overgrowth, especially of the hydrogen producing type.20,21 We also suspect an important role for proper ileocecal valve function in preventing reflux of colonic bacteria into the small intestine.22
Definition
Traditionally, ≥ 105 colony-forming units (CFU) per mL of proximal jejunal aspiration has been the definition of SIBO in culturing studies. ≥ 103 CFUs is now the suggested definition due to recent studies revealing ≤103 CFUs is the normal level in healthy controls.23,24 The bacteria most commonly overgrown are both commensal anaerobes (Bacteroides 39%, Lactobacillus 25%, Clostridium 20%) and commensal aerobes (Streptococcus 60%, Escherichia coli 36%, Staphylococcus 13%, Klebsiella 11%, Escherichia coli 37%, Enterococcus spp 32%, Klebsiella pneumonia 24%, Proteus mirabilis 6.5%).20,25
How SIBO Causes the Symptoms Of IBS
There are two main pathophysiological issues involved in SIBO. First, bacteria can ferment food meant for the host simply by their inappropriate location in the small intestine, which allows them premature exposure to host nutrition. Bacterial fermentation produces hydrogen and/or methane gas. Bacterial gas leads to the IBS symptoms of bloating, pain, altered bowel movements, eructation and flatulence (Figure 1). The quantity of gas may be extensive, causing bloating/distention.26 Excess gas can then exit the body as flatulence or eructation. The intestines are sensitive to pressure and therefore the pressure of distention can lead to abdominal pain. In addition, visceral hypersensitivity, a feature of IBS, may create a lower threshold for pain/discomfort and a hyperresponsiveness of muscular contraction in response to the gas, leading to cramps in some.27,28 The gases also affect bowel motility with hydrogen having a greater association with diarrhea and methane having an almost exclusive association with constipation.29,30
Figure 1
Methane has been shown to slow gastrointestinal motility by 59% in animal studies, and the volume of methane overproduction correlates with the severity of constipation.31,32 Therefore when both hydrogen and methane are present, diarrhea, constipation, or a mixture of both can be present based on the relative amounts of gases.29 The bacterial consumption and uptake of host nutrients, such as B12 and iron, can lead to macrocytic and/or microcytic anemia or chronic low ferritin, in addition to general malabsorption and malnutrition in more severe cases.8,33 The increased motility of diarrhea may also induce malabsorption. Finally, continuous fermentation of host nutrition by repeated exposure to daily meals, perpetuates bacterial overgrowth and its symptoms, creating a vicious cycle (Figure 1).
Second, bacteria damage the digestive and absorptive structure and function of the small intestine. This occurs because, unlike the large intestine, the small intestine is not designed for large colonization. The damage leads to both gastrointestinal and systemic symptoms (Figure 2). Key damaging factors are: bacterial deconjugation of bile, which creates fat malabsorption (steatorrhea, fat-soluble vitamin deficiency); bacterial digestion of disaccharide enzymes, which furthers carbohydrate malabsorption, fermentation, and gas; and increased intestinal permeability (leaky gut), which leads to systemic symptoms.34–38
Figure 2
Diagnosis of SIBO
As mentioned above, hydrogen/methane breath testing is the most common method of assessing SIBO. Instrumentation is available from Quintron Instrument Company in Milwaukee, Wisconsin. It provides a device called the Breathtracker, which is used to measure these gases following a 24-hour prep diet and an overnight fast. After collection of a fasting baseline specimen, a solution of lactulose – an unabsorbable synthetic sugar – is ingested as the substrate for bacterial fermentation. Lactulose is nonabsorbable because only bacteria, not humans, produce the enzymes to digest it. It takes the lactulose approximately 2 hours to traverse the small bowel. Glucose may also be used as a test substance, but because of its rapid absorption in the proximal small intestine, it may fail to identify more distal SIBO.24 Serial breath specimens are taken every 20 minutes during this time and for a third hour as well. Tests may be done at a facility with a Breathtracker or at home with a kit. Kit breath samples are exhaled into special vials similar to a vacutainer tube which stores the labeled sample until it can be delivered to the lab for analysis. In the Portland, Oregon, area, SIBO breath testing is available at our lab (NCNM Clinic Laboratory) as well as at the Oregon Health and Science University and Emanuel Hospital endoscopy centers. Out-of-town samples can be mailed, and other testing sites are available around the country. Not all labs have the equipment to test for methane. Methane testing is important because treatment is different for methane versus hydrogen.
Preparation for the test varies from lab to lab, but a typical prep diet is limited to white rice, fish/poultry/meat, eggs, clear beef or chicken broth (not bone broth or bouillon), oil, salt, and pepper. The purpose of the prep diet is to get a clear reaction to the test solution by reducing fermentable foods the day before. In some cases, two days of prep diet may be needed to reduce baseline gases to negative. Antibiotics should not be used for at least 2 weeks prior to an initial test; some sources recommend 4 weeks.39
Interpretation of the test varies among practitioners. The criteria provided by Quin Tron for a positive test are as follows:
- a rise over baseline in hydrogen production of 20 parts per million (ppm) or greater within 120 minutes after ingesting the test substrate
• a rise over baseline in methane production of 12 ppm or greater within 120 minutes after ingesting the test substrate
• a rise over baseline in the sum of hydrogen and methane production of 15 ppm or greater within 120 minutes after ingesting the test substrate
We have found that an absolute level of gases at or above the positive ppm levels provided by Quin Tron, without a rise over baseline, correlates well with clinical SIBO. This is especially true for methane gas, which can have a pattern of elevated baseline (over 12 ppm) which remains elevated for the duration of the test. In cases such as these, methane may only rise 5 ppm over baseline, but the ppm level is consistently above positive. Interpretation of elevated hydrogen or methane on the baseline specimen (pre-lactulose ingestion) is controversial, but we prefer to consider a high baseline to be a positive test.31,40
The classic positive for SIBO has been considered to be a double peak, with the first peak representing the SIBO and the second peak representing the normal large intestine bacteria. This is an infrequent presentation in our experience. More frequently we see one peak that rises highest in the third hour, representing distal SIBO and then the normal LI bacteria.
If the measured gases do not rise until after 120 minutes, it is possible that this is due to a prolonged transit time, which we have seen in patients with severe constipation. In such a patient with the expected symptom picture for constipation type SIBO, a significant rise at 140 minutes may be interpreted as a positive test.
Breath testing may be used in pediatric cases, so long as the child can follow instructions to blow. For those under 3 years old, testing is best done on site at a lab due to differences in collection methods versus at-home kits. Pediatric lactulose dosing is 1g/kg body weight with a maximum of 10 g (22 pounds and above receive the max/adult dose of 10 g).41 Lactulose requires a prescription.
Figure 3
Treatment of SIBO
In 2006, Pimentel shared his treatment algorithm for IBS with SIBO which included the use of either antibiotics, elemental diet or both.28 Our approach offers two additional options: diet and herbal antibiotics (Figure 3).
Diet
We advise diet (Specific Carbohydrate Diet or Gut and Psychology Syndrome Diet) for all SIBO patients.42,43 Since bacteria use carbohydrates as their energy source and ferment them to gas, a low-carbohydrate diet can directly reduce symptoms by decreasing the amount of gas produced.44 Reducing carbohydrates may also reduce the overall bacterial load as the food supply shrinks, though formal studies to validate this are lacking. These diets decrease polysaccharides, oligosaccharides, and disaccharides by eliminating all grains, starchy vegetables, lactose, sweeteners other than honey, and in the beginning, beans. Many patients experience a rapid and significant decrease in symptoms after starting a SIBO diet. The Specific Carbohydrate Diet (SCD) has been reported to have an 84% success rate for inflammatory bowel disease, a condition commonly associated with SIBO.45,46
Diet alone has proven successful for infants and children, but for adults one or more of the other three treatment options are often needed to reduce bacteria quickly, particularly in cases in which diet needs to be very restricted to obtain symptomatic relief. Additionally, any diet will always need to be customized to the individual by trial and error over time. That being said, following a diet prescription offers a place to start. We have found that using the SCD or Gut and Psychology Syndrome Diet (GAPS) as the core diet (Table 1), with the incorporation of the fruit and vegetable recommendations from the Low FODMAP Diet (Table 2), is an effective approach. The Low FODMAP Diet is an IBS treatment diet that has investigated the fermentable levels of carbohydrate foods (fruits, vegetables, and grains) and has a success rate of 76%.47 The FODMAP Diet is not specifically designed for SIBO and therefore does not eliminate polysaccharide and disaccharide sources such as grains, starch, starchy vegetables, and sucrose. Eliminating these poly- and disaccharides is essential in SIBO because SIBO creates a situation in which these normally well-absorbed carbohydrates, foods that usually go to feed the host, can now feed bacteria inappropriately located in the small intestine, creating symptoms and worsening the problem (Figure 1).
Low-carbohydrate diets are weight-loss diets. Particular attention must be paid to those who are low weight or underweight. If a low-carb SIBO diet is causing too much weight loss, this dietary strategy will need to be altered to allow for more carbohydrates. In these circumstances, one or more of the other three treatment options should be considered along with white rice, glucose, and other carbohydrate sources.
Diet is also essential for prevention, post SIBO treatment.
Elemental Diet
An elemental diet can be used in place of antibiotics or herbal antibiotics to rapidly decrease bacteria. Elemental diets are powdered predigested nutrients that are mixed with water and used in hospitals for various gastrointestinal disorders to give digestion a rest. The concept behind this treatment for SIBO is that the nutrients will be absorbed before having a chance to feed the bacteria, thus feeding the person but starving the bacteria. It is used in place of all meals, for 2 to 3 weeks, and has a success rate of 80% to 85%.48 Elemental diets are not protein powders or cleansing/detox formulas. They are available over the counter and are not covered by insurance, which can make this treatment course costly.
Antibiotics
The most studied and successful antibiotic for SIBO is rifaximin. It has a broad spectrum of activity and is nonabsorbable. Its nonabsorbability allows it to stay in the intestine, acting locally and it is therefore less likely to cause systemic side effects common to standard absorbable antibiotics.49 Rifaximin has up to a 91% success rate and is given at 550 mg t.i.d × 14 days.50,51 Additionally, rifaximin has several unique benefits: it does not cause yeast overgrowth, it decreases antibiotic resistance in bacteria by reducing plasmids, antibiotic resistance does not develop to it, making it effective for retreatments, and it is anti-inflammatory, decreasing intestinal inflammatory cytokines and inhibiting NF-kb via the PXR gene.52–54 Rifaximin is best used for SIBO when hydrogen is present, but when methane gas is present, double therapy of rifaximin plus neomycin (500 mg b.i.d. × 14 days) is more effective.55 Many gastroenterologists use metronidazole (250 mg t.i.d. × 14 days) as an alternative to neomycin (unpublished). Since different antibiotic regimens are recommended based on the gas type, breath testing is necessitated when considering this treatment.
Herbal Antibiotics
While there has only been one published report of herbal antibiotics in the treatment of SIBO, our experience is that they have similar effectiveness to antibiotics.56 We have used the following botanicals: Allium sativum, Hydrastis canadensis, and other berberine-containing herbs, Origanum vulgare, cinnamon, and Azadirachta indica. We have used these as both single agents and in various combinations at dosages that are at the upper end of label suggestions × 30 days. Specific single dosages we have used include allicin extract of garlic: 450 mg b.i.d.–t.i.d., goldenseal/berberine: 5g q.d. in split dosage, emulsified oregano: 100 mg b.i.d., and neem: 300 mg t.i.d. Our breath testing has validated the need for the longer treatment period of 30 days for herbal antibiotics compared with 14 days for antibiotics. We have also observed with this method prolonged die-off reactions, which can last for the duration of treatment course. Studies on herbal antibiotics for SIBO are needed, particularly to identify botanicals effective in reducing methane.
Prevention of SIBO
SIBO is a disease that relapses because eradication itself does not always correct the underlying cause.57,58 Pimentel’s 2006 treatment algorithm includes 2 essential preventions: diet and a prokinetic (motility agent). Our approach offers 3 optional additions: hydrochloric acid, probiotics, and brush border healing supplements (Figure 3).
Prokinetic
A key underlying cause of SIBO is thought to be deficiency of the migrating motor complex (MMC), which moves bacteria down into the large intestine during fasting at night and between meals.59 Prokinetics stimulate the MMC, symptomatically correcting this underlying cause. Prokinetics studied for SIBO include low-dose naltrexone 2.5 mg q.d., h.s., or b.i.d., low-dose erythromycin 50 mg h.s., and tegaserod 2–6 mg h.s.59,60 Tegaserod has a higher success rate for SIBO prevention versus erythromycin, but has been withdrawn from the US for safety reasons.59 Prucalopride 1–4 mg h.s. is not yet available in the US but is a safer alternative to tegaserod.61 A trial removal of the prokinetic at ≥ 3 months is suggested but continued long-term use may be needed.28
Diet
A lower-carbohydrate diet is used in combination with a prokinetic to discourage a return of overgrowth of bacteria by limiting the food that they thrive on. Once the overgrowth is gone and small intestine damage has healed, the diet can be expanded beyond the strictness of the SCD and GAPS diets. The time frame for this is uncertain. To our knowledge, only one study has examined the rate of healing post SIBO, which found that intestinal permeability normalized four weeks after successful SIBO eradication in 75% of patients.37 While this report is very encouraging, it may or may not reflect the other repair needed post SIBO. Therefore we currently suggest continuing a SIBO diet for three months post successful eradication. At this point, the Cedars-Sinai Diet, FODMAP Diet, or a similar lower-carb diet may be adopted long term, as the patient tolerates.28,61 These diets allow more carbohydrates in the form of grains, gluten-free grains, sugar, and soy, though they still limit overall carbohydrate amounts.
Spacing meals 4 to 5 hours apart, with nothing ingested but water, allows migrating motor complex (MMC) to occur.28 We have found this to be very helpful clinically. If a low-carb SIBO diet does not correct hypoglycemia, this strategy will need to be altered to allow for more frequent meals.
Supplements
Hydrochloric acid or herbal bitter supplements, which encourage hydrochloric acid (HCl) secretion, may be used to decrease the load of incoming bacteria.62 When considering HCl supplementation, Heidelberg testing for HCl level and function is the gold standard and allows individualization of dosing.
Probiotics are a controversial intervention in SIBO because lactobacilli have been cultured in SIBO and there is concern about adding to the bacterial overload, particularly in this situation of dysfunctional MMC.25 Despite this, the few studies that have focused directly on SIBO have shown good results, with a SIBO eradication rate of 47% from Bacillus clausii as the only treatment, and a clinical improvement rate of 82% from Lactobacillus casei and plantarum, Streptococcus faecalis, and Bifidobacter brevis (Bioflora) as the only treatment.63,64 Probiotic yogurt containing Lactobacillus johnsonii normalized cytokine responses – reducing the low-grade chronic inflammation found in SIBO, after 4 weeks.65 We have used various multistrain and single probiotics as well as yogurt and cultured vegetables in our SIBO patients, with good results. A key point for the use of probiotic supplements in SIBO is to avoid prebiotics as main ingredients. Prebiotics are fermentable food for bacteria that can exacerbate symptoms during active SIBO and encourage bacterial growth post SIBO. Common prebiotics found in probiotic supplements include FOS (fructooligosaccharide), inulin, arabinogalactan, and GOS (galactoligosaccharide). Prebiotics may be tolerated in small amounts used as base ingredients, but this depends on the individual.
Brush border healing supplements may be given to assist the repair of small intestine tissue. While mucilaginous herbs are traditionally employed for this purpose (licorice, slippery elm, aloe vera, marshmallow), their use is controversial post SIBO, due to their high level of mucopolysaccharides, which could encourage bacterial regrowth. Specific nutrients that we have used include colostrum: 2–6 g q.d., L-glutamine: 375 mg–1500 mg q.d., zinc carnosine: 75–150 mg q.d., vitamins A and D, often given as cod liver oil: 1 Tbs q.d., curcumin: 400 mg–3 g q.d., resveratrol: 250 mg–2 g q.d., glutathione (oral liposomal): 50–425 mg q.d. or glutathione precursor N-acetylcysteine 200–600 mg q.d. Supplements are given for one to three months, though may be continued long term for general benefit. Higher dosages of curcumin and resveratrol are given for two weeks for the purpose of downregulating NF-kb, a mediator of increased intestinal permeability, and then reduced to maintenance levels. 66–68
In our practices we have found that the following circumstances increase the chances for an unsatisfactory patient outcome:
- Failure to continue treatment courses until SIBO is eradicated (negative breath test or patient ≥90% better).This crucial process of successive treatment is indicated by the long go-back arrow on the right side of our algorithm (Figure 3).
• Failure to use double antibiotic therapy for methane producers. Methanogenic bacteria need different antibiotic treatment than hydrogen-producing bacteria.
• Failure to utilize breath testing to identify if the patient has SIBO, the type of gas he/she produces, and the overall level of gas. This information is necessary for diagnosis, treatment choice, duration, and prognosis.
• Failure to use a prokinetic immediately following treatment. Prokinetics along with diet are needed to prevent relapse of this commonly recurring condition.
• Failure to use a low-carb preventative diet following treatment. Diet along with prokinetics are needed to prevent relapse of this commonly recurring condition.
• Failure to tailor diet to individual tolerances with personal experimentation. No fixed diet can predict an individual’s complex bacterial, digestive, absorptive, immunological, and genetic circumstances; therefore customizing is necessary.
• Failure to identify underlying causative conditions. A recent report found the following conditions led to a poor response to antibiotics: anatomical abnormalities, chronic narcotic use, Addison’s disease, scleroderma, colonic inertia, inflammatory bowel disease, and NSAID-induced intestinal ulceration.69
Notes
1. Peralta S et al. Small intestine bacterial overgrowth and irritable bowel syndrome-related symptoms: experience with Rifaximin. World J Gastroenterol. 2009 Jun 7;15(21):2628–2631.
2. Lin HC et al. Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome. JAMA. 2004 Aug 18;292(7):852–858.
3. Pyleris E et al. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci. 2012 May;57(5):1321–1329.
4. Pimentel M et al. The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial. Ann Intern Med. 2006 Oct 17;145(8):557–563.
5. Lauritano EC et al. Association between hypothyroidism and small intestinal bacterial overgrowth. J Clin Endocrinol Metab. 2007 Nov;92(11):4180–4184.
6. Almeida JA et al. Lactose malabsorption in the elderly: role of small intestinal bacterial overgrowth. Scand J Gastroenterol. 2008;43(2):146–154.
7. Klaus J et al. Small intestinal bacterial overgrowth mimicking acute flare as a pitfall in patients with Crohn’s Disease. BMC Gastroenterol. 2009 Jul 30;9:61.
8. Marie I, Ducrotté P, Denis P, Menard JF, Levesque H. Small intestinal bacterial overgrowth in systemic sclerosis. Rheumatology (Oxford). 2009 Oct;48(10):1314–1319. Epub 2009 Aug 20.
9. Rubio-Tapia A et al. Prevalence of small intestine bacterial overgrowth diagnosed by quantitative culture of intestinal aspirate in celiac disease. J Clin Gastroenterol. 2009 Feb;43(2):157–161.
10. Mancilla AC et al. [Small intestine bacterial overgrowth in patients with chronic pancreatitis]. Rev Med Chil. 2008 Aug;136(8):976–980.
11. Ojetti V et al. Small bowel bacterial overgrowth and type 1 diabetes. Eur Rev Med Pharmacol Sci. 2009 Nov–Dec;13(6):419–423.
12. Goebel A et al. Altered intestinal permeability in patients with primary fibromyalgia and in patients with complex regional pain syndrome. Rheumatology (Oxford). 2008 Aug;47(8):1223–1227.
13. Gupta A et al. Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy. J Hepatol. 2010 Nov;53(5):849–855.
14. Shanab AA et al. Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8. Dig Dis Sci. 2011 May;56(5):1524–1534.
15. Weinstock LB, Klutke CG, Lin HC. Small intestinal bacterial overgrowth in patients with interstitial cystitis and gastrointestinal symptoms. Dig Dis Sci. 2008 May;53(5):1246–1251.
16. Weinstock LB, Walters AS, Restless legs syndrome is associated with irritable bowel syndrome and small intestinal bacterial overgrowth. Sleep Med. 2011 Jun;12(6):610–613.
17. Parodi A et al. Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Clin Gastroenterol Hepatol. 2008 Jul;6(7):759–764.
18. Husebye E. The patterns of small bowel motility: physiology and implications in organic disease and functional disorders. Neurogastroenterol Motil. 1999 Jun;11(3):141–161.
19. Bures J. 2010 Small intestinal bacterial overgrowth syndrome. World J Gastroenterol. 2010 Jun 28;16(24):2978–2990.
20. Pyleris E et al. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci. 2012 May;57(5):1321–1329.
21. Williams C et al. Occurrence and significance of gastric colonization during acid-inhibitory therapy. Best Pract Res Clin Gastroenterol. 2001 Jun;15(3):511–521.
22. Machado WM et al. The small bowel flora in individuals with cecoileal reflux. Arq Gastroenterol. 2008 Jul–Sep;45(3):212–218.
23. Khoshini R, Dai SC, Lezcano S, Pimentel M. A systematic review of diagnostic tests for small intestinal bacterial overgrowth. Dig Dis Sci. 2008 Jun;53(6):1443–1454.
24. Pimentel M. Gut microbes and irritable bowel syndrome [webcast]. July 20, 2012. GI Health Foundation. http://www.gihealthfoundation.org/coe/ibs/webcast/2012/july/MPimentel/?link=2012/
july/MPimentel&cme_proj_id=12&actionPage=topics/Gut_Microbes_and_
IBS/request-for-credit.cfm?cme_proj_id=12. (One link: Three lines) Accessed October 27, 2012.
25. Bouhnik Y et al. Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome. Am J Gastroenterol. 1999 May;94(5):1327–1331.
26. Youn YH, Park JS, Jahng JH, et al. Relationships among the lactulose breath test, intestinal gas volume, and gastrointestinal symptoms in patients with irritable bowel syndrome. Dig Dis Sci. 2011 Jul;56(7):2059–2066. Epub 2011 Jan 15.
27. Elsenbruch S. Abdominal pain in irritable bowel syndrome: a review of putative psychological, neural and neuro-immune mechanisms. Brain Behav Immun. 2011 Mar;25(3):386–394. Epub 2010 Nov 20.
28. Pimentel M. A New IBS Solution. Sherman Oaks, CA: Health Point Press; 2006.
29. Pimentel M, Mayer AG, Park S, Chow EJ, Hasan A, Kong Y. Methane production during lactulose breath test is associated with gastrointestinal disease presentation. Dig Dis Sci. 2003 Jan;48(1):86–92.
30. Kunkel D et al. Methane on breath testing is associated with constipation: a systematic review and meta-analysis. Dig Dis Sci. 2011 Jun;56(6):1612–1618.
31. Pimentel M, Lin HC, Enayati P, et al. Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity. Am J Physiol Gastrointest Liver Physiol. 2006 Jun;290(6):G1089–G1095. Epub 2005 Nov 17.
32. Chatterjee S et al. The degree of breath methane production in IBS correlates with the severity of constipation. Am J Gastroenterol. 2007 Apr;102(4):837–841.
33. Singh VV, Toskes PP. Small bowel bacterial overgrowth: presentation, diagnosis, and treatment. Curr Treat Options Gastroenterol. 2004 Feb;7(1):19–28.
34. DiBaise JK. Nutritional consequences of small intestinal bacterial overgrowth. Prac Gastroenterol. 2008;69:15–28.
36. Prizont R. Glycoprotein degradation in the blind loop syndrome: identification of glycosidases in jejunal contents. J Clin Invest. 1981 Feb;67(2):336–344.
37. Lauritano EC, Valenza V, Sparano L, et al. Small intestinal bacterial overgrowth and intestinal permeability. Scand J Gastroenterol. 2010 Sep;45(9):1131–1132.
38. Resnick C. Nutritional protocol for the treatment of intestinal permeability defects and related conditions. Nat Med J. March 2010.
39. Eisenmann A et al. Implementation and interpretation of hydrogen breath tests. J Breath Res. 2008 Dec;2(4):046002.
40. Quigley EM, Quera R. Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics. Gastroenterology. 2006 Feb;130(2 Suppl 1):S78–S90.
41. Quin Tron Instrument Company Inc. Quin Tron Catalog and Information. 2012:22.
42. Gottschall E. Breaking the Vicious Cycle. Baltimore, ON: Kirkton Press Ltd.; 1994.
43. Campbell-McBride N. Gut and Psychology Syndrome. Cambridge: Medinform Publishing; 2004.
44. Ong DK, Mitchell SB, Barrett JS, et al. Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome. J Gastroenterol Hepatol. 2010 Aug;25(8):1366–1373.
45. Nieves R, Jackson RT. Specific carbohydrate diet in treatment of inflammatory bowel disease. Tenn Med. 2004 Sep;97(9):407.
46. Choung RS, Ruff KC, Malhotra A, et al. Clinical predictors of small intestinal bacterial overgrowth by duodenal aspirate culture. Aliment Pharmacol Ther. 2011 May;33(9):1059–1067. doi: 10.1111/j.1365-2036.2011.04625.x. Epub 2011 Mar 13.
47. Staudacher HM, Whelan K, Irving PM, Lomer MC. Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome. J Hum Nutr Diet. 2011 Oct;24(5):487–495. doi:10.1111/j.1365-277X.2011.01162.x. Epub 2011 May 25.
48. Pimentel M, Constantino T, Kong Y, Bajwa M, Rezaei A, Park S. A 14-day elemental diet is highly effective in normalizing the lactulose breath test. Dig Dis Sci. 2004 Jan;49(1):73–77.
49. Scarpignato C, Pelosini I. Experimental and clinical pharmacology of rifaximin, a gastrointestinal selective antibiotic. Digestion. 2006;73 Suppl 1:13–27. Epub 2006 Feb 8.
50. Lombardo L, Foti M, Ruggia O, Chiecchio A. Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy. Clin Gastroenterol Hepatol. June 2010;8(6):504–508.
51. Pimentel M, Lembo A, Chey WD, et al.; TARGET Study Group. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011 Jan 6;364(1):22–32.
52. Yang J, Lee HR, Low K, Chatterjee S, Pimentel M. Rifaximin versus other antibiotics in the primary treatment and retreatment of bacterial overgrowth in IBS. Dig Dis Sci. 2008 Jan;53(1):169–74. Epub 2007 May 23.
53. Debbia EA, Maioli E, Roveta S, Marchese A. Effects of rifaximin on bacterial virulence mechanisms at supra- and sub-inhibitory concentrations. J Chemother. 2008 Apr;20(2):186–194.
54. Mencarelli A, Renga B, Palladino G, et al. Inhibition of NF-kb by a PXR-dependent pathway mediates counter-regulatory activities of rifaximin on innate immunity in intestinal epithelial cells. Eur J Pharmacol. 2011 Oct 1;668(1–2):317–324. Epub 2011 Jul 26.
55. Low K, Hwang L, Hua J, Zhu A, Morales W, Pimentel M. A combination of rifaximin and neomycin is most effective in treating irritable bowel syndrome patients with methane on lactulose breath test. J Clin Gastroenterol. 2010 Sep;44(8):547–550.
56. Logan AC, Beaulne TM. The treatment of small intestinal bacterial overgrowth with enteric-coated peppermint oil: a case report. Altern Med Rev. 2002 Oct;7(5):410–417.
57. Pimentel M, Morales W, Lezcano S, Sun-Chuan D, Low K, Yang J. Low-dose nocturnal tegaserod or erythromycin delays symptom recurrence after treatment of irritable bowel syndrome based on presumed bacterial overgrowth. Gastroenterol Hepatol (N Y). 2009 Jun;5(6):435–442.
58. Pimentel M. An evidence-based treatment algorithm for IBS based on a bacterial/SIBO hypothesis: Part 2. Am J Gastroenterol. 2010 Jun;105(6):1227–30.
59. Ploesser J, Weinstock LB, Thomas E. Low Dose Naltrexone: Side Effects and Efficacy in Gastrointestinal Disorders. International Journal of Pharmaceutical Compounding; March 2010.
60. Manabe N, Rao AS, Wong BS, Camilleri M. Emerging pharmacologic therapies for irritable bowel syndrome. Curr Gastroenterol Rep. 2010 Oct;12(5):408–16.
61. Gibson PR, Shepherd SJ. Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach. J Gastroenterol Hepatol. 2010 Feb;25(2):252–8. Review.
62. Bowman, G. The Gut, the Brain and the Functional GI Disorders. Functional Gastroenterology Seminar: Level 1. Winter 2010, p. 19.
63. Gabrielli M, Lauritano EC, Scarpellini E, Lupascu A, Ojetti V, Gasbarrini G, Silveri NG, Gasbarrini A. Bacillus clausii as a treatment of small intestinal bacterial overgrowth. Am J Gastroenterol. 2009 May;104(5):1327–8. Epub 2009 Apr 7.
64. Soifer LO, Peralta D, Dima G, Besasso H. Comparative clinical efficacy of a probiotic vs. an antibiotic in the treatment of patients with intestinal bacterial overgrowth and chronic abdominal functional distension: a pilot study. Acta Gastroenterol Latinoam. 2010 Dec;40(4):323–7.
65. Schiffrin EJ, Parlesak A, Bode C, Bode JC, van’t Hof MA, Grathwohl D, Guigoz Y. Probiotic yogurt in the elderly with intestinal bacterial overgrowth: endotoxaemia and innate immune functions. Br J Nutr. 2009 Apr;101(7):961–6.
66. Ruland J. Return to homeostasis: downregulation of NF-κB responses. Nat Immunol. 2011 Jun 19;12(8):709–14. doi: 10.1038/ni.2055.
67. Al-Sadi RM, Ma TY. IL-1beta causes an increase in intestinal epithelial tight junction permeability. J Immunol. 2007 Apr 1;178(7):4641–9.
68. Csaki C, Mobasheri A, Shakibaei M. Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1beta-induced NF-kappaB-mediated inflammation and apoptosis. Arthritis Res Ther. 2009;11(6):R165. Epub 2009 Nov 4.
69. Chou J, Tabrizi R, Pimentel M, Sokol T. S1326 Presumed IBS Subjects With Short Remission After Antibiotic Therapy Often Have Secondary Causes for Their Symptoms. Gastroenterology, Volume 138, Issue 5, Supplement 1 , Pages S–229, May 2010.
Allison Siebecker, ND, MSOM, LAc
Steven Sandberg-Lewis, ND, DHANP
NCNM Clinic
3025 SW Corbett Ave.
Portland, Oregon 97211
Allison Siebecker, ND, MSOM, LAc, is a graduate of NCNM, where she specializes in treating SIBO in her private practice. She is the author of an educational website on SIBO, is currently writing a book on SIBO, and teaches continuing education to physicians on SIBO and related topics. In 2005, Dr. Siebecker received the Best in Naturopathy award from the Townsend Letter for her article “Traditional Bone Broth in Modern Health and Disease.” Visit her educational website at www.siboinfo.com.
Steven Sandberg-Lewis, ND, DHANP, is a graduate of NCNM, where he practices, supervises student shifts, and has been professor of gastroenterology since 1996. In 2009, Dr Sandberg-Lewis received the Best in Naturopathy award from the Townsend Letter for his article “Hiatal Hernia Syndrome” and honorable mention in 2011 for his article “Proton Pump Inhibitors – A Risky Experiment?” His textbook, Functional Gastroenterology, is available at www.ncnm.edu/bookstore.