Small Intestinal Bacterial Overgrowth (SIBO)

Small intestinal fungal overgrowth (SIFO) is characterized by a high quantity of fungi (such as yeast) in the small intestine, while SIBO is caused by elevated numbers of bacteria. Despite the conditions sounding similar, their risk factors, symptoms, and treatments differ.

Prescription antacids and altered gut motility may increase the risk of developing SIBO, but they aren’t associated with SIFO.^[26]

Studies have foundthat the rates of unexplained GI symptoms are similar in participants regardless of fungal colonization, which contrasts with the relationship between bacterial overgrowth and GI distress.

Also, while SIBO is conventionally treated with antibiotics, SIFO requires antifungal medications.^[29] Probiotics may prevent or suppress intestinal overgrowth of Candida (a type of yeast), but they don’t prevent SIBO.^[30][8]

However, in both cases, emerging research suggests that the composition of the fungi or bacteria — not simply a higher number of either — has a greater impact on whether the overgrowth might lead to symptoms.^[4][31]

It’s possible to have no symptoms at all, but SIBO often occurs with other GI diseases that have overlapping symptoms, which can complicate diagnosing either accurately.^[4] For example, antibiotics are more effective in cases of people who have both irritable bowel syndrome (IBS) and SIBO compared with IBS alone, which suggests that SIBO may play a direct role in some IBS symptoms.^[17] It could also explain the persistent GI symptoms in people with chronic pancreatitis who don’t respond to pancreatic enzyme replacement therapy.

Bloating, flatulence, nausea, abdominal pain, and diarrhea are some of the most common symptoms, but constipation may also occur in certain types of SIBO.^[1][3] Some theories suggest that SIBO may affect gut motility and induce constipation by altering the serotonin pathway that coordinates intestinal contractions or producing excess methane, which slows intestinal transit (the speed at which food moves through the intestines).^[3]

Anemia isn’t a primary symptom, but it has been identified as a predictor of SIBO. This may reflect a reduction in vitamin B12 absorption and could explain the fatigue people with SIBO sometimes have. SIBO is also associated with reduced nutritional status (the levels of nutrients in the body) in people with inflammatory bowel disease (IBD).

SIBO may contribute to malnutrition in IBD, Parkinson’s disease, and cirrhosis. It could also exacerbate liver disease by making the intestinal wall more permeable, which could allow bacterial contents to enter the bloodstream and cause inflammation.^[18][19] SIBO also has the potential to increase the risk of bacterial translocation — bacteria moving from inside the intestine to outside tissue — in susceptible individuals, such as people with chronic liver disease, who would then be at risk of life-threatening infection.^[20]

SIBO can be diagnosed with breath tests or a duodenal aspirate culture (a lab test done on a small fluid sample from the small intestine), but the lack of standardization makes accurate diagnosis challenging. Breath tests are an indirect way to measure bacteria in the small intestine, but their ease and low invasiveness make them a more common diagnostic tool than the fluid test.^[5][6]

During a breath test, the patient ingests a carbohydrate — usually glucose or lactulose — which is fermented by bacteria in the small intestine. The bacteria produce hydrogen and methane, which are expelled and measured in the patient’s exhaled breath. (Hydrogen sulfide is also produced, but only in recent years has it been added to some tests.) The quantity and production rate of these gasses can then be used to estimate the number of microbes in the small intestine, because gut microbes are the only source of hydrogen and methane. However, many factors, including the way the test is administered, can affect the results and lead to a false positive or false negative diagnosis, so these tests are likely to be less accurate than the duodenal culture method.^[5][6]

Sampling contents from the duodenum, a section of the small intestine, is a more direct way to measure the bacteria, but it’s highly invasive. This test requires intubating the patient, which involves inserting a tube into their throat and routing it through their stomach to reach the first section of their small intestine, where the clinician will aspirate (suction out) multiple samples of liquid. Swabs of the liquid are applied to cell culture plates that support the growth of many (but not all) types of bacteria in that sample, and the bacteria are eventually counted. Culturing methods could lead to false positives or false negatives due to sample contamination or improper growth conditions, respectively.^[5][6]

Clinicians have yet to reach a consensus on diagnostic criteria for a positive result of either test, but it’s generally accepted that SIBO is present when there is a concentration of 10^3–105 colony forming units per milliliter (CFU/mL) in a fluid sample. However, some researchers or clinicians consider that number to be greater than 10^5 CFU/mL.^[5][6]

Hydrogen and methane are produced exclusively by gut microbes, so an abnormal rate or quantity of gas production can indicate the presence of SIBO. The ratio of these gasses determines whether a person is predominantly a hydrogen or methane producer. When it comes to SIBO, these gasses could also provide clues to which microbes are thriving (overgrowing) in the small intestine.^[3]

While hydrogen is produced primarily by bacteria, most methane is produced by another group of microbes called Archaea, which belong to a domain of life separate from Bacteria or Eukarya (the cells that make up complex organisms, such as humans.) Archaea in the human gut consume hydrogen and carbon dioxide for energy, generating methane as a result, which is why they’re also known as methanogens.^[3]

An estimated third of healthy adults produce more methane than hydrogen, so methane hasn’t been identified as a clear cause of GI symptoms. Recent theories suggest that methane plays a role in constipation by slowing the GI system, however, and suggest differentiating between intestinal methanogen overgrowth and SIBO.^[3]

A recent meta-analysis reported that the odds of having methane-positive SIBO (possibly indicating methanogen overgrowth) were approximately two to three times higher in constipation-predominant IBS compared with diarrhea-predominant or mixed IBS, according to data from five studies.^[3]

Other research indicates that individuals with methane-positive breath tests are five times more likely to have constipation than people who primarily produce hydrogen.^[5] However, because slowing down of the GI system may support the growth of methanogens, it’s unclear which comes first: the methanogens or the constipation.^[3]

After fasting overnight, a breath test begins with the ingestion of a carbohydrate — most often glucose or lactulose when testing for SIBO — and the hydrogen and methane content of the person’s exhaled breath is measured at specific intervals over the next few hours. However, a number of factors can reduce the accuracy of breath tests and lead to a false positive or false negative.^[5]

The person being tested could reduce the accuracy of the test in the following ways:

• Using antibiotics within 4 weeks of testing
• Using laxatives or gut-motility drugs within a week of testing
• Not fasting long enough (8 to 12 hours) before the test
• Eating fermentable foods, such as complex carbohydrates, the day before the test
• Smoking before the test

The carbohydrate used during the test also affects the results. Glucose is more likely to lead to a false negative than lactulose, but glucose is regarded as a more accurate diagnostic tool. Lactulose is more likely to lead to a false positive by quickly reaching the large intestine, where hydrogen will be produced. Using too large a dose can speed up intestinal transit even more, leading to an early peak in gas production that could lead to a false positive.^[6][5]

Clinicians and researchers may also set their own cutoffs for the level of gas production required to diagnose SIBO, which would obviously have an impact on results.^[5]

SIBO is conventionally treated with certain classes of antibiotics that are poorly absorbed — unlike systemic antibiotics, which easily enter circulation — so they act primarily in the intestines. This leads to fewer side effects and lower chances of antimicrobial resistance, which leads to potentially deadly microbes becoming unaffected by antibiotics.^[7] SIBO is generally considered to be cured (often referred to as being eradicated or decontaminated) based on normal breath test results.^[8][5]

Antibiotics such as rifaximin, neomycin, and metronidazole have an eradication rate of 50 to 70%, making them an effective treatment option in many cases.^[7] One pilot study found that antibiotics reduced SIBO-related flatulence incontinence (uncontrollable gas) more effectively than an over-the-counter gas pill containing simethicone and activated charcoal.^[21]

Fecal microbiota transplants (FMT) aren’t an established treatment yet, but the results of a recent clinical study were promising. In the double-blind, placebo-controlled, randomized study, 55 patients with SIBO were assigned to take 16 oral FMTcapsules (from five healthy donors) or a placebo every week for 4 weeks. SIBO symptoms — abdominal pain, acid reflux, indigestion, diarrhea, and constipation — were lower after one month of FMT and remained lower than baseline until the final follow-up at 6 months; the placebo group experienced no change in symptoms.

Breath tests at 6 months were normal in the FMT group but not the placebo group. Fecal analysis also showed that the microbiota of the recipients changed after FMT, becoming more similar to the donors’ (who had greater microbial diversity than the recipients).

Larger studies are needed to confirm these findings, but the study design, confirmation of SIBO eradication via breath testing, and fecal analysis provide strong evidence that FMT changes the microbiota and may effectively treat SIBO.^[9]

Although SIBO hasn’t been identified as a definitive cause or consequence of any other disease, it is associated with a number of conditions that create an abnormal intestinal environment, which could include:

• A less acidic (more hospitable) small intestine
• Slower (more accessible) transit of food through the GI tract
• Abnormal muscular contractions that push contents (and microbes) backward, from the large to the small intestine
• Reduced immune activity that would normally regulate microbial growth

It is thought that these factors create a nutrient-rich environment that lacks the normal mechanisms for controlling microbial growth, and SIBO develops as a result.^[2][16]

Functional dyspepsia (commonly known as indigestion), IBS, IBD, diabetes (types 1 and 2), dysregulated gut motility (food moving more slowly through the intestines due to abnormal muscular contractions), chronic pancreatitis, chronic liver disease, Parkinson’s disease, and systemic sclerosis (an autoimmune disorder) are all associated with greater odds of a positive SIBO diagnosis. Limited evidence also suggests that females with IBS may be more likely to have SIBO compared with males who have IBS.^{[22][23][2][24][20][25][16][18][19][26]}

A history of GI surgery (such as gastric bypass or resectioning of the intestines), the use of acid-reducing proton-pump inhibitors (PPIs), and smoking are also associated with a greater likelihood of having SIBO.^[24][2][27]

Though celiac disease isn’t linked to an increased chance of having SIBO, one analysis observed higher rates of SIBO in people with celiac disease who were unresponsive to a gluten-free diet compared with healthy controls. However, most of the analyses detected inconsistencies and issues with the quality of studies used to determine the prevalence of SIBO in these conditions.^[28]