Ozone Therapy for Small Intestinal Overgrowths (SIBO and SIFO) and IBS

At a Glance:

1. Small Intestinal Bacterial and Fungal Overgrowths are hard to diagnose and treat due to their location, biofilms, and the host’s pre-existing susceptibility to the overgrowth. 
2. These conditions are also poorly understood, as the gold standard test, endoscopic biopsy, is a very invasive procedure. The breath tests have varied reliability, such that some practitioners do not use them.
3. People with these overgrowths tend to have issues with gut movements, low stomach acid, bile flow, and weakened immune defense that may be linked to stress or other health issues. It’s crucial to work with a qualified practitioner to identify and address these underlying factors.
4. SIBO (and perhaps SIFO) are strongly linked to IBS, but they’re not one and the same. You can have these overgrowths with no gut issues or no issues at all. Still, the overgrowths can also contribute to conditions like fibromyalgia, chronic fatigue syndrome, anxiety/depression, and endometriosis.
5. SIBO and SIFO typically do not resolve with one single therapy—they require a whole-person approach. Ozone therapy, including oral ozone oil or water, may be beneficial by supporting the host's terrain, regenerating the mucosal barrier, improving detoxification, and breaking down biofilms. 

Small intestinal overgrowths are some of the tougher conditions to diagnose and address, partly due to biofilms and the weakened terrains. This article explains what we know so far about these conditions, along with how ozone therapy may help. Small intestinal overgrowths tend to be complex cases that may not resolve with any single therapy, although ozone therapy may be very helpful. 

Due to their location in the small intestine, these overgrowths and infections may be very difficult to noninvasively diagnose. Symptoms tend to be very similar among these types of infections, and they can co-occur, yet the most effective targeted treatments are different. Also, these infections can only happen when the host terrains are compromised, be it low stomach acid, poor gut motility, or suboptimal gut immune defenses. Given that ozone therapy improves immune defense, regenerates the gut mucosal barrier, kills microbes, and breaks biofilms, it might be especially helpful for these infections.

What Is Small Intestine Bacterial Overgrowth (SIBO)?

Small Intestinal Bacterial Overgrowth (SIBO) refers to an abnormal increase in the number or type of bacteria in the small intestine [1]. 

Normally, the small intestine harbors relatively few bacteria compared to the colon. In SIBO, excessive fermentation occurs in the upper GI tract. This contributes to gas production, inflammation, and nutrient malabsorption. Researchers believe that SIBO may cause irritable bowel syndrome (IBS) and contribute to several other chronic conditions.

Common symptoms of SIBO include [2]:

• Bloating and distension (often within 1–2 hours after eating)
• Abdominal pain or cramping
• Excessive gas or belching
• Diarrhea, constipation, or alternating patterns
• Fatigue or brain fog (due to malabsorption or systemic inflammation)
• Nutrient deficiencies (especially B12, iron, and fat-soluble vitamins)

Even though SIBO is frequently discussed in integrative and functional medicine circles, it remains controversial in conventional gastroenterology [3]. It’s less clear-cut than other conditions, as current SIBO diagnostic tests may not be reliable or indicative of SIBO severity. Also, it’s unclear whether treating the bacterial overgrowth is necessarily beneficial, as the overgrowth could be secondary to other issues.

The gold standard for diagnosis is jejunal (small intestine) aspirate culture, but this is invasive and rarely performed, except for research [4]. More commonly, SIBO is diagnosed using breath tests, typically using lactulose or glucose as substrates that the bacteria can ferment. These tests measure exhaled hydrogen and methane gases, and less commonly, hydrogen sulfide [5].

As a gut infection, SIBO is linked to IBS [6]. However, not all IBS cases are caused by SIBO, and not all cases of SIBO meet the diagnostic criteria for IBS. In fact, it’s totally possible to have SIBO with no digestive symptoms or no other symptoms. 

Each gas profile can offer clues:

• Hydrogen-dominant SIBO often correlates with diarrhea [7].
• Methane-dominant SIBO (now reclassified as IMO) tends to cause constipation [8].
• Hydrogen sulfide SIBO may cause loose stools and has a distinct "rotten egg" smell on the breath [9].

However, breath testing has limitations in sensitivity, specificity, and interpretation. False positives and negatives are common, especially in patients with rapid or delayed transit times [10]. 

Despite these challenges, many practitioners acknowledge that a subset of IBS patients likely have small intestinal dysbiosis, and when treated accordingly, experience significant symptom improvement. 

Current treatments for SIBO

Antibiotics (herbal or pharmaceutical)

One of the most common and widely accepted treatments for SIBO is antibiotic therapy, particularly with rifaximin, which stays in the gut [11]. 

In methane-dominant or mixed cases, rifaximin is often paired with other antibiotics like neomycin or metronidazole to broaden antimicrobial coverage. 

These medications work by reducing bacterial load in the small intestine, but their success is often temporary: 

• High relapse rates: Up to 45–60% of patients relapse within 3–9 months after treatment, often requiring repeated or prolonged courses.
• Biofilm resistance: Antibiotics often fail to penetrate microbial biofilms, which protect bacterial colonies and allow them to repopulate quickly once therapy ends [12].
• Microbiome disruption, leading to fungal overgrowth, C. difficile risk, or other unintended shifts in the gut ecosystem.

Prokinetics

Prokinetics are medications or supplements used to stimulate gut motility and restore the activity of the migrating motor complex, the rhythmic cleansing gut movements that happen between meals. 

Since impaired motility is one of the core drivers of SIBO recurrence, prokinetics are often recommended after antimicrobial treatment to maintain remission and reduce the likelihood of relapse [13].

Commonly used prokinetic agents include:

• Low-dose erythromycin (a motilin receptor agonist)
• Prucalopride (a serotonin 5-HT4 receptor agonist)
• Ginger extract or botanical blends with carminative and pro-motility properties [14]

Despite their usefulness, prokinetics come with limitations:

• Limited access or approval: Some prescription options are not available in all countries or are off-label for SIBO.
• Tolerance: Certain agents may become less effective if used chronically.
• Side effects: Ranging from mild (nausea, cramping) to more serious, depending on the compound.
• Incomplete efficacy: Not all patients respond well.

Prokinetics are best viewed as supportive therapy, rather than a stand-alone treatment. 

They do not reduce bacterial load or repair gut lining function, and they don’t address the underlying causes of impaired motility, such as inflammation, trauma, or immune-mediated damage to enteric neurons.

Low FODMAP diet

The Low FODMAP diet is short for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. 

Low FODMAP is a dietary strategy designed to reduce symptoms of bloating, gas, and abdominal discomfort by restricting certain types of rapidly fermentable carbohydrates [15]. 

These carbohydrates are poorly absorbed in the small intestine and readily fermented by gut bacteria, producing hydrogen, methane, or hydrogen sulfide gas [16].

In the context of SIBO or IBS, a low FODMAP diet can:

• Reduce symptom severity, particularly bloating and pain after a meal.
• Temporarily decrease available fuel for overgrown bacteria.
• Improve quality of life scores in some patients with IBS or SIBO-like presentations.

However, this diet is not without drawbacks [17]:

• Does not address the root cause of bacterial overgrowth, only the symptoms.
• Can reduce microbial diversity in the large intestine if followed long term, potentially weakening beneficial species and contributing to further dysbiosis.
• May lead to nutrient gaps, particularly in fiber, prebiotics, and polyphenols.
• Requires strict adherence and multiple phases, which can be difficult for patients to sustain. 

The Low FODMAP diet is best used as a short-term intervention, ideally under the guidance of a qualified practitioner. Some clinicians believe restrictive diets are best, while others believe in keeping the most diverse diet that the patients can tolerate.

Its role is to reduce the symptom burden while the underlying causes of SIBO, such as motility dysfunction, immune imbalance, or prior infection, are addressed through other means.

Probiotics

Probiotics are often used for SIBO, but their role remains controversial and highly individual. 

While they have potential to support microbial balance, not all probiotic strains are equally beneficial, and in some cases, they may worsen symptoms.

Many standard formulations contain lactic acid bacteria (LAB) species such as Lactobacillus and Bifidobacterium, which can be problematic in SIBO due to [18]:

• Their ability to ferment carbohydrates and produce gas
• Their tendency to colonize the small intestine when motility is impaired
• Reports of increased bloating, brain fog, and discomfort in sensitive individuals [19]

Some patients with SIBO-like symptoms who take LAB probiotics often report significant improvement after discontinuation, suggesting that certain strains may exacerbate SIBO in some cases [20].

However, spore-based probiotics, such as Bacillus subtilis or Bacillus coagulans offer a more favorable profile for SIBO [21], [22]:

• They transit through the small intestine without colonizing it, reducing risk of overgrowth.
• They survive gastric acid and bile, reaching the colon intact.
• They can modulate local immunity, reduce inflammation, and help normalize intestinal transit.

That said, not all SIBO patients tolerate probiotics well, even spore-based ones. Their use should be individualized, introduced cautiously, and assessed for response.

What Is Small Intestinal Fungal Overgrowth (SIFO)?

Small Intestinal Fungal Overgrowth (SIFO) is a condition characterized by an excessive presence of fungal organisms, most often Candida species, within the small intestine [23]. 

SIFO can present very similarly to SIBO, and some patients have both SIBO and SIFO.

In a perfectly optimal gut, the small intestine is not hospitable to fungi due to chemical barriers like stomach acid, bile, and digestive enzymes, along with cleansing gut movements.

When these defense mechanisms are impaired, fungal organisms can grow, contributing to a range of nonspecific but often disruptive gastrointestinal symptoms.

Clinical Presentation and Diagnostic Challenges

Patients with SIFO often report symptoms indistinguishable from those seen in SIBO or functional gastrointestinal disorders such as IBS [23]. The contributing factors to SIFO tend to also be very similar to SIBO.

SIFO symptoms may include:

• Bloating
• Excessive gas
• Abdominal discomfort
• Loose stools
• Altered bowel patterns

In some cases, these symptoms persist despite antibiotics. Often, antibiotics can allow for more fungal overgrowth. 

The clinical standard for diagnosis is a small bowel aspirate obtained during endoscopy and cultured for fungal species [12]. The most common culprit is Candida albicans. Due to the invasive nature, the bowel aspirates tend to be reserved for research purposes. Instead, clinicians rely on other clues, such as:

• The detection of fungi or Candida by stool tests, urine organic acids test, or other markers of fungal infections 
• Fungal infections elsewhere in the body, such as toenail, vagina, skin, thrush, and urinary tracts
• Improvements of symptoms in response to antifungal treatments or anti-Candida diets.

Breath tests typically do not diagnose SIFO and may miss cases entirely.

Standard treatments for SIFO

Treatment for SIFO typically involves:

1. Antifungal agents like fluconazole or nystatin, administered over a short course [12]. Some practitioners use natural antimicrobials such as oil of oregano or monolaurin.
2. An anti-Candida diet, which cuts down sugar, refined carbohydrates, and inflammatory foods. However, there is no consensus on the best Candida diet in the literature or among clinicians. 
3. Probiotics, which may be LAB or spore-based probiotics. 

In the largest study to date, patients with confirmed SIFO who received antifungal therapy reported significant clinical improvement [24].

That said, the long-term benefit of treatment remains uncertain. Fungal organisms, particularly Candida, are resilient and often form biofilms that make eradication more difficult. 

Since any fungal infection is an opportunistic infection, recurrence can be very common, especially if underlying causes are not addressed.

Causes and pathology of SIBO and SIFO

SIBO and SIFO have such similar causes that they can co-occur in the same patients. In a study of 150 subjects (47 males and 103 females) with unexplained digestive complaints [24]:

• 94/150 (63%) had some type of detectable small intestinal overgrowths
• 38/94 (40%) had SIBO
• 24/96 (26%) had SIFO
• 32/94 (34%) had mixed SIBO and SIFO
• 80/150 (53%) had gut dysmotility
• 65/150 (43%) had a history of PPI use

This speaks to the importance of addressing the root causes that allow SIBO and SIFO to occur as much as to using antimicrobials to treat the overgrowth. 

Poor gut movement/damaged MMC

Dysfunction of the migrating motor complex (MMC)—a sweeping, wave-like muscular contraction that occurs in the fasting state—can be a driver of SIBO and SIFO [25], [24]. 

The MMC acts as a “cleansing” mechanism, pushing residual food, bacteria, and cellular debris forward into the colon. It’s often referred to as the intestinal housekeeping system.

In healthy individuals, the MMC activates roughly every 90–120 minutes between meals and plays a critical role in preventing bacterial stasis and retrograde colonization of the small intestine.

Impaired or absent MMC can make the small intestine vulnerable to overgrowth, as is commonly seen in patients with [26]:

• IBS
• Post-infectious gastroenteritis
• Disrupted autonomic signaling

Instead of being periodically flushed forward, microbes from the colon or oral cavity can migrate upward or remain stagnant in the upper small intestine, where they ferment carbohydrates and release gas.

Several factors can damage the MMC [27], [28], [29]:

• Vagal nerve dysfunction (common in chronic stress and trauma)
• Autoimmunity targeting enteric (gut) nerves
• Use of opioids or other medications that slow GI motility
• Diabetes
• Hypothyroidism

Over time, this motility dysfunction creates a microenvironment of stagnation and fermentation. The microbial biofilms on the mucosal barrier can also contribute to low-grade inflammation, while protecting the microbes from the immune response or digestive secretions meant to eradicate them. 

Low stomach acid

Contrary to popular belief, many individuals with reflux, bloating, or upper abdominal discomfort don’t suffer from excess stomach acid, but insufficient hydrochloric acid (HCl) production: hypochlorhydria, which can arise from: 

• Chronic stress
• Long-term proton pump inhibitor (PPI) or antacid use
• Aging, as gastric acid production declines over time
• H. pylori infection

This is a significant and often overlooked contributor to SIBO.

Stomach acid serves as a first line of defense in the digestive tract, sterilizing incoming food and preventing pathogens or bacteria from reaching the small intestine. 

When acid levels are low, oral and dietary microbes survive, increasing the likelihood of bacterial colonization further down the GI tract [30].

Low stomach acid contributes to SIBO and SIFO in several ways [31]:

• Decreased microbial kill rate
• Impaired protein digestion
• Poor bile and pancreatic enzyme release
• Impaired gut movement, as the gut content’s acidity triggers some movements in the gut

When stomach acid is low, the entire digestive cascade becomes dysregulated [31]. This contributes not only to SIBO and SIFO, but also to nutrient malabsorption, particularly of:

• Vitamin B12
• Zinc
• Iron
• Calcium

These nutrients are essential for gut lining repair, enzyme function, and immune regulation.

Anatomic issues

In some cases, structural abnormalities in the gastrointestinal tract create physical environments that promote bacterial overgrowth. 

These anatomic issues interfere with the normal flow of contents through the small intestine, creating the stagnation that allows the microbes to settle down and ferment the gut content [32].

Common anatomic contributors include:

• Adhesions: Scar tissue from previous abdominal surgeries can create kinks or narrowed segments in the small intestine, slowing transit.
• Strictures or narrowing: Inflammatory conditions such as Crohn’s disease can lead to strictures that obstruct flow.
• Diverticula (particularly in the jejunum): Pouch-like herniations in the small intestine can become pockets of trapped bacteria.
• Ileocecal valve dysfunction or removal: This valve prevents backwards movement of colonic bacteria into the small intestine. When it’s surgically removed or not functioning, bacteria can migrate backward [33].
• Post-radiation: Pelvic or abdominal radiation and some cancer surgeries can alter intestinal structure and slow motility [34].
• High BMI

Weakened immune function

The small intestine is not just a digestive organ, it’s a highly active immune interface, home to an estimated 70–80% of the body’s immune cells. 

The mucosal immune system continuously monitors the environment, distinguishing between food antigens, commensal microbes, and potential pathogens.

When this immune surveillance system is compromised, it creates an opportunity for bacterial overgrowth and dysbiosis, laying the groundwork for small intestinal infections.

Several forms of immune dysfunction can contribute to small intestinal infections:

• Secretory IgA (sIgA) deficiency: The sIgA antibody is the first line of immune defense in the gut lining. Low sIgA levels reduce the ability to neutralize and clear microbes [35].
• Impaired mucosal barrier function: Chronic stress, infections, or medications can damage the epithelial barrier and tight junctions, allowing bacterial translocation. This "leaky gut" state fuels a cycle of inflammation and immune exhaustion [36].
• Autoimmunity: In post-infectious IBS, autoantibodies against enteric (gut) neurons (e.g., anti-vinculin, anti-CdtB) can impair gut motility and immune coordination [37].
• Chronic infections: Reactivated viruses, parasitic infections, or persistent bacterial triggers may tax the immune system [38].
• Immunosuppressive drugs: Corticosteroids or biologics used for other inflammatory conditions can blunt the local immune response, indirectly encouraging small intestinal overgrowths [39].

Unhealthy diets

Diet plays a pivotal role in shaping the microbial landscape of the small intestine. 

While small intestinal overgrowths are not caused by food alone, unhealthy or poorly timed dietary patterns can fuel bacterial overgrowth, disrupt motility, and exacerbate symptoms [40].

Several dietary habits commonly linked to these overgrowths include:

• Frequent snacking inhibits the migrating motor complex.
• High sugar/refined carbohydrate intake feeds gas-producing and fungi.
• Low-fiber or processed diets reduce support for beneficial bacteria and may allow opportunistic species to dominate.
• Excess alcohol consumption increases gut permeability, suppresses immune function, and favors bacterial overgrowth.
• Poorly managed food sensitivities can inflame the gut lining and weaken the immune barrier, encouraging bacterial migration or stasis.

Ongoing or past infections, such as food poisoning

Many cases of SIBO can be traced back to a single infectious event, most commonly bacterial gastroenteritis from contaminated food or water. 

For others, SIBO develops slowly following chronic low-grade infections in the gut or malfunctions in the adjacent systems. 

The most well-documented mechanism involves post-infectious IBS (PI-IBS), where a case of food poisoning (from pathogens like Campylobacter, E. coli, or Salmonella) leads to the production of cytotoxin-associated antibodies [41]. 

These antibodies can cross-react with vinculin, a protein involved in enteric nerve function, and damage the interstitial cells of Cajal, the pacemakers of the migrating motor complex. The result: impaired motility, stasis, and a high risk of SIBO [42].

Additionally, persistent infections such as H. pylori, parasites, and viruses can make the small intestine more hospitable to opportunistic overgrowths [43], [44], [45].

Medications

Key medication classes associated with small intestinal overgrowths include:

• Proton pump inhibitors (PPIs) [46]
• Opioids
• Antibiotics
• Antidepressants (tricyclics, SSRIs)
• Oral contraceptives
• Immunosuppressants (e.g., corticosteroids, biologics)
• GLP-1 agonists

Long-term use of these medications, especially in combination, can increase susceptibility for small intestinal infections. 

Toxic exposures 

Various toxic substances, such as mycotoxins, can impair gut movement and immune responses, which lead to small intestinal overgrowths and conditions like gastroparesis. 

Ozone Therapy for Small Intestinal Overgrowths – Published Evidence

Ozone therapy serves as a tool to improve the terrain and improve the gut flora, and may help break biofilms. Since these conditions are complex, most cases do not resolve with any single therapy, but rather require a comprehensive approach. 

Ozone therapy, including oral ozone oil and drinking ozone water, may help with SIBO, SIFO, and IBS by:

• Re-normalizing inflammation and oxidative stress, which may reduce autoimmunity
• Jumpstarting local immune responses
• Breaking biofilms and delivering nonspecific antimicrobial activities where the microbes cannot develop resistance
• Stimulating regenerative processes in the gut lining
• Oxidizing the anaerobic microbes that thrive in low oxygen environments
• Improving the intestinal flora (for rectal insufflation)

Ozone rectal insufflation and drinking water

Study 1: A randomized clinical trial of 48 adults diagnosed with IBS investigated the effects of ozone therapy on gut microbial balance and motility [47].

Patients were randomized into two groups: a control group (20 patients) who received 10 sessions of interferential therapy (a form of electrotherapy), and an ozone group (28 patients) who received interferential therapy plus:

• Oral ozonated distilled water (150 mL at 5 mg/L ozone) three times daily, 30 minutes before meals for 3 weeks.
• 8 rectal insufflations of ozone-oxygen gas (200 mL at 15 mg/L).

Ozone treatments resulted in:

• Significant improvement in gut microbiota.
• Normalized bowel motility and faster transit times, demonstrated via radiological assessment.
• Significant improvements in IBS symptom scores.

Study 2: A clinical study of 34 adults diagnosed with intestinal dysbiosis investigated whether a combination of ozonated water and rectal ozone therapy could alleviate the wide-ranging symptoms of dysbiosis [48].

Over a 90-day period, subjects received:

• Hyper-ozonated water, taken orally.
• Rectal insufflation of an oxygen-ozone (O2-O3) gas mixture.

Researchers used a visual-analogue scale (VAS) to track symptom severity at baseline.

Treatments results showed:

• All symptoms showed significant improvement by day 45, which became even more pronounced by day 90.
• Decreases in urinary indican and skatole suggesting a rebalancing of gut flora and restoration of digestive function.

This study supports the dual administration strategy used: oral ozonated water paired with rectal insufflation, may offer a compelling non-antibiotic, microbiome-restorative approach for patients unresponsive to other therapies.

This study serves not only as a validation of ozone therapy’s therapeutic promise, but also as a call to reconsider gut dysbiosis as a root cause of many modern chronic conditions, and to treat it accordingly with tools that go beyond symptom suppression.

Study 3: A rat study investigated how ozone influences intestinal mucosal homeostasis [49].

Adult rats (250–280 g) were divided into three experimental groups (8 per group):

• Control Group: Received 2 mL of water orally and intraperitoneally (IP) for 5 days.
• O3-PO Group: Received 2 mL of an ozone/oxygen mixture orally and 2 mL of water IP for 5 days.
• O3-IP Group: Received 2 mL of water orally and 2 mL of an ozone/oxygen mixture IP for 5 days.

On day 6, all animals were sacrificed and assessed for:

• Bowel and mucosal weight
• Mucosal DNA and protein content
• Villus height and crypt depth
• Enterocyte (intestinal cell) proliferation and apoptosis rates

Results of the experiment showed that the O3-IP group had:

• Significantly greater villus height and crypt depth in both the jejunum and ileum.
• Increased enterocyte proliferation in the jejunum.
• Reduced enterocyte apoptosis in the ileum.
• The O3-PO group (ozone delivered orally) showed modest improvements, but not as pronounced as the IP group.

By stimulating cell regeneration and reducing cell death, ozone appears to promote intestinal resilience and functional recovery, something that is important for IBS and SIBO.

The intraperitoneal route was more effective than oral delivery in this model, suggesting that specific deliveries to the gut may improve treatment outcomes.

Still, even partial oral benefits reinforce the concept that ozone therapy may provide mucosal protection.

Ozone oil capsules

Currently, there is no published clinical trial showing that ozone oil capsules may help with SIBO or SIFO. However, given that they have nonspecific antimicrobial and biofilm-breaking activities, oral ozonides may be beneficial as part of the protocols to address small intestinal overgrowths. Anecdotally, many people find these ozone oil capsules to be effective against intestinal parasites.

The links between IBS, SIBO/SIFO, and other conditions

Irritable Bowel Syndrome (IBS) is a diagnosis of exclusion where all other causes are ruled out [50]. Typically, symptoms may include diarrhea, constipation, or a mix of both. 

The most widely used diagnostic criteria are the Rome IV Criteria, which define IBS as [51]:

“Recurrent abdominal pain, on average at least 1 day per week in the last 3 months, associated with two or more of the following criteria”:

• Related to defecation
• Associated with a change in stool frequency
• Associated with a change in stool form (appearance)

These symptoms must be present for at least six months prior to diagnosis, with no other explanatory pathology found through labs, imaging, or endoscopy.

In clinical practice, IBS is frequently accompanied by bloating, urgency, stool mucus, and incomplete evacuation [52]. It’s also common to experience fatigue, anxiety, and brain fog. In other words, IBS is more than a local gut disorder, it reflects dysfunction in the brain-gut-microbiome axis [53].

Importantly, while IBS is considered "non-inflammatory" by conventional standards, recent studies have detected low-grade inflammation, mucosal barrier dysfunctions, and gut flora disruption [54].

This evolving understanding opens the door for bioregulatory interventions like ozone therapy, which target systemic dysfunction rather than just the symptoms alone.

Conditions that tend to be comorbid with IBS

Systemic ozone therapy helps with some of the comorbid conditions, such as chronic fatigue and fibromyalgia. While ozone therapy is not a panacea, it may help with certain physiologic aspects that contribute to IBS. 

Gastroesophageal Reflux Disease (GERD)

Many individuals (up to 35%) with IBS also experience reflux [55]. Shared factors include:

• Altered gut motility
• Visceral hypersensitivity
• Vagal nerve dysfunction

Fibromyalgia

Both IBS and fibromyalgia involve central sensitization and dysregulation of the nervous system. Up to 60% of fibromyalgia patients report IBS-like symptoms [56].

Chronic Fatigue Syndrome / ME (CFS/ME)

Overlaps include [57]:

• Gut-brain axis dysfunction
• Mitochondrial impairment
• Altered microbiota 

Fatigue often correlates with GI flare-ups, and may be comorbid in around 40% of patients.

Interstitial Cystitis / Bladder Pain Syndrome (IC/BPS)

Pelvic pain and urinary frequency co-occur with IBS in approximately 20% of patients. Cross-talk between pelvic organs and shared inflammatory or pain perception pathways are likely contributors [58].

Endometriosis

IBS symptoms are often misattributed to or exacerbated by endometriosis. Inflammation and hormonal imbalances may link both conditions, to the extent of a threefold increased risk of developing IBS [59]. 

Anxiety and Depression

IBS patients show higher rates of mood disorders, with up to one third of patients having anxiety or depression. This is likely due to [60]:

• Dysregulation of the gut-brain axis
• Altered neurotransmitter levels
• Chronic symptom burden

Histamine Intolerance / Mast Cell Activation

Up to 60% of IBS patients are reactive to high-histamine foods [61]. 

Increased mast cell density in the gut and histamine-driven motility changes may be involved.

Celiac Disease and Non-Celiac Gluten Sensitivity (NCGS)

Though mechanistically distinct, these conditions can present with IBS-like symptoms in up to one third of patients [62]. Gluten-related gut barrier disruption and immune activation may mimic or worsen IBS.

Conditions that often are comorbid with SIBO

Other than the conditions that are comorbid with IBS above (which are also comorbid with SIBO), the following conditions seem to have a clear link. 

Hypothyroidism

Slowed intestinal transit from reduced thyroid hormone levels can reduce gut movement, creating ideal conditions for SIBO and SIFO in over 50% of patients [63]. 

Ehlers-Danlos Syndrome (EDS)

This connective tissue disorder can affect gut motility and structure, increasing the risk for stasis and SIBO amongst 35% of patients [64]. 

Rosacea

Patients with rosacea have higher rates of SIBO, possibly due to shared immune or microbial dysregulation [65].

Crohn’s Disease (especially post-surgical)

Structural changes from inflammation or resection (e.g., ileocecal valve removal) may lead to bacterial backflow and overgrowth in over half the cases [66].

Gastroparesis

Delayed gastric emptying allows prolonged fermentation in the upper GI tract, increasing the risk for SIBO in up to 40% of cases [67].

Liver Cirrhosis / Portal Hypertension

Impaired detoxification and altered bile flow can change the microbial environment, predisposing to overgrowth [68].

Conclusion

Small intestinal overgrowths (SIBO and SIFO) and IBS are obscure, poorly understood, and hard to diagnose and treat. These overgrowths can contribute to or be a result of other chronic illnesses. To successfully treat them, it’s crucial to work with a practitioner to holistically address contributing factors and your gut terrain before introducing the antimicrobials. Ozone therapy may be a tool in the toolbox to support you systemically, or which can be taken orally to break biofilms and kill the overgrown microbes.

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