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Best of Naturopathic Medicine 2013 Page 1, 2, 3, 4 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 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 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). 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. Page 1, 2, 3, 4