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SIBO is a disease that relapses because eradication itself does not always correct the underlying cause.102,103 Pimentel's 2006 treatment algorithm includes 2 essential preventions: diet and a prokinetic (motility agent). Our approach offers additional options: hydrochloric acid, probiotics, and brush border healing supplements. Also worth consideration are physical exercises, breathing techniques, acetylcholine precursors and modulators of neural inflammation.
A key underlying cause of SIBO is thought to be deficient activity of the migrating motor complex (MMC). An intact MMC moves debris and bacteria down into the large intestine during fasting at night and between meals.104 Prokinetics stimulate the MMC, symptomatically correcting this underlying cause. Iberogast is a German compound botanical tincture with possible prokinetic action.105 This formula includes alcoholic extracts of Iberis amara totalis recens, Angelicae radix, Cardui mariae fructus, Chelidonii herba, Liquiritiae radix, Matricariae flos, Melissae folium, Carvi fructus, and Menthae piperitae folium. It has been used to treat functional dyspepsia and IBS since the 1960s. One study found symptom improvement, but no increase in gastric emptying, which suggests that if this formula is prokinetic, it is likely not the only mechanism underlying its action in IBS.106 A double-blind controlled trial compared Iberogast with cisapride (a prescription prokinetic with limited special use in the US due to cardiovascular side effects). The herbal formula performed as well as the prokinetic drug for functional dyspepsia and was superior to metoclopramide in a retrospective cohort study of 961 patients.107,108 It has also been shown to be effective for IBS in children.109,110
Prescription prokinetics studied for SIBO include low dose naltrexone 2.5 mg q.h.s. for IBS-D or 2.5 mg b.i.d. for IBS-C, low-dose erythromycin 50 mg q.h.s., and tegaserod 2 to 6 mg q.h.s.112,111 Tegaserod has a higher success rate for SIBO prevention versus erythromycin but has been withdrawn from the US for safety reasons.113 Prucalopride (Resolor), 0.5 to 2 mg q.h.s., is not yet available in the US but is a safer alternative to tegaserod.114 It is presently available in Canada and Europe. A trial removal of a prokinetic at ≥3 months is suggested but continued long term use may be needed for some patients.115
A lower-carbohydrate diet is used in combination with a prokinetic to discourage a return of bacterial overgrowth. Once the breath test has normalized and small intestine damage has healed, the diet can be expanded beyond the strictness of the Specific Carbohydrate and SIBO Specific diets. The time frame for this is uncertain. Two studies have examined the rate of healing post SIBO and found that intestinal permeability normalized 4 weeks after successful SIBO eradication in 75% to 100% of patients.116,117 While these reports are very encouraging, they may or may not reflect the other repair needed post SIBO. Therefore, we currently suggest continuing a SIBO diet for 1 to 3 months post successful eradication. At this point, the Cedars-Sinai Diet, low-FODMAP Diet, or a similar diet may be adopted long term, as the patient tolerates.118,119 These diets allow more carbohydrates in the form of grains, gluten-free grains, cane sugar, and soy, though they still limit overall carbohydrate load.
Spacing meals 4 to 5 hours apart, with nothing ingested but water, allows for activity of the MMC.120 We have found this to be very helpful clinically. If a low-carbohydrate SIBO diet does not correct hypoglycemia, this strategy will need to be altered to allow for more frequent meals.
Hydrochloric acid or herbal bitter supplements, which encourage hydrochloric acid (HCl) secretion, may be used to decrease the load of incoming bacteria.121 When considering HCl supplementation, Heidelberg testing for HCl levels and response to treatments is the gold standard. Heidelberg testing reveals achlorhydria, frank hypochlorhydria, and hidden hypochlorhydria and allows individualization of dosing.
Probiotics are a controversial intervention in SIBO because lactobacilli have been cultured in SIBO and there is also concern about adding to the bacterial overload.122 Despite this, the few studies that have focused directly on probiotics for treatment of SIBO have shown good results. Bacillus clausii as a sole treatment normalized the breath test in 47% of cases.123 An 82% clinical improvement in SIBO was found using a combination of Lactobacillus casei and plantarum, Streptococcus faecalis, and Bifidobacterium brevis (Bioflora).124 Probiotic yogurt containing Lactobacillus johnsonii normalized cytokine responses, thereby reducing the low-grade chronic inflammation found in SIBO after 4 weeks.125 We have used various multistrain and single probiotics as well as yogurt and cultured vegetables with 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, MOS (mannose-oligosaccharide), and GOS (galactooligosaccharide). 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 are fermentable and could encourage bacterial regrowth. Specific nutrients we have used include lactose-free colostrum, 2 to 6 g q.d.; L-glutamine, 375 mg to 1500 mg q.d.; zinc carnosine, 75 mg b.i.d.; vitamins A and D, often given as cod liver oil, 1 tbsp q.d.; curcumin, 400 mg to 3 g q.d.; resveratrol, 250 mg to 2 g q.d. glutathione (oral liposomal), 50 to 425 mg q.d.; or glutathione precursor N-acetylcysteine 200 to 600 mg q.d., Supplements are given for 1 to 3 months, though may be continued long term for general benefit if desired. Higher dosages of curcumin and resveratrol are given for 2 weeks for the purpose of downregulating NF-kb, a mediator of increased intestinal permeability, and then reduced to maintenance levels.126–128 Herbal cholinergic support may include phosphatidyl choline, pantothenic acid, huperzine A (from Huperzia serrata), and N-aceytl-L-carnitine.129 Pranayama (yogic alternate nostril breathing) has been shown to have benefits in IBS-D by normalizing parasympathetic tone.130
If dampening of CNS inflammation is indicated, consider the use of green tea catechins, Curcuma longa, bioflavonoids, Scutellaria, resveratrol, Chrysanthemum morifolium leaf, and Matricaria chamomilla.131
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 4).
- Failure to use double antibiotic therapy for methane producers. Methanogenic flora need different antibiotic treatment than hydrogen-producing bacteria.
- Failure to utilize breath testing to identify if patients have SIBO, the type of gas that 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. Antibiotic treatment as a sole therapy typically leads to recurrence of hydrogen SIBO within 3 months and methane SIBO within 1 month.127
- Failure to use a low-carb preventative diet following treatment. Diet along with prokinetics is 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. One report found that the following conditions led to a poor response to antibiotics: anatomical abnormalities (adhesions, blind loops, diverticuli, superior mesenteric artery syndrome, etc.), chronic narcotic use, Addison's disease, scleroderma, colonic inertia, inflammatory bowel disease, and NSAID-induced intestinal ulceration.128 Some of these patients will need long term cyclical rotation of herbal treatments or, very rarely, a 550 mg single dose of rifaximin every other day in order to stay asymptomatic.
- Failure to find the underlying causes to allow for repair or modulation of the MMC will lead to a less desirable outcome.
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