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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 builds and distributes the Breathtracker, which is used to measure these gases following a 24- to 48-hour prep diet and an overnight fast. After collection of the 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. Lactulose is a disaccharide solution of galactose and fructose in a base which also contains a minute quantity of lactose and epilactose.69 Transit time for lactulose through the stomach and small bowel is approximately 120 minutes. 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.70 Serial breath specimens are taken every 20 minutes during this time and for a third hour as well. Breath may be sampled and immediately analyzed at a lab, or these samples may be acquired at home using a series of tubes and a transfer device for later analysis. Home breath samples are exhaled into special vials similar to a Vacutainer tube, which store the labeled sample until it can be delivered to the lab. Not all labs have the equipment to test for methane, and the methodology for hydrogen sulfide is currently being perfected and is therefore not yet available. Testing for methane in addition to hydrogen is important because treatment varies based on the type of gas. The unique symptom of H2S production is "rotten egg" odor to the belching or flatus.
Preparation for the test varies from lab to lab, but a typical prep diet is limited to white rice, fish/poultry/meat, eggs, hard cheeses, 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 lactulose solution by eliminating fermentable foods the day prior to testing. In cases of constipation, 2 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, although some sources recommend 4 weeks.71 If symptoms allow, proton pump inhibitors should also be eliminated for at least seven days before testing.72
Interpretation of the test varies among practitioners. The criteria provided by Quintron 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.
Additional testing and interpretation parameters:
- Hydrogen sulfide SIBO may be suspected when the typical symptoms are present but the breath test shows "flat-line" hydrogen and methane levels.73
- Modest levels of methane gas at any level equal or greater than 3 ppm at any sample on a 3-hour lactulose breath test may be a cause of methane-induced constipation.74
- A "spot methane" level may be used for follow-up testing in methane-positive individuals. When testing methane alone, there is no need for a preparatory diet or fasting prior to this single breath sample.
IBS subjects who have elevated breath methane are constipated in most cases. In murine studies, methane infusion prolonged intestinal transit time.75
We have found that an absolute level of gases, 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 which remains elevated for the duration of the test. In cases such as these, methane may only rise a few ppm over baseline, but the level is consistently above positive. Interpretation of elevated hydrogen or methane on the baseline specimen (pre-lactulose ingestion) is controversial, but at the SIBO Center we prefer to consider a high baseline methane to be a positive test.76
The classic positive for SIBO has been considered to be a double peak, with the first peak representing the small intestine and the second peak representing the normal large intestine bacteria. It is not essential to have a second peak in order to have an accurate test. We find that a single peak which rises highest in the third hour may also represent distal SIBO followed by the normal colonic gas levels.
Breath testing may be used in pediatric cases, so long as the child can follow instructions to collect the samples. 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 1 g/kg body weight with a maximum of 10 g (22 pounds and above receive the max/adult dose of 10 g).77 Lactulose is available only by prescription.
Treatment of SIBO
In 2006, Pimentel shared his treatment algorithm for SIBO, which included the use of antibiotics, elemental diet or both.78 Our approach offers two additional options: diet and herbal antibiotics.
Figure 4: SIBO Treatment Protocol (pdf)
Diet
We advise the use of the Specific Carbohydrate Diet or the SIBO Specific Diet.79,80 The latter (see www.siboinfo.com/diet.html) is a combination of the Specific Carbohydrate Diet, the low-FODMAP diet, and the clinical experience of Siebecker in the treatment of SIBO with diet. Bacteria use carbohydrates as their energy source and ferment them to gases; therefore, a low-carbohydrate diet can directly reduce symptoms by decreasing the amount of gas produced.81 Reducing carbohydrates may also decrease the overall microbial load, though formal studies to validate this are lacking. The Specific Carbohydrate Diet and the SIBO Specific Diet greatly reduce the intake of polysaccharides, oligosaccharides, and disaccharides by eliminating all grains, starchy vegetables, lactose, and sweeteners other than honey or dextrose. Legumes are often avoided in initial phases of these diets. Many patients experience a rapid and significant decrease in symptoms after starting a SIBO diet. The Specific Carbohydrate Diet has been reported to have an 84% success rate for inflammatory bowel disease, a condition commonly associated with SIBO.82,83 Patients who find the Specific Carbohydrate Diet or SIBO Specific Diet approach too restrictive can follow the Cedars-Sinai diet as described at www.gidoctor.net/diet-ibs-sibo.php.
The low-FODMAP diet is a nutritional plan that greatly reduces the fermentable levels of carbohydrate-containing foods and has a success rate of 76% in IBS.84, 85 The low-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 helpful in SIBO because these carbohydrates – which normally feed the host – also feed the increased numbers of microflora in the small intestine (Figure 2).
Diet alone has proved successful for infants and younger children, but for older children and adults, one or more of several treatment options are often needed to reduce bacteria quickly, particularly in cases in which the patient's diet becomes excessively limited in an attempt to obtain symptomatic relief. Additionally, any of the diets discussed above need to be customized to the individual by trial and error over time.
Low-carbohydrate diets often induce weight loss. Particular attention must be paid to underweight patients. Increased intake of winter squash, glucose, or honey may be recommended in these circumstances. White rice (jasmine/sticky variety is best) or white potato may also be needed to maintain weight along with medium-chain triglyceride sources such as coconut and other oils.
Diet is also essential for prevention of relapse following successful SIBO eradication. Pimentel recommends postponing any dietary changes until after the effective treatment of the microbial overgrowth, rather than during the treatment phase.86 Our clinical experience with the SIBO Specific Diet is that it is beneficial for both the treatment and prevention phases.
Elemental Diet
An elemental diet can be used in place of antibiotics or herbal antibiotics to rapidly decrease bacteria. In the treatment of SIBO, elemental diet is used to the exclusion of all other food sources. These products are a powdered mix of free-form amino acids, fat, vitamins, and minerals as well as rapidly absorbed carbohydrates. The concept behind this treatment is that the nutrients will be absorbed before reaching the involved organisms, thus feeding the patient but starving the flora. It is used in place of all meals, for 2 to 3 weeks, and has a success rate of 80% to 85% using the Nestlé product Vivonex Plus.87 Two versions of a homemade recipe for elemental diet can be found at www.siboinfo.com/elemental-formula.html. Elemental diets are not protein powders or typical detoxification formulas. They are available over the counter and are not reimbursed by most insurance coverage, which can make this treatment costly. Patients should be warned that Vivonex Plus or homemade elemental diets are very bitter tasting. Elemental diets may not be suitable to underweight patients who cannot afford to lose weight.
Herbal Antibiotics
While there have only been two published reports of herbal antibiotics in the treatment of SIBO, our experience is that they have similar effectiveness to antibiotics.88,89 Chedid et al. studied patients with SIBO based on a positive lactulose breath test. A negative breath test after treatment was seen in 34% of the rifaximin- or triple-antibiotic-treated group vs. 46% of the herbal-treated group.
The study employed a pair of herbal formulas. The dosage was 2 capsules of each b.i.d. for 30 days. The two different paired formulas are listed in Table 1 below (FC-Cidal plus Dysbiocide or Candibactin-AR plus Candibactin-BR):
Table 1: Herbal Preparations for the Treatment of Small Intestine Bacterial Overgrowth (pdf)
At our center we have used the following botanicals: Allium sativum (garlic), Hydrastis canadensis and other berberine-containing herbs, Origanum vulgare (oregano), and Azadirachta indica (neem). 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 that we have used include allicin extract of garlic: 450 mg b.i.d.-t.i.d., goldenseal/berberine: 5 g q.d. in divided dosage, emulsified oregano: 100 mg b.i.d. and a formula that contains 300 mg of neem plus a proprietary blend containing a total of 200 mg of the following: Emblica officinalis, Terminalia chebula, Terminalia belerica, Tinospora cordifolia, and Rubia cordifolia. The latter formula is dosed at 1 capsule t.i.d. Researchers at Johns Hopkins have studied other herbal combinations that are listed in Table 1. Our breath testing has validated the need for the longer treatment period of 30 days for herbal antibiotics compared with 14 days for prescription antibiotics. Note that although whole garlic is a high-FODMAP food, we do not observe purified allicin to provoke symptoms in our patients. Allicin is the only herb which we have noted so far that can reduce breath methane levels. We have also observed that some patients experience prolonged die-off reactions with herbal treatment that can last for the duration of the treatment course. More studies on herbal antibiotics for SIBO are needed, particularly to identify botanicals effective in reducing methane.
Antibiotics
The most studied and successful prescription antibiotic for SIBO is rifaximin (brand name Xifaxan). It has a broad spectrum of activity and is nonabsorbable. Its luminal status allows it to act locally, and it is therefore less likely to cause systemic side effects common to other antibiotics.90 Rifaximin has up to a 91% success rate and is given at 550 mg t.i.d. × 14 days.91,92 Many physicians continue to prescribe a lower dosage of 1200 mg b.i.d. × 10 days, although research shows a 22% increase in breath test normalization with the higher dosage. Suggested pediatric dosages are 200 mg t.i.d. × 7 days for ages 3 to 15 or 10 to 30 mg/kg.93,94
Additionally, rifaximin has several unique benefits: it purportedly does not cause yeast overgrowth and it decreases antibiotic resistance in bacteria by reducing plasmids.95,96 Antibiotic resistance does not develop to rifaximin, making it effective for retreatments, and it has anti-inflammatory properties, decreasing intestinal inflammatory cytokines and inhibiting NF-kb via the PXR gene.97,98 Rifaximin as a solo antibiotic is best used for SIBO when only the hydrogen levels are elevated. When methane gas is also increased, double therapy of rifaximin plus neomycin (500 mg b.i.d. × 14 days) is more effective.99 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.
Furnari et al. compared the percentage of breath test normalization using rifaximin 1200 mg q.d. vs. rifaximin 1200 mg q.d. plus partially hydrolysed guar gum (5 g q.d.) for 10 days. The combination treatment was proved to be 23% more effective than rifaximin monotherapy.100
If hydrogen sulfide SIBO is suspected the same treatments as those used for methanogen overgrowth are indicated.
Biofilm Disruptors
Mucosal methanogenic organisms can elaborate biofilms.101 The use of N-acetylcysteine, nattokinase, serrapeptase, or lumbrokinase may be considered in addition to herbal or prescription antibiotic treatment to provide mucolytic and biofilm disruption effects. As mentioned earlier in this article, there is evidence both for and against enteric mucosal biofilms and SIBO.
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