Rifaximin (Xifaxan): Why It May or May Not Improve Your SIBO

Rifaximin (Xifaxan) is one of the most common antibiotics prescribed for SIBO (small intestine bacterial overgrowth). It is a relatively safe antibiotic and can help reduce hydrogen-dominant bacterial overgrowth in the small intestine. There are, however, some drawbacks associated with its use, of which many people are sadly unaware. There are, however, ways to try to ensure that the antibiotic works properly to alleviate your SIBO and improve your digestive health!^{1 2}

Rifamycin Class of Antibiotics

The rifamycin class of antibiotics was discovered in the 1960s and is currently used to treat MAP, tuberculosis, SIBO, and MRSA (Methicillin-resistant Staphylococcus aureus). It was initially synthesized from Streptomyces mediterranei, now known as Amycolatopsis rifamycinica. The antibiotic inhibits bacterial DNA-dependent RNA synthesis. Antibiotics in the rifamycin class have an average side effect profile (gastrointestinal upset, diarrhea, headache). Still, they have also been associated with hepatotoxicity because they increase liver mitochondrial oxidative stress and decreased white blood cell counts. Antibiotics used in this medication class include rifampin, rifabutin, rifapentine, and rifaximin.³

Do not consume grapefruit fruit or juice while taking Rifaximin; it will significantly increase absorption, systemic circulation, and bodily concentration of the antibiotic.

Rifaximin is very special compared to other antibiotics in its class. What are the pros and cons of using rifaximin to treat SIBO over other antibiotics?

Rifaximin (Xifaxan) Pros

• Very poorly absorbed by the intestinal tract. Therefore, its antimicrobial effects only occur within the small intestine and not in other parts of the digestive system or systemically. Working only in the small intestine helps protect your microbiome outside the small intestine.^{4 5}
• Poor systemic bioavailability dramatically lowers the chance of liver toxicity associated with the rifamycin class of antibiotics, including rifaximin. Since it is not absorbed very well if at all by the intestinal tract it is not metabolized by the liver.⁶
• Rifaximin has a lower serious side effect profile. Like with most antibiotics, it can still cause gastrointestinal upset, headache, rash, and causing rare allergic reactions.⁷
• Lower chance of bacteria acquiring antibiotic resistance due to it only being effective in the small intestine and not affecting the microbiome of the entire body. It works well against most hydrogen-dominant bacteria, the main cause of SIBO-D.⁸
• It can prevent traveler’s diarrhea if it is caused by opportunistic E. coli.⁹
• May be effective against Clostridioides difficile dysbiosis of the jejunum and ileum of the small intestine if there is enough bile (C. diff may interfere with bile) to make it effective.^{10 11}

Rifaximin (Xifaxan) Cons

• Rifaximin requires bile to become both soluble and activated. Many people with SIBO have issues with bile production and fat digestion. If your stool is not dark brown when you defecate, or you have liver, gallbladder, or pancreatic problems causing you not to produce enough bile or digestive enzymes, the antibiotic may not work correctly. A possible alternative if you are having those issues is to take an ox bile supplement when you take rifaximin so that it can be appropriately utilized in the small intestine to help combat your overgrowth. The only drawback in taking an ox bile supplement with the antibiotic is that it may also activate it in the stomach and the duodenum and affect their microbiomes.¹²
• Rifaximin will do very little to help combat upper gut (upper part of the duodenum, stomach, esophagus, larynx, and oral cavity) dysbiosis. Bile is generally not found in this digestive tract area unless you are suffering from bile reflux. Therefore, rifaximin will not be activated and will work properly to reduce dysbiosis in these areas.¹³
• Rifaximin will also do very little to help combat sizable intestinal dysbiosis. Bile salts are reabsorbed mainly by your body and stool when reaching the ileocecal valve. Therefore, rifaximin will not work correctly in the large intestine to alleviate dysbiosis. The lack of bile salts in the large intestine might also explain why it is not systemically absorbed into the body.¹⁴
• Using an antibiotic like rifaximin or a natural antibacterial agent does not correct any of the direct causes of SIBO like a damaged MMC (motility), elevated stomach pH, diet, dysbiosis, leaky gut, malfunctioning ileocecal valve, or opportunistic biofilm formation, which might explain the possible high recurrence rate of SIBO after treatment.
• Rifaximin, even though it is better than other antibiotics used in treating SIBO in many aspects, it still reduces the probiotic microbiome of the small intestine. Supplementation of prebiotics to feed your probiotic microbiome during its use and after may help change the microbiome in someone with SIBO to a healthier microbiome. Ask your medical professional about trying the prebiotics 2-FL, GOS, arabinogalactan, or partially hydrolyzed guar gum to see if it improves your digestive health and helps to keep your SIBO in remission.¹⁵
• Rifaximin by itself is ineffective against methane-dominant Archaea that cause SIBO-C (constipation) or upper gut hydrogen sulfide dysbiosis. If you are dealing with SIBO-C, the rifaximin must be combined with other antibiotics like Flagyl, Cipro, Neomycin, or Alinia (the only one I recommend for SIBO-C) for it to be sufficient.

Rifaximin (Xifaxan) is an important treatment option in the fight against SIBO as long as its drawbacks are addressed in your wellness plan.

If you are taking rifaximin, please work with your healthcare professional to address these drawbacks to using the antibiotic by itself to help combat SIBO. If your healthcare professional is too busy and you need additional help contact me, and I will see how I can improve your digestive health!