GI Effects - Interpretive Guide · Disease (IBD). Research has also noted associations with...

Interpretive Guide

Introduction – GI EffectsSM

Proper gastrointestinal (GI) function is critical for overall health. The GI Effects profiles have been successful at helping clinicians evaluate underlying imbalances in the gut microbiome. In addition to digestion and absorption, the test profiles evaluate gut microflora status using a combination of molecular technology (commensal and opportunistic bacteria, and fungi), O & P (ova & parasites) and immunoassay (pathogenic organisms). Imbalances in any of these can significantly impact health.

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Table of ContentsIntroduction – GI EffectsSM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Predominant Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Opportunistic Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Yeast/Fungi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Parasitology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Adiposity Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Beneficial Short-Chain Fatty Acids (SCFA) . . . . . . . . . . . . . 7

Inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Immunology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Additional Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Digestion and Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . 10Pancreatic Elastase 1, Triglycerides, Putrefactive SCFA, LCFA, Cholesterol, and Total Fat Calculation

Add-on Profiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

T A X O N O M YMicrobiomeGI Effects tests utilize Polymerase Chain Reaction (PCR) technology to identify commensal and opportunistic bacteria and fungi. Parasites are identified by Ova and Parasites (O&P) methodology as well as Enzyme Immunoassay (EIA).

PCR utilizes probes that target specific, highly conserved segments of DNA, which allows identification of unique chosen sequences. These probes may be created at any level of the rank of organisms: Phylum, Class, Genus, or Species.

This DNA-based method has the ability to identify microbes with a single specimen. PCR has made it possible to accurately probe anaerobic bacteria, which make up the vast majority of gastrointestinal microbiota and which do not culture with standard aerobic culture environments.

Methodology: DNA Analysis, GC/MS, Microscopic, Colorimetric, Automated Chemistry, EIA

Ordering Physician:

1234 Main St.Anywhere, GA 30096

John Doe, MD

Accession #:

Patient:

Comment:Reprinted:

Age:

Reference #:

Date of Birth:

Sex:

A1309230356

Sample Report02/05/1962

10/30/2013Female

Fax:Telephone:

Date of Report:Date Received:Date Collected:

77044122377704464583

10/29/201309/23/201309/22/2013

2200 GI Effects Comprehensive Profile

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51

95% ReferenceRangeResults

Consistency = Formed/Normal

Predominant Bacteria E+007

Organisms are detected by DNA analysis. One colony forming unit (CFU) is equivalent to one bacterium. Each genome detected represents one cell, or one CFU. Results are expressed in scientific notation, so an organism reported as 2.5 E+007 CFU/gram is read as 25 million colony forming units per gram of feces.

Predominant Bacteria play major roles in health. They provide colonization resistance against potentially pathogenicorganisms, aid in digestion and absorption, produce vitamins and SCFA's, and stimulate the GI immune system. DNA probes allow detection of multiple species (spp.) within a genus, so the genera that are reported cover many species.

Obligate Anaerobes

>= 1.33.7Bacteroides spp.1.6 6.7

>= 1.07.6Clostridia spp.1.5 6.2

>= 1.12.3Prevotella spp.1.6 6.2

>= 1.17.1Fusobacteria spp.1.6 7.4

>= 1.02.4Streptomyces spp.1.6 5.8

>= 1.23.1Mycoplasma spp.1.7 6.2

Facultative Anaerobes

>= 1.23.4Lactobacillus spp.1.8 7.8

>= 1.84.9Bifidobacter spp.2.3 7.6

>= 1.16.7Escherichia coli (E. coli)1.7 7.7

Opportunistic Bacteria Expected Value

No clinically significant amounts. Opportunistic Bacteria may cause symptoms and be associated with disease. They can affect digestion and absorption, nutrient production, pH and immune state. Antibiotic sensitivity tests will be performed on all opportunistic bacteria found, although clinical history is usually considered to determine treatment since the organisms are not generally considered to be pathogens.

Georgia Lab Lic. Code #067-007 Laboratory Director: Robert M. David, PhDCLIA ID# 11D0255349 Testing Performed by Genova Diagnostics, Inc. 3425 Corporate Way, Duluth, GA 30096New York Clinical Lab PFI #4578Florida Clinical Lab Lic. #800008124 Page 2


Ordering Physician:

1234 Main St.Anywhere, GA 30096

John Doe, MD

Accession #:

Patient:

Comment:Reprinted:

Age:

Reference #:

Date of Birth:

Sex:

A1309230356

Sample Report02/05/1962

10/30/2013Female

Fax:Telephone:

Date of Report:Date Received:Date Collected:

77044122377704464583

10/29/201309/23/201309/22/2013


G1234567Order #:

51


Consistency = Formed/Normal

Predominant Bacteria E+007

Organisms are detected by DNA analysis. One colony forming unit (CFU) is equivalent to one bacterium. Each genome detected represents one cell, or one CFU. Results are expressed in scientific notation, so an organism reported as 2.5 E+007 CFU/gram is read as 25 million colony forming units per gram of feces.

Predominant Bacteria play major roles in health. They provide colonization resistance against potentially pathogenicorganisms, aid in digestion and absorption, produce vitamins and SCFA's, and stimulate the GI immune system. DNA probes allow detection of multiple species (spp.) within a genus, so the genera that are reported cover many species.

Obligate Anaerobes

>= 1.33.7Bacteroides spp.1.6 6.7

>= 1.07.6Clostridia spp.1.5 6.2

>= 1.12.3Prevotella spp.1.6 6.2

>= 1.17.1Fusobacteria spp.1.6 7.4

>= 1.02.4Streptomyces spp.1.6 5.8

>= 1.23.1Mycoplasma spp.1.7 6.2

Facultative Anaerobes

>= 1.23.4Lactobacillus spp.1.8 7.8

>= 1.84.9Bifidobacter spp.2.3 7.6

>= 1.16.7Escherichia coli (E. coli)1.7 7.7

Opportunistic Bacteria Expected Value

No clinically significant amounts. Opportunistic Bacteria may cause symptoms and be associated with disease. They can affect digestion and absorption, nutrient production, pH and immune state. Antibiotic sensitivity tests will be performed on all opportunistic bacteria found, although clinical history is usually considered to determine treatment since the organisms are not generally considered to be pathogens.


· · · · · 3

The Latest Advancement in Comprehensive Stool Analysis

Predominant BacteriaGI Effects detects microorganisms by DNA analysis. Each genome detected represents one microorganism, or one CFU. Standard microbiological results are reported as Colony-Forming Units per gram of feces (CFU/gram). Because there are very large numbers of microorganisms in stool, results are expressed in standard scientific notation. For example, Bacteroides spp. may be reported as 2.57 E7, or 2.5 x 107, or 25,000,000 CFU/gram, which is read as 25 million CFU per gram of feces.

Humans have a conserved set of gut microbiota that is shared among individuals, though each person has their own distinct and highly variable microbiota. The commensal gut microbiota interacts extensively with the host, influencing multiple metabolic and physiological functions, such as: regulating the development of the gut, producing Short-Chain Fatty Acids (SCFA), com-municating with and mentoring the immune system, preventing growth of harmful species, producing vitamins (such as biotin and vitamin K), neutralizing toxins, stimulating the intestinal immune system, and modulating gastrointestinal hormone production, oxidative response, and barrier function.

Not surprisingly, levels of total commensal bacteria and/or individual bacteria have been correlated with several conditions, such as Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD). Research has also noted associations with meta-bolic conditions, including obesity, diabetes, and non-alcoholic liver disease. Additionally, the intestinal microflora are of central importance in preventing colonization by pathogens, termed “colonization resistance.” 3

Though numerous published research and review papers have described dysbiosis as an imbalance or deficiency of commensal bacteria, there is currently no standard definition of dysbiosis.76-88 Research identifies three primary types of dysbiosis: transient, disrupting, or persistent.89

Low or Unbalanced Commensal Bacteria – Potential Source or Association

• Dysbiosis: Commensal bacteria should be balanced and in adequate amounts in the healthy gut. A gut with low levels of all commensal bacteria may be considered dysbiotic.89

f Unbalanced or low commensal bacteria has been associated with low carbohydrate or fiber intake, antibiotic or botanical intake, unbalanced probiotic or prebiotic supplementation, and inflammatory conditions

Therapeutic Considerations

• Add probiotics

• Add prebiotics to feed the bacteria that are living in the gut. Examples include: psyllium, oat bran, oligofructose, xylooligosaccharide, inulin, beta-glucan, and/or arabinogalactan.91 Inulin and oligofructose favor the growth of indigenous lactobacilli and/or bifidobacteria.75

• Improve diet. Increased intake of fibers and whole, complex carbohydrates can increase levels of commensal bacteria. Vegans and vegetarians have greater amounts of total commensal bacteria. Individuals on a low-carbohydrate, low-fiber diet may experience a drop in levels of commensal bacteria. High-fiber foods may exacerbate patient symptoms and should be introduced gradually.76

4 · · · · ·

Opportunistic BacteriaOpportunistic-bacterial overgrowth may be exacerbated by low commensal bacteria, pathogen or parasite infection, poor diet, an-tibiotic use, or lowered gut immunity. Opportunistic bacteria are often asymptomatic, self-limiting, and not normally pathogenic. The presence of fecal opportunistic bacteria may be clinically rel-evant in patients with bacterial gastroenteritis, including: traveler’s diarrhea,92-96 food poisoning,97 IBD,98 and/or IBS.99

Salmonella, Aeromonas, Yersinia enterocolitica, and Vibrio have been shown to play a causative role in gastroenteritis and food poisoning. Vibrio and Citrobacter have been detected in diar-rhea stools. Yersinia enterocolitica has been found in stools of IBD patients.


• Consult the microbial sensitivity done to determine the sensitivity or resistance of identified bacteria to pharmaceutical and active botanical agents if included with report. Bacteria found to be sensitive are marked as “S”.

• Evaluate level of commensal bacteria; consider probiotic therapy and immune assessment

Yeast/Fungi The Kingdom Fungi is divided into subkingdoms and phyla. A fungus is a member of a large group of organisms that includes yeasts and molds. Colonic fungi generally coexist inside the host without detriment.

Opportunistic fungi are associated with gastrointestinal symptoms and may be considered pathogenic, especially in immune-compromised individuals. Mycosis is a fungal infection, which can lead to an imbalance of microorganisms within the gut, or another affected area. Groups at increased risk of fungal infections include those with compromised immune systems, those on steroids, people with diabetes, or the very young and very old.

Colonic fungi assessed in the GI Effects profile include: Candida spp., Saccharomyces spp., Geotrichum, and Rhodotorula spp. Candida spp. is a normal inhabitant of the gastrointestinal flora. Saccharomyces spp. includes both S. boulardii and S. cerevisiae.

Potential Symptoms or Association

• General symptoms may include gastric pain, nausea and vomiting, gas and bloating. Overgrowth is associated with immune reactions to foods (consider intestinal permeability), imbalance in gut microflora, and opportunistic bacterial infection.

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Table 1 . Common Parasitic Protozoans Parasitic Protozoans Symptoms Therapeutic Considerations

Blastocystis hominisTransmission: Unknown; consider contaminated food or water, or exposure to infected animals suspected .

Watery or loose stools, diarrhea, abdominal pain, anal itching, weight loss, constipation, fatigue, and excess flatulence have been reported in persons with Blastocystis infection . Many people are asymptomatic .

The clinical significance of Blastocystis spp . is controversial . See www.dpd.cdc.gov/dpdx/HTML/Blastocystis.htm

Cryptosporidium spp.Transmission: Fecal contamination of food or water, including swimming pools and municipal water supplies .

Patients will be symptomatic or present with diarrhea varying from mild to severe, abdominal cramping, weight loss, anorexia, nausea, vomiting, flatulence, malaise, and mild fever .

Most people who have healthy immune systems will recover without treatment . Diarrhea can be managed by drinking plenty of fluids to prevent dehydration . Immunosuppression increases infection severity . See www.dpd.cdc.gov/dpdx/HTML/Cryptosporidiosis.htm

Dientamoeba fragilisTransmission: Unknown; often associated with pinworm infection or fecal contamination .

Patients will be asymptomatic or present with diarrhea, nausea, and vomiting; abdominal tenderness is possible .

There is no consensus as to best clinical practice; goal is eradication of parasite . See www.dpd.cdc.gov/dpdx/HTML/Dientamoeba.htm

Entamoeba coli, Entamoeba histolytica and Entamoeba disparTransmission: Contaminated food or water, pets, sexual contact .

More common in people who live in tropical areas with poor sanitary conditions . It can be a pathogenic amoeba .

Several protozoan species in the genus Entamoeba colonize humans, but not all of them are associated with disease . Entamoeba histolytica is well recognized as a pathogenic amoeba, associated with intestinal and extra-intestinal infections . Only about 10% to 20% of people who are infected with E. histolytica become sick . A severe form of E. histolytica is associated with stomach pain, bloody stools, and fever (may resemble ulcerative colitis) . E. dispar is non-pathogenic .

Only one antibiotic is used in non-symptomatic E. histolytica infection; two antibiotics if patients are symptomatic . See www.dpd.cdc.gov/dpdx/HTML/IntestinalAmebae.htm and www.dpd.cdc.gov/dpdx/HTML/Amebiasis.htm

Giardia lambliaTransmission: Contaminated water, food, or fecal-oral transmission . G. lamblia is the leading cause of intestinal parasitic infection in the US .See www.dpd.cdc.gov/dpdx/HTML/Giardiasis.htm

Patients can be asymptomatic . If symptomatic, will present with acute to chronic diarrhea with bloating, intestinal malabsorption, and steatorrhea . Giardiasis has been associated with agammaglobulinemia, chronic pancreatitis, achlorhydria, and cystic fibrosis .

Several prescription drugs are available to treat giardiasis . See emedicine.medscape.com/article/176400-clinical


• Consider patient symptoms, degree of infection, and overall immune status.

• Reduce intake of refined carbohydrates and sugars; avoid FOS powder

• Consult the microbial sensitivity done to determine the sensitivity or resistance of identified fungi to pharmaceutical and active botanical agents if included with report. Fungi found to be sensitive are marked as “S.”

ParasitologyThe GI Effects profile utilizes the accepted gold standard for parasite detection, the microscopic Ova & Parasites (O & P) exam. O & P approaches have the highest proven diagnostic and clinical utility for parasite detection. While governing bodies, such as the Centers for Disease Control, recommend a minimum of three samples on at least three separate days for the highest parasite detection, literature suggests that > 90% of enteric parasitic infections are detected in a single stool sample using O & P collection. In addition, Cryptosporidium, Giardia lamblia, and Entamoeba histolytica/dispar are assessed by EIA.

All organisms identified on the 2100 profile by PCR may be identified by O & P.

A1309230356Sample Report

Ordering Physician: John Doe, MDComment:

Date of Report: 10/29/201310/30/2013Reprinted:



Yeast/Fungi Expected Value

No clinically significant amounts. Yeast/Fungi Yeast overgrowth has been linked to many chronic conditions, in part because of antigenic responses in some patients to even low rates of yeast growth. Potential symptoms include diarrhea, headache, bloating, atopic dermatitis and fatigue. Positives are reported as +1, +2, +3 or +4 indicating >100, >1000, >10000 or >100000 pg DNA/g.

ParasitologyParasitology Parasite Recovery: Literature suggests that >90% of enteric parasitic infections are detected in a sample from a single stool collection. Increased sensitivity results from the collection of additional specimens on separate days. Parasites have been detected in 20-24% of U.S. patients with mild to moderate GI symptoms.

Microscopic Exam Results:*

Dientamoeba fragilis: Few

Parasitology EIA Tests:In Range Out of Range

Cryptosporidium Negative

Giardia lamblia Negative

E. histolytica/dispar Negative

*Indicates testing performed by Genova, Inc. 63 Zillicoa St., Asheville, NC 28801-1074A. L. Peace-Brewer, PhD, D(ABMLI), Lab Director · CLIA Lic. #34D0655571 · Medicare Lic. #34-8475

Adiposity Index Expected Value

The Adiposity Index is derived by using DNA probes that detect multiple genera of the phyla Firmicutes and Bacteroidetes. Abnormalities of these phyla may be associated with increased caloric extraction from food.

<= 8070Firmicutes % %

>= 2030Bacteroidetes % %







Yeast/Fungi Expected Value

No clinically significant amounts. Yeast/Fungi Yeast overgrowth has been linked to many chronic conditions, in part because of antigenic responses in some patients to even low rates of yeast growth. Potential symptoms include diarrhea, headache, bloating, atopic dermatitis and fatigue. Positives are reported as +1, +2, +3 or +4 indicating >100, >1000, >10000 or >100000 pg DNA/g.

ParasitologyParasitology Parasite Recovery: Literature suggests that >90% of enteric parasitic infections are detected in a sample from a single stool collection. Increased sensitivity results from the collection of additional specimens on separate days. Parasites have been detected in 20-24% of U.S. patients with mild to moderate GI symptoms.

Microscopic Exam Results:*

Dientamoeba fragilis: Few

Parasitology EIA Tests:In Range Out of Range

Cryptosporidium Negative

Giardia lamblia Negative

E. histolytica/dispar Negative

*Indicates testing performed by Genova, Inc. 63 Zillicoa St., Asheville, NC 28801-1074A. L. Peace-Brewer, PhD, D(ABMLI), Lab Director · CLIA Lic. #34D0655571 · Medicare Lic. #34-8475

Adiposity Index Expected Value

The Adiposity Index is derived by using DNA probes that detect multiple genera of the phyla Firmicutes and Bacteroidetes. Abnormalities of these phyla may be associated with increased caloric extraction from food.

<= 8070Firmicutes % %

>= 2030Bacteroidetes % %


O&P Assessment Microscopically Detects Parasites and their Eggs

from a Stool Sample and Provides Clinically

Actionable Results

6 · · · · ·







Beneficial SCFA

Beneficial SCFA Short chain fatty acids (SCFA) are produced by bacterial fermentation of dietary polysaccharides and fiber. The product, N-butyrate, is taken up and used to sustain the normal activity of colonic epithielial cells. Butyrate has been shown to lower the risk of colitis and colorectal cancer. A healthy balance of GI microbes depends on production of SCFA by one specie to allow the normal growth of another one in a complex cross-feeding network.

>= 3567Total SCFA53

mM/g

>= 3.99.3n-Butyrate5.2

mM/g

47-7761Acetate % %7152

7-3014n-Butyrate % %2510

10-2924Propionate % %2513

0.4-4.61.8Valerate % %3.61.0

InflammationInflammation Lactoferrin, an iron-binding glycoprotein, is released in IBD but not in non-inflammatory IBS. High levels are found in Crohn's, UC or infection. WBC's are elevated in general inflammation/infection. Mucus is often visualized in acute GI inflammation.

<= 6.32.6Lactoferrin3.1

ug/mL

NegativeWBCs Negative-Rare

NegativeMucus Negative

ImmunologyImmunology High fecal sIgA indicates immune system reactions to the presence of antigens from bacteria, yeast or other microbes. Low sIgA can result from stress or malnutrition.

5-16180Fecal sIgA mg/dl14420








Beneficial SCFA

Beneficial SCFA Short chain fatty acids (SCFA) are produced by bacterial fermentation of dietary polysaccharides and fiber. The product, N-butyrate, is taken up and used to sustain the normal activity of colonic epithielial cells. Butyrate has been shown to lower the risk of colitis and colorectal cancer. A healthy balance of GI microbes depends on production of SCFA by one specie to allow the normal growth of another one in a complex cross-feeding network.

>= 3567Total SCFA53

mM/g

>= 3.99.3n-Butyrate5.2

mM/g

47-7761Acetate % %7152

7-3014n-Butyrate % %2510

10-2924Propionate % %2513

0.4-4.61.8Valerate % %3.61.0

InflammationInflammation Lactoferrin, an iron-binding glycoprotein, is released in IBD but not in non-inflammatory IBS. High levels are found in Crohn's, UC or infection. WBC's are elevated in general inflammation/infection. Mucus is often visualized in acute GI inflammation.

<= 6.32.6Lactoferrin3.1

ug/mL

NegativeWBCs Negative-Rare

NegativeMucus Negative

ImmunologyImmunology High fecal sIgA indicates immune system reactions to the presence of antigens from bacteria, yeast or other microbes. Low sIgA can result from stress or malnutrition.

5-16180Fecal sIgA mg/dl14420


· · · · · 7

Adiposity IndexIn adults, the majority of gut bacteria are members of two primary phyla, Bacteroidetes and Firmicutes. The Firmicutes de-scribed in the report consists of Clostridia spp., Lactobacillus spp., Mycoplasma spp., and Bacillus spp. The Bacteroidetes consist of Bacteroides spp., and Prevotella spp.

Obesity has been associated with substantial changes in gut-microbiota composition, and the relative proportions of Firmicutes to Bacteroidetes.90

Beneficial Short-Chain Fatty Acids (SCFA)Total SCFA, n-Butyrate, n-Butyrate%, Acetate%, Propionate%, Valerate%

Commensal gut bacteria produce SCFA (including acetate, propionate, and butyrate) from dietary carbohydrates, specifically resistant starch and fiber (prebiotics).64 SCFA contribute to normal bowel functions (such as maintenance of the intestinal barrier) and prevent pathology. SCFA, and specifically n-butyrate, serve as fuel for the colonocytes.

No optimal level of SCFA has been identified; higher values have generally been associated with decreased GI disease. High-fiber diets have been linked with reduced risk of colorectal cancer, as well as playing a role in reducing cholesterol and blood sugar.65-73

Research has identified that SCFA levels can be affected by a variety of factors, including: diet, fecal ammonia, obesity, inflammation, race, environment, and gender. Low SCFA may indicate inadequate fiber intake, an unbalanced commensal bacterial population, or impaired bowel health.

SCFA and n-Butyrate Outside of the Reference Range – Potential Source or Association

• Decreased carbohydrate or fiber intake64

• Low anaerobic or commensal bacteria: dysbiosis

• Altered levels of SCFA have been associated with compromised mucosal health and increased colonic inflammation


• Consider prebiotic supplementation: psyllium, oat bran, oligofructose, inulin, xylooligosaccharide, beta-glucan, or arabinogalactan. Inulin and oligofructose have been found to stimulate colonic production of SCFA.75

• Increase dietary carbohydrate and fiber intake (fruits, vegetables, legumes, and whole grains)

• Evaluate and treat abnormalities of commensal gut bacteria

InflammationLactoferrin , WBC, and Mucus

Lactoferrin is an iron-binding glycoprotein released from neu-trophils during inflammation. It is a marker of leukocyte activ-ity, and as such, suggests the presence of an active inflammatory process in the gut.

Causes of Elevation

• Significant mucosal inflammation from bacterial or parasitic infection

• Active diverticulitis or IBD

• Colorectal cancer


• Identify and address root cause of inflammation; may require further testing:

f Microbiology and parasitology to rule out pathogenic organisms

f Calprotectin

f Eosinophil protein X

f Intestinal Permeability Assessment

• Rule out food sensitivities

• Add anti-inflammatory and mucosal support

f Anti-inflammatory herbs and nutrients, e.g. turmeric, ginger, EPA/DHA, quercetin, antioxidants

f Mucosal support nutrients, e.g. vitamin A, zinc, folic acid, Aloe vera, licorice, L-glutamine, butyrate, N-Acetyl glucosamine, slippery elm

8 · · · · ·

Test Interferences

Colostrum has a high concentration of lactoferrin, so infants breast feeding or those supplementing with colostrum could show false positives.

WBCs and Mucus can indicate intestinal inflammatory reactions.

ImmunologyFecal Secretory Immunoglobulin A (SIgA)

Fecal SIgA is the chief antibody in the membranes of the gastro-intestinal and respiratory tracts. It is the most abundant antibody produced in the intestine, secreted in gram amounts across the intestinal mucosa. Secretory IgA is resistant to degradation in the harsh environment of the gastrointestinal tract and regulates the balance of commensal bacteria in the gut, preventing colonization of pathogens and regulating epithelial barrier function.44, 45 Levels of SIgA that are abnormally elevated or depressed can signal alterations in gastrointestinal immunity. Low or absent SIgA may increase susceptibility to pathogens and also produce a leaky gut barrier, contributing to increased risk of food allergy.43, 103, 104 In contrast, elevated levels may represent a normal transient rise in response to a microbial assault or a chronic pathological state.

Elevated SIgA – Potential Source or Association

• Normal immune response to pathogenic organisms

• Chronic elevations have been found in intractable gastrointestinal infections, atopic dermatitis, and colorectal cancer

Depressed SIgA – Potential Source or Association

• Immune-compromised individuals

• Dysbiosis 44, 45

• Partial or primary selective IgA deficiency


• Eradicate pathogen or other infectious agent, if present 46

• Consider probiotic supplementation47-50

• Further testing may be warranted for persistent elevation

• Rule out food sensitivities, consider elimination diet or IgG food sensitivity testing

• Overall immune system support

• Mucosal and anti-inflammatory support with:51-60

f Nutrients: vitamin A, zinc, folic acid, L-glutamine, butyrate, N-acetyl glucosamine, fatty acids

f Diet (whey protein, increased fiber)

f Botanicals (slippery elm, marshmallow root, Aloe vera, licorice, curcumin)

· · · · · 9

Additional TestsFecal pH

Fecal pH indicates the relative acidity or alkalinity of the colonic environment. The pH of the stool is not directly influenced by hydrochloric acid, which maintains the pH of the stomach. Stool pH is influenced by fiber and food constituent intake, fermen-tative processes, bacterial populations, stool transit time, and antibiotic therapy.105–109

While a mildly acidic pH is preferable, extremes in stool pH—either too acid or alkaline—present challenges to colonic and systemic health.

Depressed (More Acidic) pH – Potential Source or Association

• Decreased commensal bacteria and overgrowth of pathogenic bacteria, especially of the Enterobacteriaceae Family100

• Associated with carbohydrate maldigestion/malabsorption, osmotic laxatives, rapid transit time, or small bowel bacterial overgrowth101


• Address causes of diarrheal syndromes: malabsorption, viral or bacterial toxins, and medications

• Support digestion and absorption; make appropriate dietary changes

• Rule out disaccharide intolerance (Lactose Intolerance Breath Test)

• Rule out digestive alterations due to food sensitivities (Allergy Antibody Assessment)

• Rule out malabsorption (Intestinal Permeability Assessment)

• Rule out celiac disease

Elevated (More Alkaline) pH – Potential Source or Association

• Maldigestion due to inadequate stomach acid, excessive protein consumption, slow transit time/constipation, and inadequate dietary fiber

• Limited research has identified lower commensal bacteria in alkaline feces100


• Limited research indicates that prebiotics may lower stool pH102

• Evaluate commensal bacteria and short-chain fatty acids for balance and adequate levels, especially n-butyrate

• Ensure adequate dietary fiber, prebiotic and/or probiotics

RBCs

Potential Source or Association

• Bleeding in lower GI from hemorrhoids, intestinal polyps, or tears around the anus due to constipation


• Bowel support to normalize stool pattern

• Consider Occult Blood test

• Consider colonoscopy to identify source; treat accordingly

ColorStool color is generally related to diet or medications, though it can also be an indication of health conditions.

• Healthy stools are a brown to dark brown color

• Green coloring can be from bile. This can show up in greater concentrations in diarrheal stools.

• Light-colored stools can indicate a lack of bile. Some antacids that contain aluminum hydroxide may also lead to lighter stools.

• Bright red can indicate bleeding from the rectum. Beets or food dye can also cause stools to turn red.

• Black stools may identify blood from further up the GI tract, such as the small intestine or stomach. Certain medications may produce a dark stool. These include Pepto-Bismol® (a bismuth subsalicylate), iron supplements, or foods such as black licorice.

ConsistencyPatients self-report consistency with ranges from diarrhea to hard/constipated.







Additional TestsAdditional Tests pH is influenced by numerous factors, but it is strongly related to the bacterial release of pH-lowering organic acids and pH-raising ammonia. Positive RBCs can signify GI tract bleeding. Color (other than brown) abnormalities can be due to upper GI bleeding, or bile duct blockage, steatorrhea or antibiotic use.

5.7-7.16.1pH6.95.9

NegativeRBCs Negative

BrownColor

DigestionDigestion Pancreatic elastase 1 levels below 100 are strongly correlated with severe pancreatic insufficiency; levels of 100-200 identify moderate pancreatic insufficiency. High triglycerides signify fat maldigestion. Putrefactive SCFA are a result of bacterial fermentation of undigested protein. High numbers of vegetable fibers indicate maldigestion.

ug/g> 100245Elastase 1200

<= 181112Triglycerides119

mg/dL

<= 7.42.6Putrefactive SCFA4.4

mM/g

RareVegetable Fibers None-Few

AbsorptionAbsorption High LCFA indicates fat malabsorption due to pancreatic or biliary insufficiency, or acute bacterial infection that produces intestinal cell destruction. High total fat usually signals malabsorption, as does elevated fecal cholesterol.

<= 15.1H23.6LCFAs9.1

mmol/L

<= 18.9H28.2Total Fat12.9

mmol/L

mg/dL<= 191129Cholesterol142

*UC = Unable to Calculate

Decisions involving diagnosis and treatment are the responsibility of the clinician.








Additional TestsAdditional Tests pH is influenced by numerous factors, but it is strongly related to the bacterial release of pH-lowering organic acids and pH-raising ammonia. Positive RBCs can signify GI tract bleeding. Color (other than brown) abnormalities can be due to upper GI bleeding, or bile duct blockage, steatorrhea or antibiotic use.

5.7-7.16.1pH6.95.9

NegativeRBCs Negative

BrownColor

DigestionDigestion Pancreatic elastase 1 levels below 100 are strongly correlated with severe pancreatic insufficiency; levels of 100-200 identify moderate pancreatic insufficiency. High triglycerides signify fat maldigestion. Putrefactive SCFA are a result of bacterial fermentation of undigested protein. High numbers of vegetable fibers indicate maldigestion.

ug/g> 100245Elastase 1200

<= 181112Triglycerides119

mg/dL

<= 7.42.6Putrefactive SCFA4.4

mM/g

RareVegetable Fibers None-Few

AbsorptionAbsorption High LCFA indicates fat malabsorption due to pancreatic or biliary insufficiency, or acute bacterial infection that produces intestinal cell destruction. High total fat usually signals malabsorption, as does elevated fecal cholesterol.

<= 15.1H23.6LCFAs9.1

mmol/L

<= 18.9H28.2Total Fat12.9

mmol/L

mg/dL<= 191129Cholesterol142

*UC = Unable to Calculate

Decisions involving diagnosis and treatment are the responsibility of the clinician.


10 · · · · ·

Digestion and AbsorptionMalabsorption and maldigestion can have a significant impact on nutrient status and overall health. Maldigestion is the impaired breakdown of food components; malabsorption is impaired mucosal uptake and transport of adequately digested nutrients.1 Impaired digestion and absorption can lead to a loss of nutrients, resulting in possible nutrient deficiencies. Further assessments may include evaluation of nutritional status.2

Pancreatic Elastase 1 (PE1)

Pancreatic Elastase 1 is a proteolytic enzyme secreted by the exocrine pancreas, with a direct correlation to pancreatic function and a strong correlation with the gold-standard test for pancreatic insufficiency (secretin-pancreozymin test). PE1 is a stable marker; it is not degraded during intestinal transit, is not greatly affect-ed by changes in intestinal transit time, and is not affected by pancreatic enzyme-replacement therapy. Pancreatic exocrine insuf-ficiency can result in maldigestion and malabsorption, leading to abdominal pain, steatorrhea, malnutrition, nutrient deficiencies, and weight loss. The test may have a lower sensitivity in children with mild pancreatic insufficiency.4

PE-1 values > 200 mcg/g rule out significant pancreatic dysfunction; a value between 100 to 200 mcg/g suggests moderate pancreatic insufficiency; and < 100 mcg/g indicate severe pancreatic insufficiency.5, 6


• Exocrine pancreatic insufficiency has been noted in gastrointestinal and pancreatic surgical resections, chronic pancreatitis, celiac disease, gallstones or post-cholecystectomy, chronic inflammatory intestinal disorders, alcohol excess, and cystic fibrosis7-11

• Diabetes is associated with increased risk of pancreatic insufficiency; about 50% in type 1 and 33% in type 2. (If PE1 < 50 mcg/g consider evaluating endocrine and exocrine functions.)12

• Decreased meat intake, vegetarian or vegan diets have all been associated with reductions in fecal PE 113, 14

• Pancreatic function may decrease with age15


• Patients with pancreatic exocrine insufficiency warrant further investigation to determine the ‘root cause’ of the dysfunction; support with pancreatic enzyme-replacement therapy until cause is determined, PE1 levels normalize, and symptoms improve

• Support with plant or digestive enzymes or digestive herbs16-19

• Evaluate fecal total fat, triglycerides, cholesterol, and LCFAs19

• Consider a full nutritional assessment; research has found impaired pancreatic function to be associated with greater deficiencies and impairment of antioxidant status

f A number of studies have demonstrated that chronic-pancreatitis patients have a compromised antioxidant status, which may be associated with increased oxidative state

Putrefactive SCFAIntestinal proteins (from food, albumin, blood, muscle, intesti-nal secretions and exudate) are metabolized by gut bacteria. Gut bacteria ferment proteinaceous material into the putrefactive SCFA,31, 32 primarily isovalerate, valerate, and isobutyrate. On a normal mixed diet, it is generally the amount of protein in the diet that determines the level of products of protein digestion. Only small amounts of these products of protein digestion are usually found in a healthy colon.


• Increased protein within the intestinal lumen can be due to various factors:

f Hypochlorhydria or pancreatic insufficiency;33 approximately 30% of the elderly have low secretion of hydrochloric acid by gastric parietal cells. Acid-blocking medications and dietary supplements may increase the gastric pH.34

· · · · · 11

f Elevation of gastric pH may increase the risk for food reactions by hindering protein breakdown35-37

f Protein maldigestion may be due to pancreatic insufficiency or pancreatitis38, 39

f Excessive protein intake

f Gastrointestinal disease resulting from increased protein material in the colon (exudations, mucosal desquamation, bleeding) 40


• Ensure appropriate stomach-acid concentration. Consider support with betaine HCl or reducing acid-blocking medications.34

• Consider appropriate digestive enzyme support if digestive enzymes are inadequate (review Pancreatic Elastase 1)

• Evaluate levels of dietary protein intake and increase carbohydrate41

f Fructooligosaccharides (FOS) decreased fecal protein catabolites in one study41

Quantification of Triglycerides, LCFA, Cholesterol, and Total Fat Calculation

Dietary fats are digested by pancreatic enzymes in the small intestine. Increased fecal fat has been correlated with fat malab-sorption. The GI Effects test provides a quantitative measure of triglycerides, LCFA, and cholesterol. Total fat is then established by a calculation. The extracted lipids are analyzed enzymatically using a colorimetric method. The quantitative results have been found to correlate well (r2 = 0.72) with the gold standard of fat assessment (the three-day fecal fat test).20


• Patients with steatorrhea—passage of pale, bulky, and malodorous stools, indicating maldigestion and/or malabsorption issues; non-specific signs and symptoms may include: fatigue, unexplained anemia, nutrient deficiencies, and weight loss

• Fat malabsorption can be associated with: diarrhea, intestinal dysbiosis, parasites, IBS, IBD, gluten intolerance, food intolerances, celiac disease, hypochlorhydria, gastric by-pass, pancreatic or bile salt insufficiency, excess alcohol intake, ileal resection, and/or chronic non-steroidal anti-inflammatory drug (NSAID) usage21

• Bacterial overgrowth may limit fat absorption22

• Medications or foods designed to bind and eliminate fats (orlistat (Xenical, Alli) or olestra [Olean])23,24-26

• High fat diet27

• Acidic intestinal pH and bacterial overgrowth may also prevent normalization of fat digestion19


• Consider support with supplementary plant or lipase enzymes, betaine hydrochloride (HCl), digestive herbs, bile salts or cholagogues (taurine or glycine), if indicated2, 28

• Discontinue medications or foods that bind fats

• Assess essential fatty acids, vitamins (especially fat-soluble), and minerals29, 30

SensitivitiesSensitivity testing is done on all identified opportunistic bacteria and fungi targets. Results indicate the susceptibility or resistance to prescriptive agents, and the level of inhibition from botanical and non-absorbed antifungal agents.

12 · · · · ·

Table 2 . Pathogenic Bacteria by EIAPathogen Symptoms Therapeutic Considerations

Campylobacter spp.Transmission: Consumption of contaminated food (particularly poultry), water, or contact with infected animals (particularly cats and puppies) .

Symptoms include: diarrhea (often bloody), abdominal cramps, and fever . Illness typically lasts one week and may be serious in immunocompromised patients . Campylobacter. jejuni infection has been associated with the onset of Guillain-Barré syndrome (GBS) .

Patients generally recover without any specific treatment . They should drink extra fluids throughout the duration of diarrheal episodes . CDC review is at www.cdc.gov/nczved/divisions/dfbmd/diseases/campylobacter/

Clostridium difficileTransmission: Shed in feces .

Symptoms include: cramping, lower abdominal pain/tenderness, fever, watery diarrhea, loss of appetite, and nausea . It is a common cause of antibiotic-associated diarrhea (AAD) .

In about 20% of patients, C. diff infection will resolve within 2 to 3 days of discontinuing the antibiotic to which the patient was previously exposed . CDC review is at www.cdc.gov/HAI/organisms/cdiff/Cdiff_faqs_HCP.html#a9

Shiga toxin E. coli Transmission: Consumption of contaminated food, unpasteurized (raw) milk, water that has not been disinfected, contact with cattle or the feces of infected people . STEC stands for shiga toxin-producing Escherchia coli (STEC) .

The symptoms vary but may include abdominal cramping, watery or bloody diarrhea, and vomiting .

The infection can be self-limiting . Rehydrate, and consider pre-and probiotics to support infection resolution . Treatment is based on the site and severity of infection, and STEC status .CDC review at www.cdc.gov/ecoli/index.html . Also see www.cdc.gov/ecoli/clinicians.html

Helicobacter pyloriTransmission: Is incompletely characterized . Person-to-person transmission is most commonly implicated with fecal/oral, oral/oral, or gastric/oral pathways .

Symptoms include: acute gastritis with abdominal pain, nausea, and vomiting . Non-ulcer dyspepsia is common . Development of severe H . pylori disease is partially determined by the virulence of the infecting strain .

Conventional recommendation is polypharmacy: antibiotics and proton-pump inhibitors (PPIs) . See www.acg.gi.org . Botanical anti-H. pylori formulas may prove helpful . See www.cdc.gov/ulcer/keytocure.htm .

Add-on ProfilesPathogenic Bacteria by EIA

Diagnostic utility is best achieved by applying diagnostic assessment for these pathogens within an appropriate clinical differential, i.e. in a symptomatic patient for whom there is a high index of suspicion for infection.

· · · · · 13

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107. Ahmed R et al. Fermentation of dietary starch in humans. Am J Gastroenterol. 2000 Apr;95(4):1017-20.

108. Hoverstad T et al. Influence of oral intake of seven different antibiotics on faecal short-chain fatty acid excretion in healthy subjects. Scand J Gastroenterol. 1986 Oct;21(8):997-1003.

109. Oufir LE et al. Relationships between transit time in man and in vitro fermentation of dietary fiber fiber by fecal bacteria. 2000 Aug;54(8):603-9.

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Gi Effects Profiles are Especially Ideal for Patients with:

GI Effects Stool Profiles

• See link below* for the following:

f # 2200 GI Effects

f # 2205 GI Effects Microbial Ecology Profile

f # 2110 GI Effects Mycology Profile

f # 2120 GI Effects Chemistries Profile

Specimen Requirements

• # 2200 Stool, 3 tubes, refrigerated

70040 rev 1113-5

* http://www.gdx.net/tests/alphabetical#G

ASD CHILDRENIBS / IBD WEIGHT ISSUES

Asheville63 Zillicoa StreetAsheville, NC 28801

800 .522 .4762www .gdx .net

Atlanta3425 Corporate WayDuluth, GA 30096

800 .522 .4762www .gdx .net

LondonParkgate House356 West Barnes LaneNew Malden Surrey, KT3 6NB

020 .8336 .7750www .gdxuk .net

GI Effects - Interpretive Guide · Disease (IBD). Research has also noted associations with...

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