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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 (Peralta S, 2009) and as high as 84% in one study using breath testing as the diagnostic marker (Lin HC, 2004.) It accounts for 37% of cases when endoscopic cultures of aerobic bacteria are used for diagnosis (Pyleris E, 2012.) Eradication of this overgrowth leads to a 75% reduction in IBS symptoms (Pimentel M, 2003). 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
• Abdominal pain, cramps
• Constipation, diarrhea or alternation between the two
• Heartburn
• Nausea
• Malabsorption - steatorrhea, anemia
• Systemic symptoms - headache, joint pain, fatigue, rosacea
• Other diseases associated with SIBO include hypothyroidism (Lauritano EC, 2007), lactose intolerance (Almeida JA, 2008), Crohns disease (Klaus J, 2009), systemic sclerosis (Marie I, 2009), celiac disease (Rubio-Tapia A 2009), chronic pancreatitis (Mancilla AC, 2008), diabetes with autonomic neuropathy (Ojetti V, 2009), fibromyalgia and chronic regional pain syndrome (Goebel A, 2008), hepatic encephalopathy (Gupta A, 2010), non-alcoholic steatohepatitis (Shanab AA, 2011), interstitial cystitis (Weinstock LB, 2007), restless leg syndrome (Weinstock ,LB, 2011) and acne rosacea (Parodi A, 2008.)
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 (Husebye E, 1999) because stasis promotes bacterial growth. Also key in prevention is gastric and pancreatic secretion (Bures J, 2010.) The use of proton pump inhibitors encourages overgrowth, especially of the hydrogen producing type (Pyleris E, 2012). We also suspect an important role for proper ileocecal valve function in preventing reflux of colonic bacteria into the small intestine (Machado WM, 2008.) Proper bile salt secretion may also be protective and there is evidence that SIBO can cause bile acid deconjugation leading to fat malabsorption (Williams C, 2001.)
How SIBO causes the symptoms of IBS
≥ 105 colony-forming units (CFU)] per mL of proximal jejunal aspiration is the definition of SIBO in culturing studies. The bacteria which are most commonly overgrown are both anaerobes (Bacteroides 39%, Lactobacillus 25%, Clostridium 20%) and aerobes (Streptococcus 60%, Escherichia coli 36%, Staphylococcus 13%, Klebsiella 11%) (Bouhnik Y, 1999), (Escherichia coli 37%, Enterococcus spp 32%, Klebsiella pneumonia 24%, Proteus mirabilis 6.5%) (Pyleris E, 2012).
Bloating is caused by bacterial production of hydrogen and/or methane gas. This leads to distention, pain, eructation and flatulence. The quantity of gas may be extensive, causing distention and abdominal pain. The gases also affect motility with hydrogen typically leading to diarrhea (Pimentel M, 2003) and methane causing constipation (Kunkel D, 2011.) The volume of the methane overproduction correlates with the severity of constipation (Chatterjee S, 2007.) Macrocytic anemia and iron deficiency without anemia (low ferritin level) are caused by bacterial uptake of B12/ iron or diarrhea induced malabsorption (DiBaise JK, 2008, Alonso Cotoner C, 2003 and personal clinical experience.)
Treatment of SIBO
In 2006, Dr Pimentel shared his treatment algorithm for IBS with SIBO which included the use of either antibiotics, elemental diet or both (Pimentel, 2006). Our approach offers two additional options: diet and herbal antibiotics (figure 1).
Diet
We advise diet (Specific Carbohydrate Diet or Gut and Psychology Syndrome Diet) for all SIBO patients (Gottschall E, 1994) (Campbell-McBride N, 2004). 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. Reducing carbohydrates may also reduce the overall bacterial load as the food supply shrinks, though formal studies to validate this are lacking. Many patients experience a rapid and significant decrease in symptoms after starting a SIBO diet. These diets decrease polysaccharides, oligosaccharides and disaccharides by eliminating grains, starchy vegetables, lactose, sweeteners other than honey, and in the beginning, beans. The Specific Carbohydrate Diet has been reported to have an 84% success rate for Inflammatory Bowel Disease (Nieves & Jackson, 2004). Diet alone has proven successful for infants and children, but for adults one or more of the other three treatment options are often needed, particularly in cases when diet needs to be very restricted to obtain symptomatic relief. 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 pre-digested 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 2-3 weeks, and has a success rate of 80-85% (Pimentel 2004). 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 non-absorbable. Its non-absorbability 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 (Scarpignato C, 2006). Rifaximin has up to a 91% success rate (Lombardo L, 2010) and is given at 550mg tid x 14 days (Pimentel M, 2011). Additionally, rifaximin has several unique benefits: it does not cause yeast overgrowth (Scarpignato C, 2006), it decreases antibiotic resistance in bacteria by reducing plasmids (Debbia EA, 2008), antibiotic resistance does not develop to it making it effective for re-treatments (Yang J, 2008), and it is anti-inflammatory, decreasing intestinal inflammatory cytokines and inhibiting NF- Κβ via the PXR gene (Mencarielli A, 2011). Rifaximin is best used for SIBO when hydrogen is present but when methane gas is present, double therapy of rifaximin plus neomycin (500mg bid) is more effective (Low K, 2009). Many gastroenterologists use metronidazole (250mg tid) 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 (Logan A, 2002), our experience is that they have similar effectiveness to antibiotics. We have used the following botanicals: Allium sativum, Hydrastis canadensis and other berberine containing herbs, Origanum vulgare, cinnamomum spp., 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 x 30 days. Specific single dosages we have used include allicin extract of garlic: 450mg bid-tid, goldenseal /berberine: 5g qd in split dosage, emulsified oregano: 100mg bid and neem: 300mg tid. Our breath testing has validated the need for the longer treatment period of 30 days for herbal antibiotics compared to 14 days for antibiotics. We have also observed prolonged die off reactions with this method 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
SIBO is a disease that relapses because eradication itself, does not always correct the underlying cause (Pimentel M, 2009, 2010). 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 1). 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 (Pimentel M, 2009). Prokinetics stimulate the MMC, symptomatically correcting this underlying cause. Prokinetics studied for SIBO include: low dose naltrexone 2.5mg qd-bid hs (Ploesser J, 2010), low dose erythromycin 50mg hs, and tegaserod 2-6mg hs (Pimentel M, 2009). Tegaserod has a higher success rate for SIBO prevention versus erythromycin (Pimentel M, 2009), but has been withdrawn from the US for safety reasons. Prucalopride 1-4mg hs, is not yet available in the US but is a safer alternative to Tegaserod (Manabe N, 2010). A trial removal of the prokinetic at ≥ 3 months is suggested but continued long term use may be needed (Pimentel M, 2006).
A lower carbohydrate diet is used in combination with a prokinetic to discourage a return of bacterial overgrowth by limiting the food they thrive on. Once the overgrowth is gone and small intestine damage has healed, the diet can be expanded beyond the strictness of the Specific Carbohydrate and Gut and Psychology Syndrome Diets. At this point, the Cedars-Sinai Diet (Pimentel M, 2006), Fodmap Diet (Gibson PR, 2010) or a similar lower carb diet may be adopted long term, as the patient tolerates.
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 1).
· 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 they produce, 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 (Chou J, 2010).
References:
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):2628-31.
Lin HC, et al. Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome. JAMA. 2004 Aug 18;292(7):852-8.
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):1321-9.
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):557-63.
Lauritano EC et al, Association between hypothyroidism and small intestinal bacterial overgrowth. J Clin Endocrinol Metab. 2007 Nov;92(11):4180-4.
Almeida JA et al, Lactose malabsorption in the elderly: role of small intestinal bacterial overgrowth. Scand J Gastroenterol. 2008;43(2):146-54.
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.
Marie I et al, Small intestinal bacterial overgrowth in systemic sclerosis. Rheumatology (Oxford). 2009 Oct;48(10):1314-9.
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):157-61.
Mancilla A C et al, [Small intestine bacterial overgrowth in patients with chronic pancreatitis]. Rev Med Chil. 2008 Aug;136(8):976-80.
Ojetti V et al, Small bowel bacterial overgrowth and type 1 diabetes. Eur Rev Med Pharmacol Sci. 2009 Nov-Dec;13(6):419-23.
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):1223-7.
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):849-55.
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):1524-34.
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):1246-51.
Weinstock LB, Walters AS, Restless legs syndrome is associated with irritable bowel syndrome and small intestinal bacterial overgrowth. Sleep Med. 2011 Jun;12(6):610-3.
Parodi A et al, Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Clin Gastroenterol Hepatol. 2008 Jul;6(7):759-64.
Husebye E, The patterns of small bowel motility: physiology and implications in organic disease and functional disorders. Neurogastroenterol Motil. 1999 Jun;11(3):141-61.
Bures J, 2010 Small intestinal bacterial overgrowth syndrome. World J Gastroenterol. 2010 Jun 28;16(24):2978-90.
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):1321-9.
Machado WM et al, The small bowel flora in individuals with cecoileal reflux. Arq Gastroenterol. 2008 Jul-Sep;45(3):212-8.
Williams C et al, Occurrence and significance of gastric colonization during acid-inhibitory therapy. Best Pract Res Clin Gastroenterol. 2001 Jun;15(3):511-21.
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):1327-31.
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):1321-9.
Pimentel M, Kong Y, Park S, Breath testing to evaluate lactose intolerance in irritable bowel syndrome correlates with lactulose testing and may not reflect true lactose malabsorption. Am J Gastroenterol. 2003 Dec;98(12):2700-4.
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):1612-8.
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):837-41.
DiBaise JK. Nutritional consequences of small intestinal bacterial overgrowth. Prac Gastroenterol. 2008;69:15-28.
Alonso Cotoner C et al, [Iron deficiency: not always blood losses]. An Med Interna. 2003 May;20(5):227-31.
Pimentel, M. A New IBS Solution. Health Point Press, Sherman Oaks, Ca. 2006. p. 90.
Gottschall E. Breaking the Vicious Cycle. Kirkton Press Ltd, Baltimore Ontario Canada, 1994.
Campbell-McBride N. Gut and Psychology Syndrome. Medinform Publishing, Cambridge UK, 2004.
Nieves R, Jackson RT. Specific carbohydrate diet in treatment of inflammatory bowel disease. Tenn Med. 2004 Sep;97(9):407.
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):73-7.
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.
Lombardo L, Foti M, Ruggia O, Chiecchio A. Increased Incidence of Small Intestinal Bacterial Overgrowth During Proton Pump Inhibitor Therapy. Clinical Gastroenterology and Hepatology
Volume 8, Issue 6 , Pages 504-508, June 2010.
Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP; TARGET Study Group. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011 Jan 6;364(1):22-32.
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.
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):186-94.
Mencarelli A, Renga B, Palladino G, Claudio D, Ricci P, Distrutti E, Barbanti M, Baldelli F, Fiorucci S. Inhibition of NF-κB 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):317-24. Epub 2011 Jul 26.
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):547-50.
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):410-7.
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):435-42.
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.
Ploesser J, Weinstock LB, Thomas E. Low Dose Naltrexone: Side Effects and Efficacy in Gastrointestinal Disorders. International Journal of Pharmaceutical Compounding; March 2010.
Manabe N, Rao AS, Wong BS, Camilleri M. Emerging pharmacologic therapies for irritable bowel syndrome. Curr Gastroenterol Rep. 2010 Oct;12(5):408-16.
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.
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.Top of Form
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