The Missing Piece in SIBO Treatment: Beyond Eradication

Clinicians are becoming more aware of small intestinal bacterial overgrowth (SIBO) as a common culprit of their patients’ GI symptoms. Most clinicians are familiar with antimicrobial regimens for SIBO eradication; however, 44% of patients successfully treated for SIBO with antibiotics experience recurrence within 9 months.¹ Therefore, eradication alone may not resolve this problem.

SIBO is a condition that requires understanding the underlying mechanisms of dysfunction predisposing one to SIBO in the first place. When these factors are addressed, SIBO should not relapse, and remission periods are extended. This article will focus on natural therapies for successful SIBO management and long-term prevention.

Brief Introduction to SIBO

The gut microbiome is mainly housed in the large intestine, with a very small population of microbes inhabiting the small intestine. Small intestinal bacterial overgrowth (SIBO) is technically defined as a bacterial population exceeding 10³ colony forming units/mL. These organisms produce gases, including hydrogen, hydrogen sulfide, and methane, which are measurable on breath testing.^2,3

The overgrowth and gases are associated with many symptoms, including bloating, altered bowel habits, upper GI symptoms, and others. SIBO is not necessarily a true infection, but an overgrowth of normal flora, or sometimes other commensal species that do not normally inhabit the small intestine. Depending on the species present, various functions may be disrupted, resulting in distinct symptoms. For example, certain bacteria deconjugate bile acids, leading to fat malabsorption or bile acid diarrhea. Klebsiella species produce toxins that damage the mucosa, interfering with nutrient absorption and causing diarrhea.⁴ Intestinal methanogen overgrowth (IMO) slows transit, leading to constipation.⁵

Eradicating the overgrowth with antibiotics or antimicrobial herbs can certainly reduce the overgrowth and resolve symptoms. However, it’s imperative to work upstream on the root causes that allowed the overgrowth in the first place for long-term success. Otherwise, recurrence is likely and will require repeat testing and treatment.^6,7

There are numerous associated conditions and risk factors that can impair normal digestive function, predisposing to SIBO. The website siboinfo.com is a well-researched resource for clinicians wanting to learn more about these factors to help address root causes. Concurrently treating contributing diseases can help prevent SIBO.

Normal Physiology Keeps Overgrowth at Bay

The body is equipped to keep bacterial overgrowth under control. The primary physiologic mechanisms involve proper motility and digestive secretions to regulate bacterial populations in the small intestine. Ninety percent of SIBO cases are due to motility disorders and chronic pancreatitis.⁸

Immunoglobulins within intestinal secretions also help protect against bacterial overgrowth. Anatomical barriers are important. For example, the ileocecal valve prevents retrograde reflux into the small intestine from the large intestine. Optimizing healthy GI tract physiology is key to preventing SIBO.⁸

Gastrointestinal Motility

The migrating motor complex (MMC) is part of the enteric nervous system and sends “cleansing waves” throughout the small intestine to sweep bacteria and food debris down and out. The MMC functions in a fasted versus a fed state, and these waves are distinct from peristaltic waves that help move food while eating. When the MMC is damaged or impaired, motility is decreased, and the resulting stagnation creates an environment perfect for harboring bacteria and promoting overgrowth.^9,10

Motility dysfunction is associated with an almost 4-fold risk of SIBO compared to normal motility.²

One of the major etiologies of SIBO discovered by Dr. Mark Pimentel and his research group at Cedars-Sinai is that many cases of SIBO begin with gastroenteritis. The post-infectious irritable bowel syndrome (PI-IBS) that ensues may actually be a case of underlying SIBO.^3,11,12

A bug picked up during international travel or a bout of food poisoning produced a toxin that effectively crippled the MMC. The infectious organism is not implicated in SIBO, but the resulting disruption to physiology then sets the patient up for SIBO development, typically within a few months after their bout of gastroenteritis. A classic story is that the patient remembers their GI bug and their “gut has never been the same since.”

Diabetes, medications, anatomical abnormalities, hypothyroidism, autoimmune and other conditions interfering with intestinal neuromuscular function are also associated with MMC deficiency.^13-18

Digestive Secretions

Stomach acid, pancreatic enzymes, and bile acid all have bacteriostatic and bactericidal effects. Under normal physiologic conditions, secretion of these substances aids in healthy digestion and keeps microbial populations under control. On the contrary, conditions or medications that promote pancreatic insufficiency, hypochlorhydria, or gallbladder dysfunction can impair digestive capacity and lead to bacterial overgrowth.⁸

Not only can SIBO develop because of deficient digestive secretions, but the bacteria themselves can alter digestive output in a bidirectional relationship. For example, excess bacteria can deconjugate bile salts, resulting in malabsorption of fat and fat-soluble vitamins.⁸

A Functional Medicine Multiphasic Approach Addresses SIBO’s Root Causes

Since SIBO is a consequence of GI dysfunction, working upstream to address root causes and restore normal GI function should be the treatment focus. The goals and clinical benefits of a comprehensive protocol include microbial balance, optimized digestion, and motility. This comprehensive approach is the best way to achieve lasting remission, and studies show that a comprehensive approach using adjunctive therapies results in greater clinical improvement.^19,20

Phase 1: Eradicating Overgrowth and Modulating the Microbiome

Many are familiar with protocols for SIBO eradication, with the antibiotic rifaximin being the most studied. However, many clinicians and patients prefer a more natural approach, and there is evidence that botanical treatments are equivalent to rifaximin, if not superior. Botanical protocols tend to last 4 weeks but may require longer depending on the severity of the overgrowth or the formula used.^21,22

A study involving 104 patients with SIBO compared the effects of rifaximin (1200 mg per day) and an herbal formulation, both administered for 4 weeks. The herbal blends included Biotics FC-Cidal and Dysbiocide or Metagenics Candibactin AR and BR. The response rate was 46% for herbal therapies versus 34% for rifaximin. In patients with SIBO refractory to rifaximin, herbal therapies or triple antibiotics (clindamycin 300 mg TID, metronidazole 250 mg TID, neomycin 500 mg TID) were given for 4 additional weeks. SIBO clearance was similar in both rescue therapy groups, with 57.1% with negative breath testing after herbal therapy and 60% after triple antibiotic therapy. Fewer adverse effects were observed in the herbal treatment group compared to rifaximin.²²

Another clinical trial on 16 SIBO patients using 10 weeks of Biocidin liquid tincture and GI Detox+ showed negative breath tests in 42.8% of hydrogen-dominant SIBO and 66.7% of hydrogen sulfide-dominant SIBO patients. The botanical regimen also reduced facial erythema and beneficially modulated the microbiome and markers of intestinal permeability.²¹

Berberine is an extract from plants such as Berberis, Coptis, and Hydrastis, and has many known medicinal properties, including antimicrobial. Berberine is currently being studied in a clinical trial called the BRIEF-SIBO (berberine and rifaximin effects for small intestinal bacterial overgrowth) trial.²³ An interim report shows that two weeks of berberine has similar eradication rates as rifaximin with negative breath testing and clinical improvement.²⁴

Compared to antibiotics, herbs tend to have multiple mechanisms of action and, when combined with other herbs, can have a synergistic effect. Many herbs used in the clinical studies are well-documented for their antimicrobial properties, including oil of oregano, thyme, wormwood, yarrow, and horsetail, among others.^22,25-32 Herbs tend to have fewer side effects than antibiotics.²²

Herbs also possess anti-inflammatory and antioxidant properties, which can benefit gut lining integrity. Herbs such as French tarragon, horsetail, and olive leaf have antimicrobial and anti-biofilm effects.^33-36 With a similar response rate compared to antibiotics, a herbal SIBO treatment may be a more appealing option for restoring a healthy bacterial balance and improving gut health.

Another benefit of herbs over antibiotics is the ability to treat multiple microorganisms at once. For example, 34% of SIBO patients have coexisting small intestinal fungal overgrowth (SIFO), and most herbs used to treat SIBO also address fungal overgrowth.^37,38 SIFO symptoms overlap with SIBO, and there is no non-invasive test for SIFO; therefore, an herbal regimen that targets both SIBO and SIFO may be a better choice of treatment. Many antibiotic regimens predispose to yeast infections.

Phase 2: Restoring Healthy Digestive Physiology—The Natural Defense Against Bacterial Overgrowth

Perhaps the most important part of the SIBO journey is to address the underlying root causes to prevent relapse. This phase of treatment may last longer than the eradication phase, typically 3 months or longer. Some patients have underlying conditions that cannot be resolved and may therefore require ongoing preventive strategies to extend remission periods.

Strategies for Restoring Motility

Prokinetic agents stimulate and enhance gastrointestinal motility. It’s important to note that prokinetic agents are not laxatives. Prokinetics stimulate the MMC, whereas laxatives do not.^39,40 Prescriptive prokinetics have more research for SIBO as compared to herbal, however, many clinicians notice a benefit using herbal prokinetics.

• L-5-Hydroxy-Tryptophan (5-HTP) is the precursor to the neurotransmitter serotonin, which, in the GI tract, modulates intestinal smooth muscle contractile frequency.^41,42 5-HTP is also the precursor to 5-hydroxyindole (5-HI), a compound that accelerates GI motility.⁴³ 5-HTP is sourced from Griffonia simplicifolia
• Ginger’s (Zingiber officinale) bioactive compounds activate serotonin and muscarinic acetylcholine receptors, accelerating transit and regulating motility throughout the GI tract.⁴⁴ It stimulates gastric emptying and antral contractions and has been classically used to alleviate nausea.^45-47
• Artichoke extract (Cynara scolymus) stimulates bile acid secretion, and when used in combination with ginger, has been shown to promote gastric emptying and improve gastric motility.^48-50 Patients with functional dyspepsia (FD) experienced symptom relief in a randomized clinical trial using artichoke and ginger.⁵¹ There is a link between FD and SIBO, which both present with overlapping symptoms.⁵²
• Antioxidants and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione are important for preventing oxidative tissue damage. Oxidative stress causes damage to the enteric neurons, resulting in GI dysmotility.^53,54
• Nitric oxide (NO) acts as a neurotransmitter influencing motor activity in enteric nerve cells along the GI tract. Decreased production has been associated with motility dysfunction and delayed gastric emptying in humans.^55,56 Beet concentrate provides nitrates that promote NO production. Beets also provide antioxidants.⁵⁷
• Meal spacing every 4-5 hours and an overnight fast promote MMC activity. The MMC is not active during feedings.⁵⁸
• Stress management is crucial for nervous system balancing. The adage, “rest and digest,” refers to parasympathetic nervous system activity, as opposed to sympathetic dominance in a stressed, “fight or flight” state. Chronic stress decreases GI motility, gut mucosal immunity, and HCl production, and upsets microbial balance, contributing to SIBO.^10,59-62
• Address structural issues with manual therapy. Patients with prior abdominopelvic surgeries or trauma may have tissue adhesions, and manual therapy may promote better motility and digestive function.^63,64

Strategies for Supporting Digestion

Restoring physiologic levels of digestive compounds creates a more bacteria-resistant environment. It also encourages optimal digestion and absorption of nutrients that may have been affected by microbial imbalances.

• Betaine hydrochloride is a common supplement used for reacidifying the stomach. This provides antimicrobial defenses and promotes improved absorption of pH-dependent nutrients such as vitamin B12 and iron. Gastric juice also contains pepsin, a proteolytic enzyme with antimicrobial properties.^65-67 Proton pump inhibitors (PPIs) reduce hydrochloric acid, and a weaning program may be helpful if appropriate. PPI use is an independent risk factor for SIBO and SIFO.²
• Pancreatic enzymes assist in the digestion of lipids, proteins, and carbohydrates, as well as inhibiting bacterial overgrowth. Pancreatic enzyme replacement therapy (PERT) is not effective in all chronic pancreatitis patients, likely due to underlying SIBO. Therefore, it is important to eradicate the overgrowth (phase 1) for PERT to be effective in these patients.^68,69
• Bile salts assist in fat emulsification and have bacteriostatic and bactericidal activity against many microbial species, including methane-producing organisms.^70,71 A study on 24 patients with SIBO and FD showed a reduction in methane values on breath testing and FD symptoms after supplementing for 2 months with bile acid.⁷²

Address the Root Causes, Prevent SIBO Relapse

Treating the overgrowth is often the easy part, as most clinicians are well-versed in prescribing antimicrobial regimens for infections. Restoring optimal digestive function and treating co-occurring or predisposing conditions is necessary to prevent the vicious cycle of SIBO recurrence. Natural SIBO treatment protocols may require 4 months or longer. Providing support for the “2^nd phase” of SIBO treatment may be the missing piece to your long-term success rates with your SIBO patients.

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