Comparison Table Of IBS Tests
Confirming an IBS diagnosis can be tricky. Some of the complexity is because there are no tests that can give a straightforward definitive yes or no to whether or not someone has IBS. Additionally, there are other disorders that share symptoms with IBS, so if patients do not respond to their initial treatments for their primary symptoms (diarrhea, constipation, pain/discomfort), testing for other causes of their symptoms may be warranted.1 These include but are not limited to inflammatory bowel disease (IBD), Celiac disease, bile acid malabsorption, SIBO, pelvic floor disorders, etc. A concern with IBS management is testing that can often be unnecessary or performed too broadly or frequently. Unnecessary testing can result in avoidable medical costs and further delay diagnosis and treatment.2 Researchers and physicians from the American College of Gastroenterology (ACG) have worked to make unified evidence-based recommendations on when and what tests to use in IBS. Not all tests have clear guidelines on when to use them, and ultimately which tests are needed will be up to your doctor. Keep in mind that not all tests we discuss are perfect or definitive, with some tests having increased chances of either false-positives or false-negative results. Below we will go over tests that are associated with IBS. As you will see, not all of them are necessary for all patients with IBS.
Blood Tests
Test Type
Description
ACG Recommendations
When it’s typically used in IBS
1
Complete Blood Count (CBC)
An order set that contains a number of different labs like red blood cell count, hemoglobin, hematocrit, platelet count, etc.
n/a
- Yearly checkups
- IBS patients with alarm symptoms
2
Complete Metabolic Panel (CMP)
An order set that contains a number of different labs like glucose, calcium, albumin, sodium, creatinine, etc.
n/a
- Yearly checkups
- IBS patients with alarm symptoms
3
C-reactive protein (CRP)
Inflammatory marker used to test for IBD
‘We suggest that either fecal calprotectin or fecal lactoferrin and C-reactive protein be checked in patients without alarm features and with suspected IBS and diarrhea symptoms to rule out IBD.’
- Generally used in patients with diarrhea needing to rule out IBD
4
Erythrocyte Sedimentation Rate (ESR)
Inflammatory maker used to test for IBD
N/a
- Generally used in patients with diarrhea needing to rule out IBD
5
IgA anti-tissue transglutaminase and Quantitative serum IgA
Antibody testing for Celiac Disease (CD)
‘We recommend that serologic testing be performed to rule out CD in patients with IBS and diarrhea symptoms.’
- Generally used in patients who eat gluten and have diarrhea symptoms and are suspected of having CD
6
Anti-endomysial antibodies (EMA)
Antibody testing for Celiac Disease (CD)
‘We recommend that serologic testing be performed to rule out CD in patients with IBS and diarrhea symptoms.’
- Generally used in patients who eat gluten and have diarrhea symptoms and are suspected of having CD
7
HLA-DQ2/DQ8 haplotype testing
Genetic testing for Celiac Disease (CD)
N/a
Generally used in those suspected of CD who are following a GF diet and have a difficult time being diagnosed
Stool Tests
Test Type
Testing For
ACG Recommendations
When it’s typically used in IBS
8
Fecal Calprotectin and Fecal Lactoferrin
Inflammatory markers found in stool
‘We suggest that either fecal calprotectin or fecal lactoferrin and C-reactive protein be checked in patients without alarm features and with suspected IBS and diarrhea symptoms to rule out inflammatory bowel disease.’
- We recommend against routine stool testing for enteric pathogens in all patients with IBS.’
9
Enteric pathogens
The presence of a virus, bacteria, or parasites in stool
‘We recommend against routine stool testing for enteric pathogens in all patients with IBS.’
- When there is a high risk for Giardiasis, a parasitic infection
Breath Tests
Test Type
Testing For
ACG Recommendations
When it’s typically used in IBS
10
Hydrogen Lactulose and Glucose
The presence of hydrogen in specific amounts in the breath.
‘We suggest the use of breath testing (glucose or lactulose hydrogen) for the diagnosis of SIBO in patients with IBS.’
- When IBS patients are suspected of having SIBO
11
Methane
The presence of methane in specific amounts in the breath.
‘We suggest testing for methane using glucose or lactulose breath tests to diagnose the overgrowth of methane-producing organisms (IMO) in symptomatic patients with constipation.’
- When IMO is suspected in patients with constipation.
12
Lactose
The presence of hydrogen in specific amounts in the breath.
n/a
- When patients with diarrhea are suspected of having lactose intolerance or malabsorption
13
Fructose
The presence of hydrogen in specific amounts in the breath.
n/a
- When patients with diarrhea are suspected of having fructose intolerance or malabsorption
Lower Gastrointestinal Endoscopy
Test Type
Testing For
ACG Recommendations
When it’s typically used in IBS
14
Colonoscopy
IBD, microscopic colitis, colon cancer, or polyps
Recommend against routine colonoscopy in patients with IBS symptoms who are younger than 45 years old without warning signs.
- Patients who are over 45 years old and are due for a colonoscopy
- Patients who have IBS with alarm symptoms
- Patients suspected of having microscopic colitis
Anorectal Tests
Test Type
Testing For
ACG Recommendations
When it’s typically used in IBS
15
Anorectal Manometry (ARM)
Possible pelvic floor disorders by measuring the anal and rectal muscle tone and strength.
‘We suggest that anorectal physiology testing be performed in patients with IBS and symptoms suggestive of a pelvic floor disorder and/or refractory constipation not responsive to standard medical therapy.’
- When a pelvic floor disorder is suspected
- Constipation that is not responsive to treatment
16
Balloon Expulsion Test (BET)
Tests for defecatory disorders by measuring the ability to evacuate a balloon that is meant to mimic stool.
‘We suggest that anorectal physiology testing be performed in patients with IBS and symptoms suggestive of a pelvic floor disorder and/or refractory constipation not responsive to standard medical therapy.’
- When a pelvic floor disorder is suspected
- Constipation that is not responsive to treatment
17
MRI
Provides a visual on pelvic floor motion and anal sphincter anatomy to assess disordered defecation.
n/a
- When a patient has a normal BET but has symptoms that indicate disordered defecation or structural injury.
Bile Acid Malabsorption Tests
Test Type
Testing For
ACG Recommendations
When it’s typically used in IBS
18
SeHCAT
Bile acids in the body
n/a
Not available in the US.
19
Stool Testing
A 48-hour stool collection that measures total bile acids in stool
n/a
- When IBS-D patients are suspected of having bile acid malabsorption
20
Fasting serum FGF19
Bile acid malabsorption (blood test)
n/a
- When IBS-D patients are suspected of having bile acid malabsorption
21
Fasting serum C4
Bile acid production (blood test)
n/a
- When IBS-D patients are suspected of having bile acid malabsorption
Sucrase-Isomaltase Tests
Test Type
Testing For
ACG Recommendations
When it’s typically used in IBS
22
Duodenal Biopsies
Enzyme activity
n/a
- Generally used in patients with IBS-D/M or similar symptoms
- Some insurance companies require this for reimbursement for enzyme therapy.
23
Hydrogen- Methane Breath Test
The presence of hydrogen and methane in specific amounts in the breath.
n/a
- Generally used in patients with IBS-D/M or similar symptoms
- In patients who have symptoms after meals and who have not responded to a Low FODMAP diet
24
C-Sucrose Breath Test
The presence of hydrogen in specific amounts in the breath.
n/a
- Generally in patients with a IBS-D/M diagnosis or similar symptoms
- In patients who have symptoms after meals and who have not responded to a Low FODMAP diet
25
SI Genetic Testing
Presence of mutated sucrase-isomaltase genes
n/a
- Generally in patients with a IBS-D/M diagnosis or similar symptoms
- Not frequently used and is costly.
Post-Infectious IBS
Test Type
Testing For
ACG Recommendations
When it’s typically used in IBS
26
Blood test for antibodies
Increased levels of anti-CdtB and anti-vinculin which are present due to an immune response to a gastrointestinal infection.
n/a
- Used in patients with either IBS-D or IBS-M who have a history of gastroenteritis previous to their IBS diagnosis.
- Available, but not widely used as more research is needed to establish validity.
Blood Tests
- Complete Blood Count (CBC)
- Complete Metabolic Panel (CMP)
- C-Reactive Protein (CRP)
- Erythrocyte Sedimentation Rate (ESR)
- IgA anti-tissue transglutaminase (anti-tTG) + Quantitative serum IgA
- IgA Endomysial antibody (EMA)
- HLA-DQ2/DQ8 haplotype testing
Complete Blood Count (CBC)/Complete Metabolic Panel (CMP)
Your CBC and CMP are lab sets that are ordered at yearly checkups and are relatively inexpensive. The CBC order set contains several labs like your red blood cell count, white blood cell count, platelets, etc. The CMP tests for things like glucose, proteins, and electrolytes in your blood. There is currently no recommendation from the ACG on ordering these labs in IBS patients.2 These labs are usually most helpful when IBS patients present with alarm symptoms (Reference below). For example, if there is blood in your stool, your doctor may want to order a CBC.
C-Reactive Protein (CRP) & Erythrocyte Sedimentation Rate (ESR)
CRP and ESR are inflammatory markers and can help rule out IBD in patients with IBS-D symptoms. CRP and ESR tests alone cannot diagnose or rule out disease, and CRP may be better than ESR when testing to differentiate between IBD and IBS. The ACG recommends checking CRP along with fecal calprotectin (or lactoferrin) to rule out IBD2.
Immunoglobulin A Tissue Transglutaminase (IgA TTG) & Quantitative Serum IgA
IgA TTG and quantitative serum IgA are antibodies found in patients with Celiac Disease (CD). This test is only accurate if those being tested are eating gluten. If you have CD and you’re not eating gluten, your body won’t make the antibodies the tests are trying to detect3. People with IBS symptoms, especially those associated with IBS-D, may have a higher chance of having CD.2 The ACG recommends screening for CD by checking IgA TTG and quantitative IgA levels.2 These two blood tests alone cannot diagnose CD but aid in the diagnostic process. IgA TTG testing has low rates of false positives and false negatives4.
IgA Endomysial Antibody (EMA)
EMA is an antibody found in most (but not all) patients with CD. Since this is an antibody test, eating gluten while being tested is essential to achieve an accurate test result. This test is used in the diagnostic process for CD.4 EMA testing is expensive and usually used in patients that are difficult to diagnose3.
HLA-DQ2/DQ8 Haplotype Testing
This is a genetic test used in the diagnostic process for CD. This test cannot confirm that you have CD, but if you are a carrier of these genes, it means you have an increased risk of having or developing CD (from a 1% chance to 3% chance). If you do not carry this gene, it rules out having CD. Since this is a genetic test rather than an antibody test, it isn’t required to eat gluten for an accurate test result3.
Key Takeaways
- CBC and CMP are routine labs your doctor may order to rule out organic diseases in the presence of alarm symptoms in patients with IBS.
- CRP and ESR are inflammatory markers that are helpful in the diagnosis of IBD alongside fecal calprotectin or fecal lactoferrin.
- There are antibody tests that can help rule out Celiac Disease, but for accurate results, the tested person must be on a gluten-containing diet.
- HLA-DQ2/DQ8 are genetic tests that can help diagnose Celiac Disease in people who are not following a gluten-free diet.
Stool Tests
- Fecal calprotectin and fecal lactoferrin
- Enteric pathogens
Fecal Calprotectin & Fecal Lactoferrin
Fecal calprotectin (fCal) and fecal lactoferrin (FL) are inflammatory markers found in stool. These tests can be used to rule out IBD in patients with IBS symptoms. They are more accurate than other tests (like ESR or CRP) when trying to differentiate between IBD and IBS. In practice, fCal may be used more frequently than FL because fCal has more evidence in its ability to differentiate between IBS and IBD, and high levels of FL have also been associated with IBS2. The combination of testing CRP with fCal or FL can provide a clearer picture for whether or not you have IBS vs IBD. The ACG recommends that either fecal calprotectin or fecal lactoferrin be checked (with CRP) in patients without alarm symptoms who have diarrhea and suspected IBS2.
Enteric Pathogens
There are times when IBS can develop after a GI infection. This is generally referred to as post-infectious-IBS (PI-IBS). The infection could be bacterial, parasitic, or viral. The ACG recommends against stool testing for GI infections in patients with IBS unless there is a high risk of having Giardiasis, a parasitic infection. Testing for and treating bacterial or viral infections does not prevent the development of PI-IBS, and antibiotic use may be a risk factor for developing post-infectious IBS. Additionally, those with a parasitic cause of GI infection are more likely to develop PI-IBS than those with a bacterial or viral infection2. You are considered to be at high risk of Giardia exposure if you live in or are traveling in developing countries, have poor water quality, are camping, or have daycare exposure2.
Key Takeaways
- Fecal calprotectin and fecal lactoferrin are inflammatory markers indicative of IBD when found in certain amounts in the stool.
- It is recommended that fCal and FL be checked with CRP (a blood test) to more accurately diagnose/rule out IBD.
- It is not recommended to test stool for enteric pathogens unless the individual is at high risk of exposure to Giardiasis.
Breath Tests
Breath tests are not used to diagnose IBS, but rather to diagnose things like carbohydrate intolerance, small intestinal bacterial overgrowth (SIBO), and intestinal methanogen overgrowth (IMO).56 These conditions share symptoms and sometimes overlap with IBS. Breath tests are not necessary for everyone with IBS symptoms. Your doctor will decide what tests you need based on your history and symptoms. A meta-analysis showed that IBS patients were 3x more likely to have an abnormal breath test in comparison to someone without IBS7. Studies on breath tests have had varying results because of a lack of standardization regarding when to use them, how to prepare them, which ones to use, and how to interpret the results.6 This has recently improved, and there are now some guidelines on breath tests68. However, the clinical usefulness of these tests are still somewhat debated. Breath tests have a possibility of false positives due to increased transit time (meaning things are moving quickly) through the gut in patients with functional bowel disorders9. Another issue is their lack of repeatability of test results10. When taking a breath test, your doctor will give you a list of instructions for prep like fasting beforehand and avoiding antibiotics and exercise. For the test, you will ingest a measured dose of carbohydrate (lactose, fructose, lactulose, etc) and exhale into a container of some sort over several hours. The test is measuring gas that you exhale, like hydrogen or methane. Humans don’t produce these gasses, so when they’re detected in your breath in specific amounts, it means your gut bacteria (or archaea) are fermenting the carbohydrates you’ve eaten. When your gut bacteria ferments carbohydrates, it produces hydrogen gas. The gas is able to leave the gut through absorption in the bloodstream, where it gets transferred to the lungs and exhaled869. The breath tests that often get discussed with IBS:
- Lactulose hydrogen breath test
- Glucose hydrogen breath test
- Methane breath test
- Lactose breath test
- Fructose breath test
Lactulose Hydrogen Breath Test
The lactulose hydrogen breath test is used in diagnosing SIBO. For this test, your hydrogen levels will be measured after ingesting a dose of lactulose. This test has been criticized for high rates of false-positive values8 caused by the rapid transit of lactulose to the colon, where it gets fermented9. Still, the ACG recommends testing for SIBO using the lactulose hydrogen breath test in patients with IBS due to the overlap between those with IBS and SIBO68. The lactulose hydrogen breath test has been shown to help differentiate between IBS patients who have responded positively to rifaximin treatment (an antibiotic used in treating SIBO and IBS) versus those who have not211.
Glucose Hydrogen Breath Test
The glucose hydrogen breath test is used to diagnose SIBO by measuring hydrogen on the breath after taking a dose of glucose. Like lactulose, glucose can rapidly move to the colon, where it gets fermented, possibly resulting in false-positive tests for SIBO.98 However, some researchers say glucose is the preferred carbohydrate in diagnosing SIBO in non-surgical patients because its rate of false positives is lower than the lactulose hydrogen breath test.9 The glucose hydrogen breath test is another test that the ACG recommends using in patients with IBS who are suspected of having SIBO68.
Methane Breath Test
Testing for methane is similar to the glucose or lactulose hydrogen breath test. You’ll either take glucose or lactulose and instead of measuring hydrogen, your methane levels will be measured. A positive breath test for methane indicates intestinal methanogenic overgrowth (IMO)8, a condition seen most in IBS-C patients compared to other subtypes of IBS.12 The ACG recommends testing for methane to diagnose the overgrowth of methane-producing organisms (IMO) in symptomatic patients with constipation12.
Lactose Breath Test
The lactose breath test measures the hydrogen on your breath after ingesting a dose of lactose. This is to determine if you have lactose intolerance or lactose malabsorption13. There are no guidelines for testing patients with IBS for lactose malabsorption214. Breath testing can have limited accessibility, so alternatively, attempting an elimination diet where you cut out lactose may be the easiest way to test for symptom improvement14.
Fructose Breath Test
The fructose breath test measures the hydrogen on your breath after ingesting a dose of fructose. This test is to aid in diagnosing fructose intolerance. Incomplete fructose digestion can exacerbate or contribute to IBS symptoms14. SIBO should be ruled out before a fructose breath test because SIBO can cause a false positive fructose breath test. False negatives can also occur under certain circumstances6. Fructose malabsorption happens in healthy people and people with IBS15. How you tolerate fructose seems to be dependent on a number of factors. And while the fructose breath test has shown some clinical relevance, there’s still a chance of you getting a false positive or false negative result16. Because of the variability in test results, it may be beneficial for people having symptoms associated with fructose intake to reduce high fructose foods in their diet. This includes things like apples, pears, juices, or beverages sweetened with high fructose corn syrup. A low FODMAP diet has also shown symptom improvement in those with fructose-related symptoms. However, any restrictive diet should be followed with the guidance of a registered dietitian.
Key Takeaways
- Breath tests involve the ingestion of a specific carbohydrate dose followed by measuring exhaled gas over several hours.
- The ACG recommends lactulose and glucose hydrogen breath tests in diagnosing SIBO despite the possibility of false positives.
- The ACG recommends the methane breath test in patients with constipation.
- Carbohydrate malabsorption or intolerance may play a part in exacerbating IBS symptoms or could be the origin of symptoms.
- There are no guidelines in using breath tests for carbohydrate malabsorption or intolerance in IBS patients at this time.
- Reducing the amount of lactose or fructose in the diet or trialing a low FODMAP diet under the guidance of a registered dietitian is a way to seek symptom improvement without a breath test that may give inaccurate results.
Lower GI Endoscopy
Colonoscopy
A colonoscopy is a test used to investigate other potential causes for IBS symptoms such as IBD, microscopic colitis, or colon cancer. This test is generally costly and inconvenient. Having or being suspected of having IBS is not enough to require a colonoscopy. The ACG recommends against routine colonoscopies in patients with IBS symptoms younger than 45 years old unless they have alarm symptoms. People who may benefit from a colonoscopy are those with alarm symptoms in conjunction with their IBS symptoms, people who have IBS and are due for a colonoscopy because of their age, and people suspected of having microscopic colitis214.
Key Takeaways
- A colonoscopy is not needed in all IBS patients
- IBS patients who may require a colonoscopy include patients who are over 45 years old and are due for a colonoscopy, patients who have IBS with alarm symptoms, and patients suspected of having microscopic colitis.
Anorectal Testing
These tests determine if you have anorectal dysfunction. Anorectal disorders include fecal incontinence, functional anorectal pain, or functional defecation disorders like dyssynergic defecation. Anorectal dysfunction can be caused by several things like pelvic floor disorders or IBS.172 Anorectal disorders occur in all subtypes of IBS, but the prevalence among IBS patients is unknown. The ACG suggests anorectal testing in those with IBS whose symptoms suggest pelvic floor disorders and patients with constipation that do not respond to standard treatment2. Your doctor may recommend anorectal testing since people with IBS may also have an anorectal disorder. An example of this possible overlap is dyssenergic defecation. To be diagnosed with dyssenergic defecation, you have to meet the criteria for IBS-C or functional constipation and have impaired stool evacuation shown by 2 of the 3 tests discussed below. Anorectal testing is not widely used because of limited availability and unestablished guidelines,2 but it can reveal abnormalities that can be treated by specific therapies like biofeedback2.
- Anorectal manometry (ARM)
- Balloon expulsion test (BET)
- Evacuation imaging via MRI
ARM
To put it plainly, this test involves a doctor inserting a balloon with an attached tube into your rectum. The tube is attached to a machine that fills the balloon with air. From here, your doctor will measure mechanisms used when you pass stool, like your resting anal pressure, squeezing pressure, etc17.
BET
Like the ARM, a balloon is inserted into the rectum and filled with air or water. This test measures the time required to expel the balloon. This can range from 1-2 minutes for a balloon filled with 50-mL of water. This test can help screen for defecation disorders but isn’t always accurate because a balloon may not totally mimic the patient’s stool17.
MRI
An MRI can visualize the anal sphincter anatomy and all pelvic floor motion. An MRI may be helpful in patients with a normal balloon expulsion test to identify structural injuries or disordered defecation17.
Key Takeaways
- Anorectal disorders share symptoms with IBS and may overlap
- The ACG suggests anorectal testing in patients with IBS whose symptoms suggest pelvic floor disorders and patients with constipation that do not respond to standard treatment.
- Tests used to diagnose anorectal disorders include an anorectal manometry (ARM), the balloon expulsion test (BET), and an MRI.
- ARM and BET involve a balloon being inserted into the rectum and taking different measurements.
- MRIs give an image of the pelvic area and can help confirm structural injuries or pelvic floor disorders.
Bile Acid Malabsorption
Bile acid malabsorption (BAM) is when your body cannot reabsorb enough bile acids in the small intestine, specifically in the terminal ileum. From the small intestines, bile acids then enter the colon, where they get exposed to colonic flora leading to the production of secondary bile acids, which can increase fluid secretion, resulting in diarrhea. Diarrhea caused by BAM may contribute to symptoms in some people diagnosed with IBS-D.2 Unfortunately, testing for BAM is not widely available, and research is still needed to confirm the validity of some testing methods14. Testing for bile acid malabsorption includes:
- Selenium (Se)-homocholic acid taurine (SeHCAT)
- Stool testing in BAM
- Blood testing in BAM
SeHCAT
This test involves monitoring radiolabelled bile acids with 2 body scans. 18This is the most definitive test for BAM and is unavailable in the US. The test is available in some European countries but is used infrequently due to the required infrastructure and time necessary to perform the testing142.
Stool Testing
Stool testing for BAM involves a 48-hour stool collection to measure the total amount of bile acid. One study showed that patients with IBS-D had significantly higher bile acid content in their stool in comparison to healthy individuals or those with IBS-C.219 In other words, those with IBS-D may benefit from BAM stool testing.
Blood Testing
There are two serum markers that may help identify patients with BAM, but accessibility is limited, study results are mixed, and further research is needed21920.
- Fibroblast growth factor 19 (FGF19): is involved in decreasing bile acid synthesis, and a low fasting serum level may indicate BAM20.
- Serum C4 is a direct measure of bile acid production. A higher level is indicative of BAM and has been seen in patients with IBS-D in comparison to those with IBS-C or healthy people20.
Key Takeaways
- Bile acid malabsorption can contribute to symptoms in some IBS-D patients.
- Stool testing for bile acids is the most reliable test available in the US.
- Blood tests for bile acid malabsorption are available and may help diagnose BAM, but access is limited.
Sucrase-Isomaltase Deficiency
Sucrase-isomaltase is an enzyme produced in the small intestine and helps digest sucrose and starches which account for more than 60% of ingested carbohydrates in Western diets21. When this enzyme is deficient, sucrose and starches are not able to fully digest. This results in a number of symptoms like abdominal pain and cramping, bloating, gas, and osmotic diarrhea after ingesting a meal.2122 This is kind of similar to lactose intolerance–people cannot digest lactose because they lack the enzyme lactase required for digestion. Sucrase-isomaltase deficiency (SID) can be due to genetic variations in what are called ‘sucrase-isomaltase (SI) genes.’ SID can also be caused by intestinal damage that occurs from infections (like Giardiasis), SIBO, Crohn’s disease, ulcerative colitis, etc. SID resulting from a genetic variation is lifelong, where SID from a secondary cause (like Crohn’s disease) could resolve once that secondary cause was under control or cured22. People who presumably have IBS-D/M or who have symptoms like diarrhea, bloating, and gas and who do not respond to typical IBS treatments or a low FODMAP diet may consider getting tested for SID since it has been shown that people with these symptoms might have SID21. Tests for SID are available but imperfect in that they are either costly or lack proper validation. Some of the more common testing methods for SID include:
- Duodenal Biopsies
- Hydrogen Methane Breath Test
- C-Sucrose Breath Test
- Sucrase-Isomaltase (SI) Genetic Test
Duodenal Biopsies
An esophagogastroduodenoscopy (EGD) is required to obtain biopsies (aka, tissue samples) from the duodenum (a part of your small intestine). For the EGD, you will be sedated, and a tube will be placed down your throat and into your small intestines. During the EGD, they usually try to get several biopsies from your duodenum. The biopsies help to diagnose SID by assessing enzyme activity. They can also help differentiate between secondary cases of SID from inherited deficiencies. This test is currently considered the ‘gold standard’ for diagnosing SID. It is costly and invasive, but some insurance companies require it in order to reimburse for sacrosidase. The accuracy of test results can depend on the handling of the biopsies afterward, as well as if the biopsies were taken from the correct part of the small intestine232422.
Hydrogen Methane Breath Test
For this test, someone suspected of having SID would ingest a dose of sucrose and have their hydrogen and methane levels measured over a number of hours. Like other breath tests, results can be compromised by contamination from a number of factors like SIBO, recent antibiotic use, or increased transit time. This can lead to either false-positive or false-negative results. A downside to this test is that the dose of sucrose that’s required is a pretty hefty dose and can cause severe symptoms in patients with SID22.
13C-Sucrose Breath Test
The 13C-Sucrose breath test helps determine if you are able to digest sucrose. For this test, you will ingest a form of sucrose called 13C-sucrose. Instead of measuring hydrogen or methane, a gas called, 13CO2 is measured in your breath. This test has shown to be more tolerable to people with SID in comparison to the hydrogen-methane breath test, as the dose of 13C-sucrose is smaller in comparison to the sucrose dose in the hydrogen-methane breath test. However, this is a newer test and it has not been validated2422.
SI Genetic Test
At least 37 mutations in the SI gene have been found. The mutations affect various aspects of gene function, which results in varying degrees of enzyme activity. For example, sucrase activity in patients with SID can range from absent to low activity, while isomaltase activity can range from absent to normal. While genetic testing is helpful, it is costly and doesn’t completely rule out SID with a negative test. This is because not all genetic mutations have been identified and because it doesn’t capture the people who have SID due to secondary causes. However, a positive test confirms that SID is present2224.
Key Takeaways
- Sucrase-isomaltase deficiency (SID) makes it difficult to digest sucrose and some starches.
- Testing for SID is imperfect, with some tests being costly and others being invalidated.
- A duodenal biopsy is the gold standard for diagnosing SID, but is costly and invasive.
- The sucrose dose required for the hydrogen-methane breath test can often cause symptoms in people with SID.
- The 13C-Sucrose breath test is a better tolerated breath test, but is not validated.
- Genetic testing for SID is available but cannot capture the acquired version of SID or genetic variations that have not been identified.
Post-Infectious IBS
There are two antibody tests that are being studied as potential IBS biomarkers for post-infectious IBS. Now when you hear the word ‘antibody’ think of your immune system sending out a defensive line (aka antibodies) to fight off something that’s been deemed a threat. The antibodies being researched are:
- Anti-cytolethal distending toxin B (anti-CdtB)
- Anti-vinculin
Anti-cytolethal Distending Toxin B (anti-CdtB) & Anti-vinculin
It’s believed that the offending pathogen from a GI infection releases a toxin called cytolethal distending toxin B (CdtB). In reaction to this, your body generates an antibody, called anti-CdtB, to battle that toxin. CdtB is molecularly similar to vinculin, a protein that’s in your epithelial cells. Because of this molecular similarity, your body thinks your vinculin is out of whack, and therefore, is essentially tricked into making antibodies against vinculin (called anti-vinculin)25. The research for these antibodies being a valid biomarker for PI-IBS has had mixed results. One study showed that the antibodies in IBS-C patients matched healthy controls25, while another study showed that IBS-C patients had the highest levels of antibodies26. The studies in IBS-D have been somewhat more consistent. The largest study done included 2375 test subjects and showed that IBS-D patients had higher antibody levels than healthy controls and patients with IBD and Crohn’s disease27. Studies from Mexico28 and Egypt29 have also shown that patients with IBS-D have higher antibody levels. On the other hand, a study out of Europe was unable to differentiate between IBS-D patients and healthy controls while comparing antibody levels26. Similarly, a study out of Australia showed that IBS-D patients had similar anti-vinculin levels to healthy controls30. So in summary, the theory is that after a GI infection, higher levels of anti-CdtB and anti-vinculin could be detectable in a blood test in some PI-IBS patients, especially those with diarrhea symptoms. These antibody tests are currently available, but should be used with caution as they have a high chance of delivering a false negative result and have not been validated. (Reference Below) The idea of a biomarker for IBS is intriguing, but there is still more research needed to confirm that these tests can confidently distinguish between who has IBS vs some other disease. For now, we’re not quite ready to call them true biomarkers, but with more research, we may change our minds.
Key Takeaways
- There are two antibodies being researched as potential biomarkers in people with post-infectious IBS (PI-IBS) called anti-cytolethal distending toxin B (anti-CdtB) and anti-vinculin.
- The research conducted has shown mixed results, and additional research is needed before these tests can be recommended as legitimate biomarkers for PI-IBS.
Allergy Tests
Up to 50% of patients with IBS have been shown to report an adverse reaction to food, meaning an allergy, intolerance, or sensitivity. Most adverse reactions to foods are food intolerances or sensitivities, rather than a true allergy. In the general population, 20% of people report adverse reactions to food, but only 2-3% of those people have recurrent symptoms when eating that same food again. The ACG recommends against testing for food allergies or sensitivities in patients with IBS unless there are reproducible symptoms that indicate a concern for a true food allergy2. According to a study, people with IBS do not have a higher rate of food allergies than the general population. In addition, allergy tests have been shown to have low specificity, meaning the tests may give a high rate of false positives2. You can find a number of testing products that are marketed as diagnosing food sensitivities or intolerances; however, most of them have not gone through proper clinical trials or been validated. For example, serum IgG panels are often seen online but have not been validated and are not clinically recommended312.
Key Takeaways
- People with IBS have more adverse reactions to food than the general population but do not have a higher rate of true food allergies.
- The ACG only recommends that patients with IBS get food allergy tests if there are reproducible symptoms when eating specific foods.
- Allergy tests have a low specificity, which could give a high rate of false positives.
- Tests for sensitivities or intolerances, like the serum IgG test, have not been validated and are not clinically recommended.
Intestinal Permeability Tests
Increased intestinal permeability (sometimes referred to as ‘leaky gut’) has been identified in certain IBS populations, but the scientific community is still trying to sort out if permeability changes are a cause or consequence of the underlying disease state.
Currently, the ACG has no recommendations for testing intestinal permeability in clinical practice for IBS management.
At this time, we do not recommend permeability testing for several reasons, including:
- A lack of standardized testing methods
- A lack of standardized normative testing values – i.e., values which determine the degree of permeability that’s normal or pathological
- The cost, potential invasiveness, impracticality, or time intensiveness of the tests
- A lack of well-validated treatment options for increased permeability
- Sparse evidence that intestinal permeability improvements alter the underlying disease state or symptoms
We’re giving permeability testing a brief mention here because, although far from perfect, they have been widely used in IBS populations in scientific literature and research. We will review both orally ingested probes and common blood tests that are thought to measure permeability. And while we don’t recommend these tests just yet, this is an evolving area of research that may someday bring new therapeutic options to the table for IBS management. In the meantime, any permeability test results should be interpreted with caution.
Orally Ingested Probes
The most common method researchers use to test permeability in human subjects are orally ingested probes. Translation? You down a drink that contains some sort of molecules that are later measured in your urine. Various types and sizes of probes are used in these tests. Commonly used molecules include sugars such as lactulose, mannitol, sucrose, sucralose, and rhamnose; however, other types of non-sugar probes such as polyethylene glycols (PEG) and chromium-ethylenediaminetetraacetic acid (51Cr-EDTA) are also used3233. Unfortunately, there are several problems with these orally ingested probe tests that makes interpreting individual results difficult, at best. One such issue is that test results may be unreliable because certain foods or cosmetics contain some of the same molecules that are being used in these tests. This is especially true when it comes to mannitol.33 Because of this, more recent studies are using a different form of mannitol, called 13C-mannitol, that is less prone to contamination issues when performing the lactulose/mannitol test.32 Other issues include a lack of standardization and validation of testing methods, as well as insufficient data on normal values323435.
Blood Tests
Another way in which intestinal permeability is measured is through blood tests. Researchers have used several blood tests, however, some of the most common tests include zonulin, lipopolysaccharide (LPS), and intestinal fatty acid binding protein (I-FABP). And like with the orally ingested probes, many factors can affect these blood tests that make them unreliable measures of permeability. For example, the molecule zonulin has been tied to increased permeability due to its actions on tight junctions between intestinal cells. But one significant challenge with this test is that zonulin was initially identified as a compound called pre-haptoglobin2, and recent research suggests commercially available tests don’t actually measure pre-haptoglobin2.36 The reason for this is likely because zonulin itself is more complex and consists of a variety of structurally and functionally similar peptides in the zonulin family.37 Given that we don’t have a clear picture of what exactly these tests are measuring, or how these other peptides relate to permeability, we have to be cautious with using zonulin as a biomarker for permeability. Similar issues arise when it comes to using LPS as a measure of permeability. LPSs are large molecules found in the outer membrane of bacteria. Circulating LPS in the blood is thought to increase as a result of increased intestinal permeability.38 The problem is that LPS may enter the bloodstream from several other sources outside of the GI tract (i.e., infected body tissues, the blood itself, the respiratory tract, or food).38 Because of this, we can’t say with certainty that circulating LPS is always a result of increased intestinal permeability. Another suggested marker of permeability is I-FABP, a type of cellular protein that can be detected in the blood after intestinal injury.33 Preliminary evidence suggests that I-FABP may be a useful blood marker for increased permeability, as some studies have shown that it correlates well with other measures of permeability.39 I-FABP may be a potential biomarker of intestinal barrier dysfunction,33 however this research is still in its infancy and more validation studies are needed.
Key Takeaways
- Gut permeability testing has been used in scientific literature and research, but these tests have yet to be fully standardized and validated.
- Commonly used tests include orally ingested probes that are taken by mouth and later measured in the urine, as well as several types of blood tests
- Based on the research available, we don’t currently recommend permeability testing and any test results should be interpreted with caution.
