IBS/SIBO

Question 1

where is prdxn of organic acids

Answer 1

terminal ileum and ascending colon

Question 2

benzoate

Answer 2

■ Produced by bacterial metabolism of dietary polyphenols.
○ If elevated with no other markers, may just indicate high dietary intake
of polyphenols.
■ Elevation can be a marker of bacterial overgrowth or impaired phase 2 detox capacity due
to glycine and/or pantothenic acid insufficiency.
■ High benzoate can also be caused by ingestion of a benzoic acid, which is found in
processed and packaged foods like pickles, soda, or lunch meats, or naturally in foods
like cranberries.
■ Often elevated in conjunction with hippurate, which is a normal byproduct of
benzoate metabolism.

Question 3

phenylacetate

Answer 3

• Byproduct of intestinal action on polyphenols, tyrosine, or phenylalanine.
  ○ Normally present in low concentrations
  ● Phenylketonuria (PKU), an inherited disorder that leads to accumulated PAA levels.
  ○ Can lead to neurotoxicity and brain damage
  ● In most patients there is slight elevation, which is indicative of microbial overgrowth.
  ○ High levels should be referred to an inherited disease specialist

Question 4

phenylpropionate

Answer 4

■ Byproduct of intestinal action on polyphenols and phenylalanine.
■ Metabolized by medium-chain acyl-CoA dehydrogenase (MCAD) and normally not in urine.
■ Very high levels indicate MCAD deficiency.
■ Signs and symptoms (vomiting, lethargy, hypoglycemia) occur early in childhood.
■ Mild elevation is a sign of microbial overgrowth.
■ Refer out for very high levels.

Question 5

P-hydroxybenzoate

Answer 5

-From bacterial metabolism of polyphenols and tyrosine.

■ Elevations indicate microbial overgrowth, especially E. coli.

Question 6

P-hydroxyphenylacetate

Answer 6

■ From bacterial metabolism of tyrosine.
■ Useful in detecting small bowel disease caused by overgrowth of anaerobes.
■ Very high in patients with cystic fibrosis or other conditions that impair amino acid absorption.

Question 7

indican

Answer 7

■ From bacterial metabolism of tryptophan.
■ Elevations indicative of bacterial overgrowth in upper small bowel.
■ Can help differentiate pancreatic insufficiency from biliary stasis as a cause of steatorrhea
(fatty stools).
○ High indican → pancreatic insufficiency
○ Normal indican → biliary stasis
■ Can also signify low stomach acid since incomplete protein digestion can cause elevations.

Question 8

tricarballylate

Answer 8

■ Produced by aerobic bacteria.
■ Extremely high affinity for magnesium, preventing magnesium absorption.
■ When elevated, supplementation with magnesium in addition to gut treatment is necessary.

Question 9

D-lactate

Answer 9

Major metabolic byproduct of beneficial bacteria species in the gut like Lactobacillus acidophilus.
○ Different isomer of lactic acid than the ones produced during exercise.
■ Elevated in cases of carbohydrate malabsorption, which allows L. acidophilus to flourish.
■ Lactobacillus species are common in probiotics; best to avoid these when D-lactate
is elevated.
○ Red flag for SIBO if patient gets worse with these probiotics.
■ Symptoms include GI distress and neurological and cognitive symptoms.

Question 10

3,4-dihydroxyphenylpropionate (#,4-DHPP)

Answer 10

■ Produced by Clostridia species and elevated in overgrowth.
■ Can lead to increased dopamine due to inhibited dopamine metabolism/breakdown.
○ Potential neurologic symptoms, as well as mood and behavioral problems.

Question 11

D-arabinitol

Answer 11

-Metabolite of most pathogenic Candida species.
○ One of the most sensitive markers for invasive candidiasis.
■ A better indicator for fungal overgrowth than blood cultures.

Question 12

3 primary processes that contribute to SIBO

Answer 12

1. Gastric acid secretion
   a. Low stomach acid in particular. This is because stomach acid suppresses the growth
   of ingested bacteria.
2. Small intestine dysmotility
   a. Disruption of the migrating motor complex and the peristaltic wave in the gut,
   which normally has a cleansing action and prevents the overgrowth of bacteria.
3. Disrupted gut microbiome
   a. Dysbiosis in the colon that leads to overgrowth of bacteria in the small intestine.
   b. It is well-established that antibiotic use can lead to disrupted gut microbiome and
   in turn SIBO.

Question 13

complications of SIBO

Answer 13

malabsorption, nutrient deficiency, metabolic bone disorders, and small
intestine inflammation.
For example, SIBO is known to cause B12 deficiency because B12 is absorbed in the small intestine.
In addition, SIBO can lead to fat malabsorption. This can lead to a decline in fat-soluble vitamin
absorption, which leads to low vitamin D and low vitamin K2, which can cause osteoporosis. Also,
vitamin A deficiency can lead to night blindness and retinopathy. In addition, patients may have
prolonged clotting times due to vitamin K deficiency.

Question 14

2017 SIBO North American Consensus

Answer 14

An increase in hydrogen greater than or equal to 20 parts per million before 90 minutes is
positive.
○ The “double peak” has no validity and should not be used.
○ A rise in hydrogen that occurs after 90 minutes is not a positive result.
■ A methane level greater than or equal to 10 parts per million at any point during the test is
considered positive for methane.

Question 15

glucose vs lactulose for SIBO

Answer 15

Glucose is absorbed in the proximal small intestine and the duodenum, so if overgrowth of bacteria
is occurring in the jejunum or ileum, you may get a false negative. Lactulose is not absorbed at all
in the small intestine. It is fermented by bacteria in the colon.
The issue with lactulose as a substrate is that the lactulose breath test is based on the idea that
orocecal transit time, or the amount of time it takes for a substance to go from the mouth to the
cecum, which is the first part of the colon, in healthy people is always 90 minutes.
However, there’s a problem with this because studies have shown that orocecal transit time in
healthy people averages from 72 to 85 minutes. Further complicating this problem is that lactulose
has a laxative effect. It accelerates transit time, so even someone who normally has an orocecal
transit time of 90 minutes, if they take lactulose, it might reach the colon in less than 90 minutes,
and that could generate a false positive.
Despite its drawbacks, Chris prefers lactulose substrate because potential benefits of treatment,
coupled with the general safety of the treatment interventions outweigh the potential risk undertreating with a false negative. However, the risk of a false positive is that you may miss other
underlying issues. If the patient is treated and does not improve, you should reconsider whether
there might be something else going on that is driving the bacterial overgrowth

Question 16

high risk of false positive SIBO breath

Answer 16

diarrhea, young children, Crohns, celiac, laxatives, prokinetics

Question 17

high risk for false negatives SIBO breath

Answer 17

constipation, elderly, gastroparesis, PPI, opiates

Question 18

Pimentel Revised criteria

Answer 18

Any rise in hydrogen before 90 minutes or any rise of more than 20 ppm over the course of
180 minutes of measurement.
○ The magnitude of abnormal rise under 90 minutes not specified, but Pimentel
stated later that most patients had a rise of 20 parts per million or more within that
first 90-minute period.

Question 19

what could indicate 0 hydrogen and 0 methane on breath test

Answer 19

There is production of other types of gases that aren’t measured by this test.
a. Studies show that patients with lower methane production, like zeros here, can
have higher concentrations of sulfate-reducing bacteria, and the product of sulfate
reduction is hydrogen sulfide. Hydrogen sulfide should be removed by first-pass
detoxification in the liver, but if detox mechanisms are impaired, the hydrogen
sulfide can accumulate in the small intestine and the colon.
b. The sulfate-reducing bacteria consume all of the hydrogen that would normally
have been produced by bacteria, and there’s nothing left for methanogens to
consume, so the methanogens get starved out. This results in zero for both
hydrogen and methane levels.
Currently, if we see these zeros and if the patient has a lot of signs and symptoms of SIBO, then we
will generally do a therapeutic trial and treat them and see how they respond.

Question 20

klebsiella

Answer 20

■ Can be a normal resident of the digestive tract but can become overgrown in dysbiosis.
■ Associated with joint pain, conditions like ankylosing spondylitis, reactive arthritis, and
rheumatoid arthritis.
■ Also reported in irritable bowel syndrome and other gut issues.
■ When you see a positive result for Klebsiella, especially in someone with joint pain, you
should run the HLA-B27 test.
■ Ankylosing spondylitis patients have elevated levels of antibodies to Klebsiella. The theory
is this is due to molecular mimicry.
■ Only a small percentage of people with the HLA-B27 gene develop ankylosing spondylitis,
which suggests there may be an environmental trigger.
■ Some of the literature is now looking at the effectiveness of a low-starch diet for people
who have Klebsiella and HLA-B27.
■ You may want to use antimicrobials and recommend a low-starch diet for these patients.

Question 21

H pylori

Answer 21

Associated with stomach and duodenal ulcers
■ Possibly increase the risk of gastric cancer
H. pylori: pathogen or not?
1. Dr. Martin Blaser gathered evidence suggesting that H. pylori is not always harmful. It may
even be helpful in some circumstances. Dr. Blaser’s research shows that H. pylori has
beneficial functions that actually begin in infancy, if a baby acquires it. For example, it
appears to protect against the development of allergies and asthma.
2. In animal studies, if the animals are infected early on in life, such as shortly after birth or
during infancy, H. pylori has been shown to play a protective role.
3. Another factor determining the pathogenicity of H. pylori is the particular strain. Some
strains of H. pylori appear to be more pathogenic than others

Question 22

yeast and fungi

Answer 22

Normal residents of the digestive tract, but they can be a problem if they are overrepresented.
■ Fungi secrete toxins that can damage the intestinal lining and provoke inflammation. They
compete for adhesion sites with beneficial bacteria. They are hyphaic and can puncture the
gut lining and make it permeable.
■ Some species of Candida secrete substances which have SigA protease activity. This means
that the Candida can secrete toxins that can break down secretory IgA.
■ You’ll often see low SigA in patients with fungal overgrowth.
In DD CAPS x3, yeast are evaluated via two methods:
1. Yeast culture
a. Can get a false negative as yeast have a patchy distribution in stool.
b. Anything 2+ or above in the dysbiotic column would be considered a problem.
2. microscopic examination
a. “None” or “rare” is the expected finding for microscopic yeast.
b. “Few,” “moderate,” or “many” indicates fungal overgrowth.
3. The above results show a 3+ for Saccharomyces boulardii in the yeast culture.
■ If the patient is taking this as a supplement, it’s not pathological, and it doesn’t
require treatment.
■ This is true even if you see a positive finding under the microscopic section because it
could just be referring to the Saccharomyces boulardii.

Question 23

pH on stool

Answer 23

Strong correlation between acidic environment and fungal overgrowth.
Too alkaline can create an environment that is conducive to overgrowth of harmful bacteria

Question 24

blastocystis

Answer 24

Most common parasite in North America.
○ May be a normal resident of the gut. DNA/PCR studies have found Blastocystis in
80% of healthy individuals.
Several factors determine whether it will be benign or pathogenic in a given individual.
■ Likely nonpathogenic in healthy hosts
Our gut is an ecological system. If it’s healthy, it’s resistant to pathogens, and if it’s
not, it will be susceptible to pathogens.
■ Pathogenic in people with underlying health conditions.
■ Multiple types of Blastocystis, some being more pathogenic.
○ No current testing for subtypes.
■ Treatment is not risk-free, so the decision to treat requires clinical judgment.
For example, if Blastocystis was positive in all three stool samples on a patient who felt great, had
no symptoms, hadn’t taken any antibiotics for 20 years, and was as healthy as could be, I would
definitely not recommend treatment.
However, if Blastocystis comes back positive on a patient with long history of digestive problems,
fatigue, eczema, acne, low libido, insomnia, and other symptoms, and if they are positive for other
parasites, then an antiparasitic protocol might be warranted.

Question 25

blastocystis sx

Answer 25

pain, gas, bloating, diarrhea, constipation, greasy stools, nausea, fatigue, skin rash, brain fog, joint pain

Question 26

dientamoeba fragilis

Answer 26

○ Very often a co-infection with pinworm.
○ Unclear if commensal or pathogenic.
○ Symptoms are similar to Blastocystis
○ If you find D. fragilis, consider further testing/treating for pinworm because that’s
how it’s often transmitted.

Question 27

endolimax nana

Answer 27

○ Nonpathogenic in immunocompetent people
○ Pathogenic in immunocompromised.
○ Common co-infection with Blastocystis.
○ If you see it on a test alone, there is concern of missing others; consider re-testing.
(Follow-up test with a specialized lab such as Parasitology Center)

Question 28

entamoeba coli

Answer 28

○ Generally considered to be nonpathogenic commensal parasite.
○ There are two concerns:
■ Often occurs with other pathogenic parasites.
■ Sometimes confused with Entamoeba histolytica (highly pathogenic).
○ If you see it on a test alone, consider re-testing, as there is concern of missing others.

Question 29

giardia

Answer 29

○ Immunoassays or antigen detection are preferred due to difficulty detecting in stool.
○ Universally considered pathogenic, so treat if detected.
○ Many associated complications.
These may persist even after eradication.

Question 30

cryptosporidium

Answer 30

Similar symptoms to other parasites, with watery diarrhea most common in the
acute phase.
○ Can be serious to life-threatening in immunocompromised patients.
○ Often self-limiting, but reinfection and chronic infection are possible.
○ Rare to find on Doctor’s Data.
○ Instead, the direct fluorescent antibody technique is the most sensitive and specific.
I most often see it as a positive antigen result on the BioHealth test.
○ Treat if detected.

Question 31

Charcot-leyden crystals

Answer 31

○ Evidence of eosinophil breakdown. Therefore, often seen in parasitic disease.
○ If you see them but no parasite, consider a re-test with a different lab to make sure
a parasite was not missed.

Question 32

RBC in stool

Answer 32

Associated with parasitic or bacterial infections.
○ Also associated with inflammatory bowel disease Crohn’s and ulcerative colitis.
○ Check for invasive gut pathogens like Shigella, Campylobacter, and Yersinia, which
can cause mucosal inflammation and bleeding.

Question 33

fecal elastase

Answer 33

○ Pancreatic enzyme that digests and degrades proteins.
○ Low indicates pancreatic exocrine insufficiency.
■ Moderate: 100-200
■ Severe: <100
○ Highly specific for small intestinal disease
○ Pancreatic insufficiency may be a risk factor for SIBO, especially recurring SIBO.

Question 34

fat stain

Answer 34

○ Indicator of fat malabsorption, which is often secondary to pancreatic or biliary
tract disease.
○ If you see positive fat stain consider: gastric surgery, pancreatic disease, biliary
obstruction, liver disease, or intestinal permeability.
○ Supplementation with pancreatic enzymes, HCL, and/or bile may be helpful.

Question 35

muscle fibers

Answer 35

○ Marker of incomplete protein digestion.
○ May also be seen with inadequate chewing.
○ Can suggest hypochlorhydria or insufficient enzyme production.
○ Digestive enzymes or HCl can be helpful.

Question 36

vegetable fibers in stool

Answer 36

○ Indicates carb malabsorption, which can be a risk factor or effect of SIBO.
○ Digestive enzymes or HCl can be helpful.

Question 37

lactoferrin

Answer 37

○ Protein in the transferrin family that’s expressed in activated neutrophils.
○ Significantly elevated lactoferrin is a marker for IBD.
○ Marker for gut inflammation/infection at lower levels.

Question 38

calprotectin

Answer 38

○ Marker of GI inflammation in the mucosa and presence of neutrophils.
○ May be more accurate for IBD diagnosis than lactoferrin.
<50 normal, 50-200 inflammation/inactive IBD, >200 CA or active IBD
If calprotectin>200 and lactoferrin>50, run IBD expanded antibody panel with
LabCorp (test #162045).

Question 39

fecal lysozyme

Answer 39

○ Lysozyme is an enzyme that catalyzes the hydrolysis of specific glycosidic bonds in
mucopolysaccharides that constitute the cell wall of Gram-positive bacteria.
○ General marker for gut inflammation.
○ Moderately elevated level associated with overgrowth or food antigens
○ Can be treated with anti-inflammatories or removing the offending agent.
○ High levels associated with IBD and non-IBD GI disease with diarrhea; often
requires further testing.

Question 40

sIgA

Answer 40

○ First line of defense against entry of enteric toxins and pathogenic organisms from
the colon.
○ Best used as a marker to determine outcomes of treatment.
○ Can take several months to normalize.

Question 41

WBC/mucus in stool

Answer 41

○ Occur with bacterial and parasitic infections and gut inflammation.

Question 42

SCFA

Answer 42

○ Produced by beneficial bacteria in the gut;
○ Are the end product of bacterial fermentation of fermentable carbohydrates.
○ Decrease the pH to make an unsuitable environment for pathogens.
○ Decrease inflammation and increase T-regulatory cell production/differentiation
○ Stimulate growth and repair of enterocytes, the cells lining the GI tract.

Question 43

what % of celiac have sx after GF diet

Answer 43

7-30% (2/2 cross reactivity)- Array 4 test

Question 44

paleo for vegetarian modifications

Answer 44

Vitamin B12
• Eat egg yolks, cheese, yogurt, or milk daily
• Optional: supplement with 1,000 mcg (1 mg) of sublingual methylcobalamin

• Calcium
• Eat two to three cups of leafy green vegetables daily, such as collards, turnip
greens, kale, broccoli, or bok choy (300 to 500 mg)
• Add in one to two tablespoons of blackstrap molasses daily (135 to 270 mg)
• Snack on figs (½ cup contains 120 mg of calcium)
• Consider eating bone-in canned fish like sardines and salmon (pescetarian)

• Iron
• Eat iron-rich plant foods
• Chard, collard greens, spinach, pumpkin, squash, pine nuts, pistachios,
sunflower seeds, cashews, unhulled sesame seeds, white potatoes,
chocolate
• Consume vitamin C-rich foods paired with non-heme iron-rich plant foods
• Spinach & lemon juice, lentils & tomatoes, kale & sweet potato, for example
• Consume one to two cups of legumes daily (especially lentils)
• Add in one to two tablespoons of blackstrap molasses daily
• Premenopausal women may need a supplement

• Omega-3 Fats (EPA/DHA)
• Consider eating bone-in canned fish like sardines and salmon (pescetarian)
• Supplement with Extra Virgin Cod Liver Oil or Vegan Omega-3s

• Vitamin A
• Consider supplementing with vitamin A from Extra Virgin Cod Liver Oil
(pescetarian)
• Eat plenty of red, orange, yellow, and green plant foods
• Do not supplement with beta-carotene

• Vitamin D
• Get 30 minutes of sun exposure daily
• Supplement in winter with 2,000 IU vitamin D3
• Zinc
• Eat sesame seeds, pumpkin seeds, lentils, chickpeas, and cashews
• Consider supplementing with 15 mg daily

Question 45

paleo for vegan modifications

Answer 45

● Vitamin B12
○ Supplement with 1,000 mcg (1 mg) of sublingual methylcobalamin

● Calcium
○ Eat two to three cups of leafy green vegetables daily, such as collards, turnip
greens, kale, broccoli, or bok choy (300 to 500 mg)
○ Add in one to two tablespoons of blackstrap molasses daily (135 to 270 mg)
○ Snack on figs (½ cup contains 120 mg calcium)

● Iron
○ Eat iron-rich plant foods
■ Chard, collard greens, spinach, pumpkin, squash, pine nuts, pistachios,
sunflower seeds, cashews, unhulled sesame seeds, white potatoes,
chocolate
○ Consume vitamin C-rich foods paired with non-heme iron-rich plant foods
■ Spinach & lemon juice, lentils & tomatoes, kale & sweet potato, for example
○ Consume one to two cups of legumes daily (especially lentils)
○ Add in one to two tablespoons of blackstrap molasses daily
○ Premenopausal women may need a supplement

● Omega-3 Fats (EPA/DHA)
○ Supplement with Vegan Omega-3s

● Vitamin A
○ Eat plenty of red, orange, yellow, and green plant foods
○ Do not supplement with beta-carotene

● Vitamin D
○ Get 30 minutes of sun exposure daily
○ Supplement in winter with 2,000 IU vitamin D3

● Zinc
○ Eat sesame seeds, pumpkin seeds, lentils, chickpeas, and cashews
○ Consider supplementing with 15 mg daily

Question 46

4 consequences of low HCl

Answer 46

1. Increased bacterial overgrowth in the small intestine, or SIBO
2. Impaired nutrient absorption
3. Decreased resistance to infection
4. Increased risk of cancer and other diseases

Problems in the stomach will often lead to problems further down the GI tract. For example,
secretion of pancreatic enzymes requires chyme from the stomach to be at a certain pH when it
enters the small intestine. If the stomach acid is low, the pH of the chyme will be too high, and the
pancreas won’t secrete digestive enzymes. This will lead to undigested food, especially
carbohydrates, which can lead to SIBO.

Question 47

RF for low HCl

Answer 47

PPIs or any acid-suppressing drugs, chronic stress, bacterial overgrowth, vegetarian diets (which
are low in protein and reduce acid production), H. pylori infection, genetic factors such as
polymorphisms and interleukin 1 that promote inflammation associated with hypochlorhydria, food
poisoning, and food intolerances. Another risk factor is pernicious anemia, which is an autoimmune
attack against the parietal cells in the stomach and/or an intrinsic factor, which is produced by the
parietal cells. These cells are also involved in acid production

Question 48

SIBO RF

Answer 48

Poor diet, low stomach acid, antibiotic use, acid-suppressing drugs, impaired function of the
migrating motor complex (MMC), constipation, gut infections, structural abnormalities of the GI
tract, and immune dysfunction.
SIBO is more likely in people with IBS, metabolic disorders, the elderly, celiac disease, chronic
constipation and diarrhea, long-term antibiotic use, and other organ dysfunction, particularly liver
disease and pancreatitis, both of which can alter the function of the MMC.

Question 49

5 things that influence gut microbiome

Answer 49

■ Diet proteins, fats, and especially carbohydrates and fiber, or fermentable carbohydrates
■ Medications, particularly antibiotics and NSAIDS
■ Chronic stress
■ Chronic infections
■ Physical inactivity

Question 50

3 major fxns of microbiome

Answer 50

1. Metabolic
   ■ Bacteria in the gut break down dietary compounds that might otherwise cause
   cancer; synthesize vitamins like biotin, folate, and vitamin K; convert non-digestible
   carbohydrates to short-chain fatty acids like butyrate, which play an important role;
   provide energy and benefit cells lining the gut; and help with the absorption of
   minerals like calcium, iron, and magnesium. Microbes also determine how we
   process and store the food we eat. We know that certain patterns of gut microbes
   increase energy storage and lead to obesity, whereas other patterns have the
   opposite effect and tend to lead to a lean phenotype.
2. Structural
   ■ Bacteria ferment carbohydrates to produce short-chain fatty acids like butyrate or
   propionate. Short-chain fatty acids then stimulate the growth and differentiation of
   epithelial cells. They also inhibit cell proliferation in the colon.
   ■ Dysbiosis can lead to the production of endotoxins like lipopolysaccharide (LPS),
   which activates zonulin, a protein that regulates intestinal permeability via its effect
   on the tight junctions. This LPS production can make the gut barrier more permeable.
3. Protective
   ■ The mucosal lining is the primary interface between the gut and the external
   environment. The gut contains the gut-associated lymphoid tissue (GALT), which
   comprises 70 to 80 percent of the immune cells in our body. The microbial
   composition of the gut has been shown to affect the composition and function of
   the GALT.

Question 51

antibody that looks at IBS-D

Answer 51

anti-CdtB (cytolethal distending protein B) and anti-vinculin (gut adhesion protein)

Question 52

anti-CdtB spec/sens

Answer 52

92, 44%

Question 53

anti-CdtB can also be high in what other condition

Answer 53

Celiac

Question 54

actomyosin antibodies

Answer 54

Antibodies can indicate transcellular permeability and movement of molecules through
cells.
• Very common in celiac.
• Antibodies to actomyosin alone indicate autoimmunity against the cell epithelium or other
tissues of the gut barrier.
• Any result above 10 is clinically significant, even if it’s marked as equivocal.