Small Intestinal Bacterial Overgrowth. Lela Altman, ND, EAMP Adjunct Faculty and Clinical Supervisor at the Bastyr Center for Natural Health

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1 Small Intestinal Bacterial Overgrowth Lela Altman, ND, EAMP Adjunct Faculty and Clinical Supervisor at the Bastyr Center for Natural Health

2 Acknowledgements Special thanks to Eric Schoen (ND Candidate), Tom Yang, ND, Kelly Morrow, RD and Eric Yarnell, ND, RH(AHG) for their contributions to this presentation.

3 What is SIBO? Small intestinal bacterial overgrowth (SIBO) is a condition in which non-native bacteria and/or native bacteria are present in increased numbers resulting in excessive fermentation, inflammation, and/or malabsorption. 1 In other words, there are too many bacteria or the wrong type of bacterial where there shouldn t be.

4 Signs of SIBO Bloating Diarrhea Constipation Flatulence Abdominal pain Indigestion Weight loss/gain Malabsorption Malnutrition Anemia Dyspepsia/reflux May be asymptomatic Symptoms similar to IBS

5 IBS Irritable Bowel Syndrome is a gastrointestinal syndrome characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause. Has many similar signs and symptoms as SIBO

6 IBS Affects about 10-15% of the population in North America 2-7 Only 15% of persons with IBS seek medical attention 8-10 Still, this accounts for 25-50% of all referrals to gastroenterologists 11 Second highest cause of missed work after the common cold 12 Accounts for roughly $30 billion in health care dollars each year 13

7 60-80% of all IBS is actually 14 SIBO

8 How do our bodies naturally prevent against SIBO? 17 Stomach acid Intestinal Motility Ileocecal valve Gut immune system Digestive secretions (bacteriocidal)

9 What are the causes of SIBO? 17 Predisposing Conditions Chronic pancreatitis (SIBO in up to 40%) Immunodeficiency (IgA deficiency, AIDS) Low stomach acid (SIBO increased w/ long term PPI use) Liver cirrhosis Scleroderma Motility Disorders/Slow bowels Joint hypermobiliy syndromes (Ehlers Danlos, Marfans) Anatomical/Structural abnormalities (obstructions, diverticula, fistulae, gastric bypass, removal of IC valve, intrabdominal adhesions, blind loops) Elderly 17, 18 (present in up to 90% of yo) Food poisoning (more on this later)

10 What are the causes of SIBO? Medications Opioids Chronic antibiotic use Acid blocking medications Long term corticosteroid use Anti-diarrheals

11 How is Food Poisoning related to SIBO? 16 Autoimmune/Post-Infectious Etiology of SIBO Food poisoning from bacterial pathogens such as Campylobacter jejuni, Shigella, E.coli, and Salmonella These pathogens create cytolethal distending toxin-b, or Cdt-B. Cdt-B is structurally similar to a protein in our intestines called vinculin, which is responsible for normal small intestine motility. Upon exposure to Cdt-B, a an individuals immune system will be triggered to produce antibodies against Cdt-B. Due to molecular mimicry, these anti-cdt-b antibodies attack and destroy both Cdt-B and vinculin, thus decreasing gut motility and decreasing migrating motor complex (MMC) MMC triggers a wave of motility that cleans the small intestine by moving bacteria into the large intestine during the fasting state After one recovers from food poisoning, these antibodies remain in their body increasing their risk of developing SIBO again and often necessitating the use of a prokinetic.

12 How is Food Poisoning related to SIBO? 16

13 What other conditions are associated with SIBO? Diabetes (gastroparesis) Parkinson's Disease (54% have SIBO 15 ) Osteoporosis Anemia Celiac disease Crohn s disease Ulcerative Colitis Chronic Liver disease Fibromyalgia Rosacea Cystic fibrosis

14 What are the complications of SIBO? Production of toxins (ammonia, D-lactic acidosis, gram negative endotoxins) This can lead to neurological symptoms Production of gasses can cause loose stools or constipation, abdominal distention and flatulence. Decreased absorption of vitamins Neuropathy from B-12 deficiency, Anemia from B-12, folate or iron deficiency Fat, carbohydrate, and protein malabsorption leading to weight loss and other problems

15 Diagnosis How can one be tested for SIBO? Jejunal Aspirate SIBO Breath test

16 Diagnosis-Jejunal Aspirate Gold Standard Demonstrated by excessive bacterial concentrations in jejunal aspirates (>10 5 CFU/mL of colon flora best defines SIBO, but SIBO can be patchy and missed by aspirate)

17 Diagnosis-Jejunal aspirate Drawbacks Few of the gut bacteria can be identified because most species of bacteria in the gut cannot be cultured Culture of anaerobic organisms is difficult (technique) Contamination from oropharangeal flora Bacterial overgrowth can be patchy and may be missed or inaccessible Invasive and expensive

18 Diagnosis-Breath tests In healthy individuals, intestinal gas forms from swallowed air and from bacterial fermentation of food in the colon. There are normal peaks of gas released with bacterial action in the colon. In SIBO, gut microbes expand proximally into the small intestine instead of being confined predominantly to the colon so there will be gas formation in the small intestine as well. We can use the breath tests to look for methane and hydrogen peaks in the small intestine. Unfortunately, they do not detect hydrogen sulfide which is also produced by some bacteria. Early peaks indicate the presence of small intestinal overgrowth

19 Diagnosis-Breath tests Sensitivity and specificity of breath tests varies dramatically depending on different studies and types of sugars used for the test. Sensitivity and specificity ranging from 27% 98% and 36% 100% respectively, depending on study. Less invasive and expensive than jejunal aspirate. Safe-can be done on children and women of child bearing age. Protocols are not standardized so beware comparisons between labs Different sugars such as lactulose or glucose may be used

20 Hydrogen vs. Methane Human cells do not produce either of these gasses. They are produced by microbes. Hydrogen Produced by bacteria Typically associated with diarrhea Methane Produced by archaea (single celled prokaryotes, differs from bacteria in cell wall composition) Typically associated with constipation Generally considered harder to treat. Lower threshold needed to consider positive

21 Treatment First, find and treat the underlying cause of SIBO (if possible) Three Phases 1. Antimicrobial Phase 2. Pro-Kinetic Phase (not always necessary) 3. Maintenance Phase (not always necessary)

22 Herbal Antimicrobials Antibiotics Elemental Diet Antimicrobial Phase Low FODMAP or other diets (for treatment and maintenance)

23 Herbal Therapy Many antimicrobial herbs available individually or in combinations. Duration: 6-8 Weeks Cost: Approximately $100-$200/month Cons: Can take several weeks to months and usually requires strict diet adherence Efficacy: highly variable

24 Herbal Therapy Allicin (not garlic powder) 450mg TID Oregano Oil 50mg TID Neem (available at 300mg capsule) 500mg TID Berberine (as Berberine HCl) mg TID There are also many other combination products available commercially. Be careful with anti-parasitic herbs. SE: Nausea esp. at higher dose, decreases blood sugar

25 Natural Antimicrobials Allium sativum (but gut flora have evolved resistance) Plant volatile oils (Origanum, Thymus, etc.): also high resistance (Emiroğlu 2010) The reason we use natural antimicrobials normally is that they don t damage normal flora or healthy cells! Combinations of multiple high-dose agents? Completely theoretical at this point

26 Antibiotic Therapy Preference is given to antibiotics that are poorly absorbed (i.e. stay in the gut). If methane is present on the breath test, 2 antibiotics may need to be used together. Duration: 2 weeks Cost: depends on insurance coverage, ranges from $15 - $1200 Cons: potential side effects Efficacy: 40-80% depending on antibiotic used, strength, duration and study May require repeated treatments to clear infection

Minimally absorbed Rifaximin Inhibits DNA-dependent RNA polymerase Dose: 400 550 mg tid x 10 d Problems: expensive Alternative: neomycin 500 mg bid;

27 Minimally absorbed Rifaximin Inhibits DNA-dependent RNA polymerase Dose: mg tid x 10 d Problems: expensive Alternative: neomycin 500 mg bid; metronidazole 250 mg tid (inferior and more toxic vs rifaximin: Lauritano 2009) Also useful for traveler s diarrhea, Gram negative diarrhea Overall review (Koo 2010)

28 Rifaximin Adjuncts Partially-hydrolyzed guar gum 5 g added to rifaximin enhances its efficacy (Furnari 2010) Probiotics: not necessarily recommended, as you are potentially pouring in more of the microbes that are already in the wrong place Prokinetics: probably to treat underlying gut motility issues

29 Elemental Diet Liquid diet-there are home-made versions and pre-packaged versions Duration: 2-3 Weeks Cost: $250-$900 depending on type used Cons: grueling diet, nausea Efficacy: 80-85%

30 Prokinetic Phase Prokinetics increase motility of the small intestine to keep bacteria from backing-up into the small intestine. Both herbal and pharmaceutical options are available. Typical duration is 4-6 months minimum

31 Prokinetics Fasting between meals and at night Diets Maintenance Phase

32 What diets can be helpful for SIBO? Low FODMAPs Diet Specific Carbohydrate diet The SIBO diet Cedars-Sinai diet GAPS diet

33 Duration of Dietary Treatment Highly variable from person to person Depends on where the person is at in their treatment Before diagnosis Diet modification for symptom control Active treatment Can sometimes eat more liberally Diet based on symptoms Post treatment Important to eat lower carbohydrate / low FODMAP for several months to prevent recurrence SLOW transition back to normal eating

34 CITATIONS 1) Pimental, Mark et al. Clinical manifestations and diagnosis of small intestinal bacterial overgrowth UpToDate. 25 January October 2016 < 2) Talley NJ, Zinsmeister AR, Van dyke C, Melton LJ. Epidemiology of colonic symptoms and the irritable bowel syndrome. Gastroenterology. 1991;101(4): ) Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci. 1993;38(9): ) Brandt LJ, Chey WD, Foxx-orenstein AE, et al. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol. 2009;104 Suppl 1:S ) Hahn BA, Saunders WB, Maier WC. Differences between individuals with self-reported irritable bowel syndrome (IBS) and IBS-like symptoms. Dig Dis Sci. 1997;42(12): ) Saito YA, Locke GR, Talley NJ, Zinsmeister AR, Fett SL, Melton LJ. A comparison of the Rome and Manning criteria for case identification in epidemiological investigations of irritable bowel syndrome. Am J Gastroenterol. 2000;95(10): ) Thompson WG, Irvine EJ, Pare P, Ferrazzi S, Rance L. Functional gastrointestinal disorders in Canada: first population-based survey using Rome II criteria with suggestions for improving the questionnaire. Dig Dis Sci. 2002;47(1): ) Jones R, Lydeard S. Irritable bowel syndrome in the general population. BMJ. 1992;304(6819): ) Heaton KW, O'donnell LJ, Braddon FE, Mountford RA, Hughes AO, Cripps PJ. Symptoms of irritable bowel syndrome in a British urban community: consulters and nonconsulters. Gastroenterology. 1992;102(6):

35 10) Ford AC, Forman D, Bailey AG, Axon AT, Moayyedi P. Irritable bowel syndrome: a 10-yr natural history of symptoms and factors that influence consultation behavior. Am J Gastroenterol. 2008;103(5): ) Everhart JE, Renault PF. Irritable bowel syndrome in office-based practice in the United States. Gastroenterology. 1991;100(4): ) Schuster MM. Diagnostic evaluation of the irritable bowel syndrome. Gastroenterol Clin North Am. 1991;20(2): ) Sandler RS, Everhart JE, Donowitz M, et al. The burden of selected digestive diseases in the United States. Gastroenterology. 2002;122(5): ) Dukowicz AC, Lacy BE, Levine GM. Small intestinal bacterial overgrowth: a comprehensive review. Gastroenterol Hepatol (N Y). 2007;3(2): ) Fasano A, Bove F, Gabrielli M, et al. The role of small intestinal bacterial overgrowth in Parkinson s disease. Mov Disord. 2013;28(9): ) Pimental M, Morales W, Brikos C, et al. Autoimmunity Links Vinculin to the Pathophysiology of Chronic Functional Bowel Changes Following Campylobacter jejuni Infection in a Rat Model. Dig Dis Sci May;60(5): ) Bures J, Cyrany J, Kohoutova A, et al. Small intestinal bacterial overgrowth syndrome. World J Gastroenterol. 2010; 16(24): ) Almeida JA, Kim R, Stoita A, McIver CJ, Kurtovic J, Rior-dan SM. Lactose malabsorption in the elderly: role of small intestinal bacterial overgrowth. Scand J Gastroenterol2008; 43:

SIBO

SIBO SIBO What is it? Small Intestinal Bowel Overgrowth A chronic bacterial infection of the small intestine Caused by bad bacteria such as E Coli and Clostridium migrating to the small intestine There is not