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Phone: 877-485-5336 Email: [email protected] Web: diagnosticsolutionslab.com RESEARCH. TECHNOLOGY. RESULTS.

INTERPRETIVE GUIDE GI-MAP ® – Unparalleled DNA Based Stool Testing Our mission: to deliver innovative, accurate and clinically relevant diagnostic testing in a timely and cost-effective manner FIRST OF ALL THANK YOU FOR CONSIDERING US!

“At Diagnostic Solutions Laboratory, we’re not content with the range of clinical testing currently available to practitioners. We believe that every patient should achieve optimal health, and we’re driven to give clinicians the tools to do so. Our mission, therefore, is to use our resources to bring the most advanced, innovative, and clinically relevant testing to healthcare providers worldwide.”

Tony Hoffman President and CEO

2 diagnosticsolutionslab.com GI-MAP® INTERPRETIVE GUIDE CONTENT

INTRODUCTION 4

HOW TO READ THE REPORT 5

PATHOGENS 6

H. pylori AND FACTORS 16

NORMAL/COMMENSAL 18

OPPORTUNISTIC BACTERIA 21

FUNGI/ 25

VIRUSES 27

PARASITES 29

INTESTINAL HEALTH MARKERS 34

ANTIBIOTIC RESISTANCE 38

REFERENCES 39

RESEARCH. TECHNOLOGY. RESULTS. 3 GI-MAP® INTRODUCTION

The Gastrointestinal Microbial Assay Plus (GI-MAP®) is an innovative clinical tool that measures gastrointestinal microbiota DNA from a single stool sample with state of the art, quantitative polymerase chain reaction (qPCR or real-time PCR) technology.

The GI-MAP was designed to detect microbes that may be disturbing normal microbial balance or contributing to illness as well as indicators of , absorption, , and immune function. The following guide may be useful for understanding the nature of each of the found on the GI-MAP, as well as clinical implications and treatment guidelines.

Please see the GI-MAP white paper for additional, fully referenced, information.

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HOW TO READ THE REPORT

GI-MAP quantifies bacteria, fungi, viruses, and parasites using qPCR. This is a leap forward from older methodologies that report only positive or negative. Results are reported as colony forming units per gram of stool (CFU/g). One CFU is roughly equivalent to one (or one cell). Results are expressed in standard scientific notation. A reported result of 3.5e7 is equivalent to 3.5 x 107 CFU/g, which equals 35,000,000 CFU/g, or 35 million CFU per gram of stool.

Figure 1. The normal reference range for C. difficile, A is 0–1,000 CFU/g. The patient’s result is very high at 1.21 x 105, or 121,000 CFU/g.

Reference ranges were developed using known positive, diseased samples to construct cut off values that distinguish disease-causing amounts of pathogenic and opportunistic microbes. Reference ranges for the were correlated with an FDA cleared assay for GI pathogens. The GI-MAP is capable of​ detecting as low as 0.1 cell per gram of stool.

Table 1. Scientific notation; a basic reference table.

1.0e1 1 X 101 10 Ten 1.0e2 1 X 102 100 One hundred 1.0e3 1 X 103 1,000 One thousand 1.0e4 1 X 104 10,000 Ten thousand 1.0e5 1 X 105 100,000 1.0e6 1 X 106 1,000,000

RESEARCH. TECHNOLOGY. RESULTS. 5 PATHOGENS

The GI-MAP includes pathogens (bacterial, parasitic, and viral) commonly known to intestinal . It’s important to note that not all individuals with positive findings for pathogens will present with symptoms. Many factors, including the health of the individual, the transient nature of some pathogens, and the presence and expression of virulence factors all contribute to an individual’s symptoms. are a type of produced by certain pathogens. Since GI-MAP is a DNA-based test, results reflect the levels of pathogenic strains carrying the toxin genes, not the levels of any toxins that may be produced.

Campylobacter » Vast majority of those with symptoms of gastroenteritis • Epidemiology recover without treatment » One of the most common causes • Therapeutic Approaches of in the U.S. & Considerations » Fecal contamination of » See patient’s calprotectin level poultry and to determine GI inflammation • Clinical Implications » Consider high dose , » May be infectious at very broad-spectrum antimicrobial herbs, low exposures and 5R Protocol (see Table 2) » Symptoms range from mild to » Heavy can be treated with severe , , azithromycin and fluoroquinolones fever, malaise; lasting several days to several weeks

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Clostridium difficile, » In asymptomatic patients with positive Toxin A and Toxin B toxins A and/or B, the genes are likely not “turned on,” and thus not causing The GI-MAP tests only for the genes for disease. It is still prudent to avoid toxin A and toxin B, which are carried by in these patients to prevent C. difficile. The GI-MAP does not measure CDAD. Consider antimicrobial herbal toxins directly for any microbe. formulas, which can suppress C. diff without activating toxin production. • Epidemiology » Additional testing for toxins A » 2–10% of population are carriers, and B may be warranted most are asymptomatic » Prolonged use of antibiotics may be causative factor Enterohemorrhagic E. coli (EHEC)

• Clinical Implications • Epidemiology » Symptoms include inflammation, » Fecal contamination of food abdominal pain, cramping, (undercooked beef, raw , and fever, and diarrhea unpasteurized juice) and water » Symptoms often present during » Implicated in hemorrhagic , use and often subside may progress to hemolytic once antibiotics are discontinued uremic syndrome (HUS) » Gastrointestinal (GI) • Clinical Implications can cause reactive arthritis » Symptoms include fever, • Therapeutic Approaches abdominal cramping, fatigue, & Considerations , and diarrhea » See patient’s calprotectin and » Symptoms may last up to a week secretory IgA (SIgA) levels to • Therapeutic Approaches determine GI inflammation & Considerations and immune response. » See patient’s calprotectin and SIgA » Consider Saccharomyces boulardii, levels to determine GI inflammation high dose probiotics, broad- and immune response. spectrum antimicrobial herbs, » Antibiotics may be contraindicated; and 5R Protocol (see Table 2) they can initiate hemolytic » Mild infections can be treated uremic syndrome (HUS) with » Consider high-dose probiotics (300+ » Heavy infections can be treated billion CFU/g) such as: with and fidaxomicin acidophilus‚ » Asymptomatic patients may bifidum‚ Bifidobacterium longum‚ not need treatment ‚

RESEARCH. TECHNOLOGY. RESULTS. 7 PATHOGENS

Table 2. Clinical Approach — The Five “R” Treatment Protocol. The 5R Protocol is a widely accepted clinical guideline to treating pathogens and imbalances in the GI microbiota and restoring health to the . Re-test patients with the GI-MAP in 3–6 months to monitor progress and make changes to the treatment protocol as needed.

Broad-spectrum antimicrobial herbs including: Antimicrobial berberine, caprylic , oil, oil of , uva ursi, olive leaf extract

Research the recommended antibiotic for the REMOVE specific microbe present. Avoid to Antibiotics which the microbe is thought to have resistance. Using a course of antimicrobial, Compare with GI-MAP findings for universal antiviral, , or antibiotic resistance genotype (an add-on test) antiparasitic therapies in cases where these are Antifungal Caprylic acid, garlic oil, oil of oregano, olive leaf extract present. It may also be necessary to remove offending foods, gluten, or that may be acting Black walnut, garlic oil, oil of oregano, Artemisia as antagonists. Antiparasitic (wormwood), berberine, goldenseal, gentian root extract, quassia bark extract, citrus seed extract

Olive leaf extract, purified silver, ’s claw, monolaurin, Antiviral osha root (Ligusticum porteri), vitamin A, vitamin C, vitamin D, reishi mushrooms, Echinacea, zinc

REPLACE In cases of maldigestion or Betaine hydrochloride, apple cider vinegar, Digestive , it may be herbal bitters, ox bile, , pancreatic support necessary to restore proper (, , ), pepsin digestion by supplementing with digestive enzymes.

REINOCULATE Lactobacillus acidophilus‚ Bifidobacterium bifidum‚ Bifidobacterium longum‚ Lactobacillus Probiotics Recolonization with rhamnosus‚ Bifidobacterium breve‚ Lactobacillus healthy, beneficial bacteria. casei‚ Saccharomyces boulardii Supplementation with probiotics, along with the use of prebiotics Beta-glucan, fiber, , pectin, xylooligosaccharides, helps re-establish the proper Prebiotics galactooligosaccharides, larch microbial balance.

Immune Colostrum, immunoglobulins, S. boulardii REPAIR Support

Restore the integrity of the gut L-Glutamine, aloe vera extract, deglycyrrhizinated mucosa by giving support to Intestinal licorice, marshmallow root, okra, N-acetyl glucosamine, healthy mucosal cells, as well as Barrier Repair quercetin, S. boulardii, slippery elm, zinc carnosine, immune support. vitamin A, essential fatty , B vitamins

REBALANCE Support Address whole body health and Sleep, diet, exercise, and management Consideration lifestyle factors so as to prevent future GI dysfunction.

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Bifidobacterium breve‚ Lactobacillus • Clinical Implications casei‚ thermophilus » Symptoms may include severe » Consider bacteriophages, broad- abdominal cramps and diarrhea spectrum antimicrobial herbs, » Shiga toxins inhibit protein synthesis and 5R Protocol (see Table 2) & elicit strong inflammatory response

• Therapeutic Approaches E. coli O157 & Considerations • Epidemiology » See patient’s calprotectin and SIgA » Fecal contamination of food levels to determine GI inflammation and liquids (dairy, undercooked and immune response. beef, vegetables, juices) » Antibiotics may be contraindicated; » Implicated in many outbreaks and they can initiate HUS cases of bloody diarrhea and HUS » Consider high-dose probiotics » High prevalence worldwide (300+ billion CFU/d) » Consider bacteriophages, broad- spectrum antimicrobial herbs, and 5R Protocol (see Table 2)

SOURCES OF EXPOSURE AND RE-INFECTION

To effectively treat infections and prevent reinfection, exposure should be identified and eliminated. Most exposure to pathogens occurs via fecal- oral transmission, most often due to use of contaminated water sources or improper hand hygiene. This may include drinking contaminated water, eating raw foods washed in contaminated water or harvested (e.g. shellfish) in contaminated water, or improper handwashing.

To remove microorganisms from food, the FDA recommends first washing your hands, running cool water over fruits and vegetables, while rubbing or scrubbing, and then letting them dry out before eating. During treatment, consider all possible sources of fecal transmission: romantic partners, children (especially if in diapers or not toilet-trained), sheets, towels, water source to the home, etc...

RESEARCH. TECHNOLOGY. RESULTS. 9 PATHOGENS

Enteroinvasive E. coli • Therapeutic Approaches (EIEC)/ & Considerations » See patient’s calprotectin and SIgA • Epidemiology levels to determine GI inflammation » Fecal contamination of ingested foods and immune response • Clinical Implications » Antibiotics may be contraindicated; » Symptoms include diarrhea (with blood they can initiate HUS and/or mucus), , fever, chills, » Consider high-dose probiotics fatigue, and abdominal cramping (300+ billion CFU/d) » Symptoms are generally self-limiting » Consider bacteriophages, broad- » Gastrointestinal (GI) infection spectrum antimicrobial herbs, can cause reactive arthritis and 5R Protocol (see Table 2)

• Therapeutic Approaches & Considerations Enterotoxigenic E. coli » See patient’s calprotectin and SIgA levels to determine GI inflammation • Epidemiology and immune response. » Most common cause of » Antibiotics may be contraindicated; traveler’s diarrhea they can initiate HUS • Clinical Implications » Consider high-dose probiotics » Diarrhea is the most (300+ billion CFU/d) common symptom » Consider bacteriophages, broad- • Therapeutic Approaches spectrum antimicrobial herbs, and & Considerations 5R Protocol (see Table 2) » See patient’s calprotectin and SIgA levels to determine GI inflammation Enteropathogenic E. coli (EPEC) and immune response • Epidemiology » Antibiotics may be contraindicated; » Fecal contamination of ingested they can initiate HUS foods (hamburger meat, unpasteurized » Consider high-dose probiotics milk, and contaminated water) (300+ billion CFU/d) • Clinical Implications » Consider bacteriophages, broad- » Symptoms include watery, spectrum antimicrobial herbs, bloody diarrhea and 5R Protocol (see Table 2)

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Shiga-like Toxin E. coli (STEC) » Symptoms include fever, vomiting, and severe diarrhea • Epidemiology » Typically self limiting within seven days » Fecal contamination of ingested foods (undercooked meat, » GI infection can cause reactive unpasteurized milk, juice, and water) arthritis and may be involved in ankylosing spondylitis • Clinical Implications » Systemic infections may require » Symptoms may include severe treatment with antibiotics abdominal cramps and diarrhea • Therapeutic Approaches » Toxins may elicit strong & Considerations inflammatory response » See patient’s calprotectin and SIgA • Therapeutic Approaches levels to determine GI inflammation & Considerations and immune response » See patient’s calprotectin and SIgA » Remove sources of infection levels to determine GI inflammation » Consider high-dose probiotics and immune response (300+ billion CFU/d) » Antibiotics may be contraindicated; » Consider broad-spectrum they can initiate HUS antimicrobial herbs and 5R » Consider high-dose probiotics Protocol (see Table 2) Antibiotics (300+ billion CFU/d) are contraindicated; they may » Consider bacteriophages, broad- cause relapse of infection spectrum antimicrobial herbs, and 5R Protocol (see Table 2) » Antibiotics and antidiarrheal medicines Table 3. Food Sources of . are contraindicated; they may

increase the risk of developing HUS Poultry Salmonella Poultry Products • Epidemiology Meat » Fecal contamination of ingested foods Dairy (eggs, poultry, meat, unpasteurized Raw, Fresh, Ready-to-eat Produce such as: milk, raw fruits, and vegetables) • Tomatoes • Leafy greens » Exposure to pets (reptiles, • Sprouts • Berries • Melons amphibians, baby chicks)

• Clinical Implications » May be asymptomatic

RESEARCH. TECHNOLOGY. RESULTS. 11 PATHOGENS

Vibrio cholerae • Epidemiology • Epidemiology » Fecal contamination of ingested » Fecal contamination of ingested foods (raw shellfish) and often picked foods and liquids (water, undercooked up during international travel pork, meats, and dairy products)

• Clinical Implications • Clinical Implications » May be asymptomatic or » Symptoms usually develop four cause mild symptoms to seven days after exposure » Severe infections present with and are self-limiting profuse watery diarrhea (“rice-water » Symptoms include water stools”), vomiting, rapid heart rate, or bloody diarrhea, fever, loss of elasticity, thirst, dry vomiting, and abdominal pain mucous membranes, low blood (may resemble ) pressure, restlessness, or irritability » Symptoms may mimic Crohn’s disease • Therapeutic Approaches » May trigger autoimmune thyroiditis & Considerations or inflammatory arthritis in » See patient’s calprotectin and SIgA susceptible individuals levels to determine GI inflammation • Therapeutic Approaches and immune response. & Considerations » Rehydration therapy » Consider probiotics, broad- » Zinc, especially in children spectrum antimicrobial herbs » Consider probiotics, broad- and 5R Protocol (see Table 2) spectrum antimicrobial herbs » Heavy infections can be treated and 5R Protocol (see Table 2) with doxycycline in combination » Heavy infections may be treated with an with doxycycline; refer to GI-MAP » Trimethoprim-sulfamethoxasole, findings for universal antibiotic chloramphenicol, and resistance genotype, if possible may also be useful treatments » Refer to GI-MAP findings for universal antibiotic resistance genotype, if possible

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PARASITIC PATHOGENS

Cryptosporidium Entamoeba histolytica

Epidemiology • Epidemiology » Fecal contamination of ingested » Fecal contamination of foods and liquids (contaminated ingested foods or water water and swimming pools, » Pets may be a source of exposure undercooked meat, and raw milk) » Sexual contact may be a » Common cause of traveler’s diarrhea source of exposure

• Clinical Implications • Clinical Implications » Symptoms typically last 2–3­ » Symptoms include diarrhea, weeks and are self-limiting fulminating colitis (resembling » If symptoms persist, look for sources of ), and contamination, such as drinking water » Extreme cases may invade » Can cause reactive arthritis and tissues

• Therapeutic Approaches • Therapeutic Approaches & Considerations & Considerations » May not require treatment » See patient’s calprotectin and SIgA levels to determine GI inflammation » See patient’s calprotectin and SIgA and immune response levels to determine GI inflammation and immune response » Treatment may be indicated, even in asymptomatic carriers » If necessary, consider anti-parasitic herbal treatments containing » Mild infections can be treated ingredients such as black walnut, with Iodoquinol, paromomycin, * garlic oil, oil of oregano, Artemisia or diloxanide furoate (wormwood), berberine, goldenseal, » Moderate to heavy infections can gentian root extract, quassia bark be treated with metronidazole extract, citrus seed extract or tinidazole, followed by * » Consider probiotics and iodoquinol or paromomycin 5R Protocol (see Table 2) » If appropriate, consider anti-parasitic » Search for and remove sources herbal treatments (see Table 2) of fecal contamination » Consider probiotics and » Heavy infections can be 5R Protocol (see Table 2) treated with nitazoxanide* » Avoid reinfection by fecal contamination

RESEARCH. TECHNOLOGY. RESULTS. 13 PATHOGENS

Giardia » May cause malnutrition and deficiency • Epidemiology » Can cause reactive arthritis » Most commonly isolated protozoan worldwide • Therapeutic Approaches » Found in outside water sources & Considerations (lakes, streams, ponds) and can » See patient’s calprotectin and SIgA get past filtration systems levels to determine GI inflammation » Carried by and immune response » Common in daycare workers » Infections can be treated with tinidazole, nitazoxanide, • Clinical Conditions metronidazole, paramomycin, » May be asymptomatic, especially furazolidone, or quinacrine* in patients with adequate levels » Consider probiotics and 5R of normal bacteria and SIgA Protocol (see Table 2) to repair » Symptoms include diarrhea, and rebuild the gut mucosa , cramps, , intestinal malabsorption, and * Additional information (dosing, efficacy, etc.) on » Can cause urticaria or neurologic pharmaceutical treatment for parasites may be symptoms such as irritability, found at www.cdc.gov/parasites/index.html and in sleep disorder, or depression the Physician’s Desk Reference.

Giardia intestinalis protozoan

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VIRAL PATHOGENS

Adenovirus 40/41 Norovirus GI/GII • Epidemiology • Epidemiology » Common cause of diarrhea in infants » Fecal contamination of and children but can also affect adults ingested foods and water » Mainly transmitted by fecal » Common cause of contamination (fecal-oral route) flu on cruise ships

• Clinical Implications » Common cause of non- bacterial gastroenteritis and » Causative agents of gastrointestinal outbreaks in the world disease and gastroenteritis » Symptoms include fever and watery • Clinical Implications diarrhea, usually limited to 1–2 weeks » Symptoms include nausea and » May also be present in the stool vomiting, diarrhea, abdominal of asymptomatic carriers and cramps, low-grade fever, muscle may not require treatment aches, fatigue, and headache » Generally short-lived, lasting • Treatment about 24–72 hours » Handwashing » Hydration • Treatment » Antiviral herbs such as cat’s claw, » Antivirals are not recommended osha root, reishi mushrooms, » Supportive care for the gastric vitamins A, C, and D, zinc, Echinacea mucosa, hydration, and immune- » Address other imbalances on boosting agents may be warranted the GI-MAP and use 5R Protocol – Handwashing (see Table 2) to rebuild gut – Hydration health and gut immunity – Antiviral herbs such as cat’s claw, osha root, reishi mushrooms, vitamins A, C, and D, zinc, Echinacea – Address other imbalances on the GI-MAP and use 5R Protocol (see Table 2) to rebuild gut health

RESEARCH. TECHNOLOGY. RESULTS. 15 H. pylori AND VIRULENCE FACTORS

Helicobacter pylori (H. pylori) • Epidemiology » Fecal contamination, oral to oral, Recent studies have shown that nearly and family inter-infection are 50% of the world’s population may harbor common modes of transmission H. pylori. And, although many carriers are asymptomatic, H. pylori is known to • Clinical Implications have a causative role in , chronic » Dyspepsia, abdominal pain, , and . Additionally, nausea, vomiting and chronic in early phases of colonization, patients gastrointestinal symptoms may experience hypochlorhydria followed » ulcers by a change to hyper aciduria. Over time, » May induce mucosal atrophy additional H. pylori strains may colonize, and metaplastic changes including those with Virulence Factors and increased disease potential.

Table 4. H. pylori virulence factors and disease associations. For more details, refer to the GI-MAP white paper.

Gene Acronym Name Association with Disease Induces inflammation, promotes BabA Blood Group binding adhesin long-term infection CagA Cytotoxin-Associated Protein A Gastric cancer and peptic Cag PAI Cag Pathogenicity Island, includes virB and virD Gastric cancer and peptic ulcer Promotes inflammation; associated DupA Duodenal Ulcer-Promoting gene A with increased duodenal ulcers Gastric inflammation, peptic ulcer IceA Induced by Contact with Epithelium A disease, and gastric cancer

OipA Outer Inflammatory Protein A Gastric cancer and peptic ulcer

Damages mitochondria, associated VacA Vacuolating Toxin A with gastric inflammation, , and gastric cancer

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Virulence Factors » Consider high-dose probiotics and 5R Protocol (see Table 2) Of the 50% of the population believed to » Rebuild healthy be infected with H. pylori, only 2% develop by reducing stress and giving gastric cancer. Positive H. pylori virulence soothing and healing agents such as factors on the GI-MAP represent the genetic glutamine, aloe, DGL, and vitamin A potential for an H. pylori strain to cause » Address dental hygiene; the pathology. For example, some clinicians mouth is a reservoir for H. pylori may choose an aggressive treatment protocol for a patient with dyspepsia and » Consider sources of exposure, a family history of gastrointestinal cancer, especially romantic partners who shows elevated H. pylori and positive or family members virulence factors. (See Table 4) » Address other imbalances on the GI-MAP • Treatment » For peptic ulcer disease, the first- » Asymptomatic patients may line triple therapy (prescription) not require treatment treatment includes a proton pump » Consider herbal formulas to eradicate inhibitor, , and or suppress H. pylori. Ingredients may or metronidazole include: deglycyrrhizinated licorice, » Fluoroquinolones and mastic gum, methylmethionine are used in second-line sulfonium chloride, vitamin C, regimens against H. pylori1 zinc carnosine, citrate, » See the GI-MAP Antibiotic Resistance berberine, goldenseal, oil of oregano, Genes results for when grape extract, Chinese goldthread designing an antibiotic protocol extract, yerba mansa extract

» See pancreatic elastase-1 to Note: In supporting individuals with H. pylori, consider determine if maldigestion and/or the patient history, clinical symptoms, virulence genes, and the amount of H.pylori DNA detected in order to hypochlorhydria might be present design a customized treatment plan.

Figure 2. An example antibiotic resistance gene measured on the GI-MAP for H. pylori. Number and letter combinations are single nucleotide polymorphisms (SNPs), or gene targets, that are involved in H. pylori . If any SNP is detected (present), then the H. pylori strain/s are resistant to that class of antibiotics. In this example, the patient’s H. pylori is resistant to the clarithromycin class of antibiotics and it would be prudent to use a different antibiotic when tailoring a treatment protocol.

RESEARCH. TECHNOLOGY. RESULTS. 17 NORMAL/ COMMENSAL BACTERIA

Trillions of microorganisms inhabit the intestine to make up a complex ecosystem that plays an important role in human health. Commensal bacteria extract nutrients and energy from our diets, maintain gut barrier function, produce vitamins (biotin and vitamin K), and protect against colonization by potential pathogens.

Bacteria Lactobacillus, which are part of normal flora of human intestine

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THE FOLLOWING NORMAL/COMMENSAL BACTERIA ARE REPORTED ON THE GI-MAP

Keystone and primary mucus degrader. Generates mucus-derived Akkermansia and metabolic products that support the growth and energy needs of other gut municiphila microbes. Promotes mucosal health and mucus production. Low levels associated with and metabolic dysfunction. High levels linked to multiple sclerosis.

Gram-negative species of the . Immune-modulating normal gut species. Believed to be involved in microbial balance, barrier integrity, and fragilis neuroimmune health (Hsiao 2013). High levels may result from reduced digestive capacity or . Low levels may contribute to reduced anti-inflammatory activity in the intestine.

Gram-positive in the phylum. Present in breast milk. Colonizes the human GI tract at birth. Common in probiotics. Thrives on a wide variety of Bifidobacterium spp. fibers. Low levels may result from low fiber intake or reduced mucosal health. High levels are more common in children than in adults.

Prominent and diverse group of bacteria in the microbiome of the . Important producers of short-chain fatty acids, including butyrate. Promote a (class) healthy mucosal barrier, influence immune balance, and protect against many gastrointestinal pathogens. Low levels often associated with inflammatory and autoimmune conditions. High levels may be associated with metabolic dysfunction.

Gram-positive genus of lactate-producing bacteria in the phylum. High spp. levels may be due to reduced digestive capacity, constipation or small intestinal bacterial overgrowth. Low levels may indicate insufficiency of beneficial bacteria.

Gram-negative genus in the phylum. Normal gut flora. (E. coli) is the primary species in this genus. Most E. coli are nonpathogenic (pathogenic E. coli strains are measured separately in “Pathogens” section of the GI-MAP). Escherichia spp. High levels may be indicative of increased intestinal inflammatory activity. Low levels may indicate reduced mucosal health and decreased protection against pathogenic E. coli.

Widely recognized as an important keystone species in the Clostridia class, as well as a major butyrate producer. Promotes anti-inflammatory processes and mucosal prausnitzii homeostasis. Reduced levels have been associated with a wide range of chronic inflammatory and autoimmune diseases.

Gram-positive genus of lactate-producing bacteria in the Firmicutes phylum. Many strains used as probiotics. High levels may result from reduced digestive capacity Lactobacillus spp. or excessive intake of . Low levels may be due to low intake or high salt intake, and may also indicate reduced mucosal health.

Gram-negative genus in the Proteobacteria phylum. Closely related to E. coli (in the Enterobacter spp. same taxonomic family). High levels may indicate increased intestinal inflammatory activity. Low levels may indicate reduced mucosal health.

RESEARCH. TECHNOLOGY. RESULTS. 19 NORMAL/COMMENSAL BACTERIA

• Therapeutic Options for Abnormally Low Commensal Bacterial Findings FIRMICUTES AND » Use a broad-spectrum, diverse BACTEROIDETES PHYLA formula, 50–450 billion Gram-negative Bacteroidetes and gram- CFUs/day depending on findings. positive Firmicutes are that May contain: Lactobacillus acidophilus‚ dominate the entire human digestive tract, Bifidobacterium bifidum‚ Bifidobacterium including the mouth, nose, throat, and longum‚ Lactobacillus rhamnosus‚ colon.2 An abnormal result in one or both of Bifidobacterium breve‚ Lactobacillus these phylum suggest imbalanced normal casei‚ Streptococcus thermophilus. microbes in the GI tract. Further, high » Increase dietary intake of vegetables Firmicutes and low Bacteroidetes (resulting in and fibers(, bran) a high F/B ratio) suggest microbial imbalance » Remove dietary and which may be related to increased caloric refined carbohydrates extraction from food, fat deposition and » Prebiotic supplementation (resistant lipogenesis, impaired insulin sensitivity, and starch, xylooligosaccharide, inulin, increased inflammation. beta-glucan, ) » Fermented foods, if tolerated High Firmicutes/Bacteroidetes Ratio » Reduce inflammation and address other imbalances on the GI-MAP • Causes: » Poor diet • Therapeutic Options for Abnormally High Commensal Bacterial Findings » Dysbiosis » Consider any additional findings » Maldigestion or hypochlorhydria on GI-MAP and treat accordingly • Therapeutic Approaches » Re-establish commensal bacteria & Considerations using 5R protocol (see Table 2) » Balance commensal bacteria using » Remove dietary sugar and the 5R Protocol (see Table 2) refined carbohydrates » When Firmicutes phyla is high, consider » In certain situations, overgrowth of using Bifidobacteria probiotics and commensal bacteria may be treated Saccharomyces boulardii primarily. judiciously with antimicrobial herbs » Lactobacillus spp. when all other findings are normal. and spp. (found in probiotics) can elevate Firmicutes » Optimize the diet; a lower fat diet may help to normalize the F/B ratio » Address all other imbalances on the GI-MAP

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OPPORTUNISTIC BACTERIA

Many bacteria measured on the GI-MAP are considered opportunistic pathogens, as they only cause disease and illness in some individuals, particularly the immune-compromised. Many individuals come into contact with opportunistic bacteria and experience no symptoms. Most sources consider these microbes to be normal in the stool. However, they can cause gastroenteritis and inflammation at high levels in vulnerable patients. Symptoms may include diarrhea, loose stools, abdominal pain, or even constipation. Overgrowth and excessive colonization by opportunistic bacteria may occur when the commensal bacteria are impaired by poor diet, antibiotic use, parasitic infection, or a weakened immune system. When intestinal permeability is present (see zonulin), these microbes could escape the lumen of the gut and infect extraintestinal sites.

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OPPORTUNISTIC BACTERIA REPORTED AS DYSBIOTIC/OVERGROWTH

Common group of gram-positive bacteria in the Firmicutes phylum. Some strains are Bacillus spp. used as probiotics. High levels may result from reduced digestive function, SIBO, or constipation.

Gram-positive species in the Firmicutes phylum. High levels may result from reduced stomach acid, PPI use, compromised digestive function, SIBO or constipation. High natural resistance to some antibiotics, which may result in overgrowth.

Family of bacteria-like microbes that produce . Facilitates carbohydrate and short-chain fatty acid production by beneficial bacteria. High levels Methanobacteriaceae linked to chronic constipation, as well as some types of SIBO and IBS. Low levels may (family) indicate reduced production of short-chain fatty acids and may be associated with inflammation.

Gram-negative group in the Proteobacteria phylum. May produce . High levels Morganella spp. may indicate increased intestinal inflammatory activity. High levels may cause diarrhea, and may also be associated with SIBO.

Pseudomonas spp. Gram-negative bacteria in the Proteobacteria phylum. High levels may indicate increased intestinal inflammatory activity and may cause abdominal cramping and loose stools. aeroginosa Some strains of P. aeroginosa may produce toxins that can damage cells.

Gram-positive bacteria in the Firmicutes phylum. High levels may result from reduced spp. digestive capacity, and intestinal inflammatory activity. Some strains may produce toxins and contribute to loose stools or diarrhea.

Gram-positive bacteria in the Firmicutes phylum. Streptococcus spp. colonize skin and mucous membranes throughout the body; High levels in the intestine may result from Streptococcus spp. low stomach acid, PPI use, reduced digestive capacity, SIBO or constipation; Elevated levels may also be indicative of intestinal inflammatory activity, and may cause loose stools.

Citrobacter spp. Gram-negative bacteria in the Proteobacteria phylum. High levels may indicate increased intestinal inflammatory activity.

Genus of gram-negative bacteria in the phylum. Commonly found in the Fusobacterium spp. oral cavity, and may also be found in the intestine. Associated with inflammatory processes, as well as autoimmune conditions such as systemic sclerosis.

Gram-negative bacteria in the Proteobacteria phylum. Common residents of the oral Klebsiella spp. cavity and respiratory tract. May cause diarrhea, , abdominal pain, and bloating; Common after long-term antibiotic use; May release histamine in the gut; High levels may indicate increased intestinal inflammatory activity.

Mycobacterium avium Bacterial species in the Actinobacteria phylum. Higher levels have been associated with subsp. paratuberculosis Crohn’s disease and rheumatoid arthritis.

Gram-negative species in the Bacteroidetes phylum. Associated with rheumatoid copri arthritis. High levels may result from reduced digestive capacity, or a high-starch diet.

Gram-negative bacteria in the Proteobacteria phylum. High levels may indicate increased Proteus spp. intestinal inflammatory activity; May contribute to loose stools or diarrhea; Pets or wild animals can be a source

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Bacillus cereus

• Therapeutic Options and » Address all other imbalances Considerations for Abnormally High on the GI-MAP Levels of Opportunistic Bacteria » Refer to Universal Antibiotic » Consider high-dose probiotics Resistance findings onGI-MAP (300+ billion CFU/d) to design a pharmaceutical » Consider broad-spectrum treatment plan, if necessary antimicrobial herbs including: » If using antibiotics, see the berberine, caprylic acid, garlic oil, oil of Physician’s Desk Reference for oregano, uva ursi, or olive leaf extract appropriate antibiotics for the specific » Optimize diet (low sugar, low refined microorganisms that are overgrown carbs, high -based foods and fiber) » If using antibiotics, consider rifaxamin, » See SIgA level to determine mucosal which remains in the GI tract and immunity and if patient is protected is also used to treat small intestinal from overgrowth symptoms bacterial overgrowth (SIBO) » Use the 5R Protocol (see Table 2) » Identify and remove potential sources of contamination or re-infection

RESEARCH. TECHNOLOGY. RESULTS. 23 OPPORTUNISTIC BACTERIA

• Opportunistic Bacteria as a or sustain the autoimmune process. Trigger for Autoimmunity Gastrointestinal symptoms are less » Certain opportunistic bacteria may common when these bacteria are initiate autoimmune thyroiditis elevated. When intestinal permeability or inflammatory arthritis such as is present (see zonulin), these microbes rheumatoid arthritis and ankylosing could escape the lumen of the gut spondylitis. These bacteria may trigger and infect extraintestinal sites.

Table 5. Opportunistic Bacteria and Viruses Associated with Autoimmunity.

Opportunistic Autoimmune Association Bacteria Citrobacter spp. Rheumatoid arthritis

Fusobacterium spp. Systemic sclerosis or inflammatory bowel disease

Crohn’s disease, ulcerative colitis, ankylosing spondylitis, and other Klebsiella spp. spondyloarthropathies (which include ankylosing spondylitis, arthritis associated with Crohn’s or ulcerative colitis, psoriatic arthritis, and reactive arthritis)

M. avium subsp. Rheumatoid arthritis, Crohn’s disease, Type I , possibly psoriasis paratuberculosis

Prevotella copri Rheumatoid arthritis

Proteus spp. Rheumatoid arthritis

Proteus mirabilis Rheumatoid arthritis and spondyloarthropathies (listed above)

Viruses Autoimmune Association

Systemic lupus erythematosus, systemic sclerosis, type 1 diabetes, CMV rheumatoid arthritis

Rheumatoid arthritis, lupus, Sjogren’s, multiple sclerosis, autoimmune EBV thyroid disorders

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FUNGI/YEAST

Fungal organisms are commonly found in the human digestive tract, but fungal overgrowth can cause illness in susceptible individuals. Fungal growth may be localized in the body. For instance, Candida spp. may be high in the large intestine but normal in the , and vice versa. In a patient with suspected fungal overgrowth, additional tests may be necessary to understand the complete picture of fungal overgrowth. Urinary D-arabinitol or to Candida are sometimes used.

• Common Causes of Yeast infections. May cause diarrhea. Overgrowth Include: Has been suggested to cause a » Antibiotic use cluster of symptoms including GI » High intake of sugar, starches, complaints, fatigue, and muscle or and dietary fungi (, joint pain but evidence is weak. , nuts, cheese, corn) » Geotrichum spp. » Hypochlorhydria – May cause disease in » Impaired immune function immunosuppressed patients. » Dysbiosis Low levels may be a dietary artefact; certain strains are • Fungi/Yeast Targeted on the GI-MAP used to make soft cheeses. » Candida albicans and Candida spp. » Microsporidia spp. – Commensal fungi that – The GI-MAP specifically detects can be pathogenic to Encephalitozoon intestinalis, which immunocompromised patients. affects the GI. May cause diarrhea Causes vaginal yeast infections and wasting. Can disseminate and can be fatal in systemic

RESEARCH. TECHNOLOGY. RESULTS. 25 FUNGI/YEAST

Candida albicans

to ocular, genitourinary, • Therapeutic Options and and respiratory tracts. Considerations for Abnormally High Levels of Fungi/Yeast » Rhodotorula spp. » Reduce intake of sugars, – Common in soil, , starches, and fungi bathrooms, and in beverages like » See SIgA levels and consider milk, juice, and water. May be a immune support commensal. Can cause disease in immunosuppressed patients. » Consider high-dose probiotics, Saccharomyces boulardii, and • Common Symptoms of the 5R Protocol (see Table 2) Fungal Dysbiosis » Consider antifungal herbs such » GI symptoms: Gas, bloating, as caprylic acid, undecylenic acid, constipation, nausea, oregano oil, berberine, and/or garlic vomiting, and diarrhea. » Consider pharmaceutical » Other symptoms: Eczema, in severe cases. Nystatin is preferred athlete’s foot, vaginal yeast because it stays in the GI tract. infections, thrush, and jock itch.

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VIRUSES

Cytomegalovirus • Epidemiology » Herpes virus that has infected 60% of the US population » One in three children have contracted CMV by five years old » Passed around in child daycare centers

• Clinical Implications » Positive CMV on the GI-MAP indicates active infection of is a viral genus of the viral family the GI, NOT past infection known as Herpesviridae » Active infection may be asymptomatic or cause mild flu-like symptoms • Therapeutic Options and » CMV can also cause viral , Considerations transaminitis, , » No treatment is needed colitis, fever, and encephalitis if asymptomatic » Common in inflammatory bowel » Prevent spreading CMV with disease, immunocompromised regular handwashing patients » Antiviral herbs such as cat’s claw, » CMV colitis has a similar presentation osha root, reishi mushrooms, to difficile infection vitamins A, C, and D, zinc, Echinacea » CMV has been implicated in » Address other imbalances on autoimmune diseases: lupus, the GI-MAP and use 5R Protocol systemic sclerosis, type 1 diabetes, (see Table 2) to rebuild gut and rheumatoid arthritis health and gut immunity

RESEARCH. TECHNOLOGY. RESULTS. 27 VIRUSES

Epstein Barr Virus arthritis, lupus, Sjogren’s, multiple sclerosis, autoimmune • Epidemiology thyroid disorders » One of the most common » EBV may increase the risk of gastric viruses worldwide; infects cancer; especially if H. pylori present 90–95% of the population » May cause colitis » Commonly contracted in childhood and causes mild symptoms » Found in 30–64% of IBD patients

• Clinical Implications • Therapeutic Options and Considerations » Positive finding on theGI-MAP » Rest and hydration indicates active EBV infection of the GI, not past infections » Antiviral herbs such as cat’s claw, osha root; antiviral fungi such as » Can cause infectious reishi and/or Cordyceps mushrooms mononucleosis (mono) » Vitamins A, C, and D, zinc, Echinacea » Symptoms include fatigue, fever, swollen lymph nodes, inflamed » Address other imbalances on throat, enlarged spleen, and more the GI-MAP and use 5R Protocol (see Table 2) to rebuild gut » May last two to four weeks in health and gut immunity adolescents and adults » Follow-up blood testing may be » May cause fatigue for weeks or months indicated, including an EBV Early » Associated with autoimmune Antigen and EBV PCR test conditions such as rheumatoid

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PARASITES

A parasite is an that and feeds on a organism at the expense of the host. The GI-MAP tests for pathogenic parasites and protozoa (some of which are non-pathogenic) most commonly occurring in the GI tract. Sources of exposure should be identified and eliminated to prevent reinfection.

PROTOZOA

Blastocystis hominis » Consider nitazoxanide or tinidazole, oregano oil, and S. boulardii • Epidemiology » Herbal treatments may » Fecal contamination of food not be as effective or water is common » Consider Artemisia, Coptis, or » Found worldwide other broad-spectrum anti- • Clinical Implications parasitic herbal formulas » Symptoms include diarrhea, » Infection can be treated with abdominal pain, nausea and metronidazole, iodoquinol or vomiting, fever, fatigue, irritable trimethoprim/sulfamethoxazole* bowel syndrome, infective arthritis » Consider probiotics and 5R Protocol (see Table 2) • Therapeutic options and considerations » Difficult to eradicate

RESEARCH. TECHNOLOGY. RESULTS. 29 PARASITES

Chilomastix mesnili • Epidemiology » Fecal contamination of food or water

• Clinical Implications » Considered non-pathogenic and may not cause symptoms » May indicate dysbiosis or suppressed immunity Cyclospora

• Therapeutic Options » Can cause bloating, and Considerations , and » Look for and address sources » of fecal-oral contamination Flu-like symptoms such as fatigue, headaches, and low fever may be » Consider probiotics and present in some individuals 5R Protocol (see Table 2) » Infection is usually self-limiting, with » Address other imbalances symptoms usually lasting about seven on the GI-MAP days, but can last weeks or months in immunosuppressed patients Cyclospora spp. • Therapeutic Options () and Considerations » In cases lasting more than seven • Epidemiology days, treatment with an antibiotic » Fecal contamination of food and water combination of trimethoprim and » Associated with water- and sulfamethoxazole may be necessary* food-borne outbreaks » Consider probiotics, broad-spectrum » Common cause of traveller’s diarrhea anti-parasitic herbal formula, and » May be found on imported fresh the 5R Protocol (see Table 2) produce from tropical regions » Look for and address • Clinical Implications sources of reinfection » Symptoms include prolonged watery diarrhea, abdominal cramping, loss of appetite, weight Dientamoeba fragilis loss, nausea, and vomiting • Epidemiology » May cause alternating » Not well understood; probably fecal diarrhea and constipation contamination of food or water

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• Clinical Implications » Look for and address sources » May be asymptomatic of fecal contamination » May cause diarrhea, abdominal » Address other imbalances pain, nausea, fever, fatigue, weight on the GI-MAP loss, appetite loss, and/or fatigue • Therapeutic Options Entameoba coli and Considerations • Epidemiology » “Moderate” amounts of DNA, that are not above the laboratory » Fecal contamination of food or water reference range, may cause » Found in the large intestine, symptoms and warrant treatment considered to be non-pathogenic » Infection can be treated with • Clinical Implications iodoquinol, paromomycin, » May be indicative of dysbiosis, * or metronidazole conservative treatment may be » Consider probiotics, broad-spectrum indicated if clinical presentation is anti-parasitic herbal formula, and consistent with enteroparasitosis the 5R Protocol (see Table 2) • Therapeutic Options » Look for and address and Considerations sources of reinfection » Consider probiotics and the » Address other imbalances 5R Protocol (see Table 2) on the GI-MAP » Look for and address sources of fecal contamination Endolimax nana » Address other imbalances on the GI-MAP • Epidemiology » Fecal contamination of food or water

• Clinical Implications Pentatrichomonas hominis » Considered non-pathogenic; • Epidemiology individuals may be asymptomatic » Fecal contamination of food or water

» May be indicative of dysbiosis, • Clinical Implications conservative treatment may be » Considered harmless, a non- indicated if clinical presentation is » Infected individuals are consistent with enteroparasitosis usually asymptomatic • Therapeutic Options » May contribute to dysbiosis and Considerations » Also colonizes , , » Consider probiotics and the and other animals 5R Protocol (see Table 2) RESEARCH. TECHNOLOGY. RESULTS. 31 PARASITES

• Therapeutic Options • Clinical Implications and Considerations » Early symptoms are itching and rash » May be asymptomatic where the larvae penetrated the skin » In women with vaginosis, consider » Symptoms of heavy infestations treatment to reduce chances include: abdominal pain, of vaginal contamination or diarrhea, fatigue, weight loss, reinfection (find treatments for (IDA), Trichomonas vaginalis elsewhere) coughing, and loss of appetite » If treatment is needed, consider » Infected individuals may a broad-spectrum anti- also be asymptomatic parasitic herbal formula • Therapeutic Options » Consider probiotics and the and Considerations 5R Protocol (see Table 2) » Heavy infections can be treated with » Look for and address sources albendazole or mebendazole* of fecal contamination » Individuals presenting with IDA » Address other imbalances may need iron supplementation on the GI-MAP » Consider anti-parasitic herbal treatments, gut immunity support, and the 5R Protocol (see Table 2) WORMS » Look for and remove sources of reinfection

Ancylostoma duodenale and Necatur americanus (Hookworms) Ascaris lumbricoides (Roundworm) • Epidemiology • Epidemiology » Infection occurs via skin contact » Fecal contamination of food or water with soil contaminated with » Common in international larvae or ingestion of larvae travellers and recent immigrants » Infected cats and dogs are from Latin America and Asia a source of exposure • Clinical Implications » Prevalent in southern Europe, » Early symptoms include fever, Northern Africa, India, Asia, Caribbean coughing, wheezing, and dyspnea islands, South America, and small » Late symptoms include abdominal areas of the United States pain, nausea, vomiting, frequent » Associated with poor sanitation, throat clearing, dry , inadequate housing construction, “tingling throat,” appendicitis, and lack of access to medications , and obstruction 32 diagnosticsolutionslab.com GI-MAP® INTERPRETIVE GUIDE

» Can cause reactive arthritis » Consider anti-parasitic herbal treatments, gut immunity support, • Therapeutic Options and Considerations and the 5R Protocol (see Table 2) » Infections may be treated with » Look for and remove albendazole, mebendazole, sources of reinfection or ivermectin* » Consider anti-parasitic herbal Taenia spp. (Tapeworm) treatments, gut immunity support, and the 5R Protocol (see Table 2) • Epidemiology » Look for and remove » Fecal contamination of undercooked sources of reinfection pork (T. solium) or beef (T. saginata) » T. solium is found worldwide, but prevalent in communities Trichuris trichiura (Whipworm) who raise and eat • Epidemiology » T. saginata is prevalent in Africa, parts » Fecal contamination of produce of Eastern Europe, the Philippines, or person-to-person contact and Latin America where people » Prevalent in Asia, Africa, raise and eat raw beef South America, and rural • Clinical Implications southeastern United States » May be asymptomatic or • Clinical Implications present with mild symptoms » Most individuals are asymptomatic, » Symptoms include abdominal however diarrhea with mucus pain, nausea, weakness, and blood may occur in some increased appetite, loss of infected individuals appetite, headache, constipation, dizziness, diarrhea, , • Therapeutic Options and Considerations hyperexcitability, and anemia » Infections may be treated with • Therapeutic Options albendazole, mebendazole, and Considerations or ivermectin* » Infections may be treated with » Individuals presenting with IDA albendazole or praziquantel* may need iron supplementation » Consider anti-parasitic herbal treatments, gut immunity support, and the 5R Protocol (see Table 2) » Look for and remove sources of reinfection Microscopic cross section of a whipworm (Thichuris trichiura) RESEARCH. TECHNOLOGY. RESULTS. 33 INTESTINAL HEALTH MARKERS

DIGESTION » Chew thoroughly and relax at meal time » Pepsin Pancreatic Elastase 1 » Plant or pancreatic supplements Elastase 1 is a secreted exclusively by the , giving a » Digestive herbs direct indication of pancreatic function. » Bile salts Elastase 1 is unaffected by pancreatic » Taurine enzyme replacement therapy. » Consider underlying causes • Causes of Low Elastase 1: » Suppressed pancreatic function » Table 6. Staging of pancreatic » Hypochlorhydria, especially insufficiency based on fecal elastase-1. if H. pylori present Fecal Elastase-1 Result Clinical Significance » Cystic fibrosis Pancreatic » Low levels may be found < 200 ug/g insufficiency in vegetarians/vegans Decreased 200–500 ug/g • Common Approaches for Addressing pancreatic output Low Pancreatic Digestive Enzyme Levels: Normal > 500 ug/g » Digestive support with betaine HCL pancreatic output

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Steatocrit • Major Producers of β-glucuronidase are: » Bacteroides fragilis Fecal fats are normally emulsified by bile » Bacteroides vulgatus salts and absorbed in the small intestines. » Bacteroides uniformis High levels of fat in the stool may be an » Clostridium paraputrificum indication of maldigestion, malabsorption, or steatorrhea. » Clostridium clostridioforme » • Causes of Elevated Steatocrit: » Escherichia coli » Hypochlorhydria » » Maldigestion » » Malabsorption » » Pancreatic insufficiency(see elastase-1) » Staphylococcus » Bile salt insufficiency » Improper mastication • Clinical Indications of High β-glucuronidase: » Celiac disease » Dysbiosis in the colon or small • Therapeutic Approaches and intestinal bacterial overgrowth (SIBO) Considerations for High Fecal Fats: » Extremely elevated cases associated » Support digestion with betaine HCL with colon cancer risk » Pepsin » Problems with detoxification, especially » Digestive herbs or “bitters” estrogen (via glucuronidation pathway) » Bile salts » Overexposure to toxins or drugs » Taurine • Therapeutic Approaches and » Consider underlying causes of Considerations for Elevated malabsorption, such as celiac disease, β-glucuronidase: dysbiosis, or food sensitivities » Address dysbiosis, if present » Promote bacterial diversity with probiotics, fiber, prebiotics, and fermented foods ADDITIONAL GI MARKERS » Consider liver support such as milk thistle and calcium Beta-Glucuronidase D-glucarate, especially if patient is taking hormone replacement High levels of fecal beta-glucuronidase can or has increased cancer risk indicate unfavorable metabolic changes in » If there are no signs of dysbiosis on the the colon. Beta-glucuronidase may indicate GI-MAP, consider a SIBO breath test dysbiosis and interference with Phase II detoxification involving glucuronidation. RESEARCH. TECHNOLOGY. RESULTS. 35 INTESTINAL HEALTH MARKERS

Occult Blood Fecal Immune Response Immunochemical Testing (FIT) SIgA – Immunoglobulin A is the primary FIT is quantitative and directly measures immunoglobulin in the intestinal mucosa. the concentration of present It represents a “first line of defense” in in stool, rather than just the qualitative response to and pathogens in presence of hemoglobin. This test uses the GI and respiratory tracts. In addition to antibodies specific for human hemoglobin protecting against pathogens, SIgA plays a and therefore does not require dietary major role in helping to maintain balance restrictions or multiple samples, in the microbiome and protecting against significantly reducing the appearance exposure to food-derived antigens. of false positives. This method has Low Fecal SIgA – The gut immune system better detection of lower hemoglobin is suppressed. Investigate underlying concentrations than qualitative tests, causes, such as chronic dysbiosis, eliminating potential false negatives as well. antigen exposure, chronic stress, Literature suggests a result of 10 ug/g may immunocompromised patient, or even be indicative of potentially more serious protein malnutrition. conditions such as polyps or . A variety of ailments can cause • Therapeutic Approaches lower counts of , such as for Low SIgA Levels: , anal fissures, pathogenic » Address any chronic GI infection such as giardia, , and infections, if appropriate upper GI infections. » Address microbiome imbalances • Possible Causes of » Address chronic stress and Positive Occult Blood: adrenal health, if needed » Bleeding ulcer » Colostrum or immunoglobulins » Inflammatory bowel disease » Supplement with S. Boulardii » Cancer » GI mucosal support with glutamine » Intestinal polyps » Lactobacillus and » Upper GI bleeds that cause Bifidobacteria probiotics iron deficiency anemia » General immune support

• Common Approaches for » Essential fatty acids Addressing » Zinc » Identify source » Address other imbalances » Follow-up testing recommended on the GI-MAP

High Fecal SIgA – Elevated immune response to antigens in the GI tract.

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Investigate underlying causes, such as neutrophil infiltration to the gut mucosa. chronic dysbiosis, acute infections, acute Calprotectin is the gold standard marker stress, or food sensitivities. for the diagnosis and monitoring of inflammatory bowel disease. It is used • Therapeutic Approaches for High SIgA Levels: to differentiate IBD from . » Address GI infections » Address any food allergies • Possible Causes of and sensitivities Elevated Calprotectin » General immune support » Intestinal infections and pro- inflammatory dysbiosis Anti-gliadin SIgA – Gliadin is a component » Food allergens, toxins and certain of gluten, the protein found in and drugs (e.g., non-steroidal anti- other field grass grains such as barley, inflammatory drugs [NSAIDs]) malt, and rye. The presence of fecal anti- » Inflammatory bowel disease gliadin antibodies can indicate an immune » Polyps response (in the gut) to gluten in the » diet. Fecal anti-gliadin antibodies do not necessarily correlate with blood levels. » Colorectal cancer • Therapeutic Approaches High Anti-gliadin SIgA – Elevated immune and Considerations response to gliadin in the lumen of the gut. » Address possible causes of • Treatment: elevated calprotectin » Consider gluten elimination » Persistently elevated calprotectin may for a trial period indicate chronic inflammatory disease; » If patients have been gluten-free, further evaluation by a qualified consider hidden sources of gluten and medical professional is advised gliadin cross-reactive food such as » Consider anti-inflammatory dairy, corn, , millet, rice and yeast support (e.g., anti-inflammatory » Consider intestinal barrier diet, curcumin, omega-3 fatty support, including supplements acids, aloe, and ) such as L-glutamine, zinc Zonulin – Zonulin is a protein that opens carnosine, and colostrum intercellular tight junctions in the gut lining (the connections between epithelial cells that Inflammation make up the gastrointestinal lining). Zonulin increases intestinal permeability in the Calprotectin – Fecal calprotectin is the and and is considered a most studied marker of gastrointestinal biomarker for barrier permeability. inflammation. High calprotectin indicates

RESEARCH. TECHNOLOGY. RESULTS. 37 INTESTINAL HEALTH MARKERS

• Therapeutic Approach for » Promote a healthy intestinal barrier Elevated Intestinal Permeability: with L-glutamine, butyrate, essential » Address dysbiosis (pathogens and fatty acids, aloe vera, probiotics, zinc opportunistic microbe overgrowth, carnosine, slippery elm, marshmallow, lack of beneficial microbes) deglycyrrhizinated licorice » Eliminate gluten, address potential food sensitivities

ANTIBIOTIC RESISTANCE GENES

See Antibiotic Resistance Genes, Phenotypes for Helicobacter in the “” section of the interpretive guide (Figure 2).

Figure 4. Universal Microbiota Antibiotic Resistance Genes. The GI-MAP includes results for detection of antibiotic resistance genes in the microbiome. If an antibiotic resistance gene is present, then that class of antibiotics is designated POSITIVE for antibiotic resistance. A positive result for the presence of resistance genes for a given antibiotic indicates that the antibiotic is not an ideal choice for an antibiotic protocol. Antibiotic resistance genes apply to all of the microorganisms found in the fecal sample. Since microbes can rapidly share DNA under stress, the presence of antibiotic resistance in any organism is reason enough to avoid that drug class.

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TM GI-MAP DNA Stool Analysis

5895 Shiloh Rd, Ste 101 Patient: Ima Sample Accession: 20180212-0001 Collected: 2/10/2018 Alpharetta GA 30005 Received: 2/12/2018 DOB: 7/11/1981 877-485-5336 Completed: 1/9/2019

Pathogens Ordered by: Diane Farhi, MD Bacterial Pathogens Result Normal

The assays were developed and the perfomance characteristics determined by Diagnostic Solutions Laboratory. CLIA# 11D-2097795 Medical Director - Diane Farhi, MD

1

Download a GI-MAP® Sample Report at: diagnosticsolutionslab.com/tests/gi-map

References 1. Angol DC, Ocama P, Ayazika Kirabo T, Okeng A, Najjingo I, Bwanga F. Helicobacter pylori from Peptic Ulcer Patients in Uganda Is Highly Resistant to Clarithromycin and Fluoroquinolones: Results of the GenoType HelicoDR Test Directly Applied on Stool. BioMed research international. 2017;2017:5430723. 2. Segata N, Haake SK, Mannon P, et al. Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Biol. 2012;13(6):R42. 3. Fraser SL. Enterococcal infections. 2017; https://emedicine.medscape.com/article/216993-overview#a5. Accessed Jul 4, 2018. 4. Walsham NE, Sherwood RA. Fecal calprotectin in inflammatory bowel disease. Clinical and experimental . 2016;9:21-29.

RESEARCH. TECHNOLOGY. RESULTS. 39 Diagnostic Solutions laboratory Phone: 877-485-5336 Email: [email protected] Web: diagnosticsolutionslab.com

INTERPRETIVE GUIDE GI-MAP ® – Unparalleled DNA Based Stool Testing Our mission: to deliver innovative, accurate and clinically relevant diagnostic testing in a timely and cost-effective manner

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