Stool Testing Support Guide - Genova Diagnostics

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Stool Testing Support Guide

Genova Diagnostics Stool Support GuideTable of ContentsIntroduction. 3Biomarker Comparison Charts. 4-5GI Effects Results Overview. 6Functional Imbalance Scores. 7Therapeutic Support Options. 7GI Effects Commensal Microbiome Analysis. 8Commensal Abundance. 8Total Commensal Abundance. 8Relative Commensal Abundance. 8Commensal Dysbiosis Patterns. 9Inflammation-Associated Dysbiosis (IAD) Score. 9Methane Score. 9Dysbiosis Zones Graphic. 9Commensal Balance.10Reference Variance Score.10Healthy-Pattern Continuum.10Digestion and Absorption.11Pancreatic Elastase 1. 11-12Products of Protein Breakdown (Putrefactive Short Chain Fatty Acids).13Fecal Fats. 14-15Chymotrypsin.15Meat and Vegetable Fibers.16Inflammation and Immunology.17Calprotectin.17Eosinophil Protein X.18Fecal secretory IgA.19Fecal Lactoferrin.20Gastrointestinal Microbiome.21Metabolic Indicators.22Short chain fatty acids. 22-23Beta-glucuronidase.24pH.25Secondary Bile Acids.26Commensal Bacteria.27PCR Commensal Bacteria. 28-29Firmicutes/Bacteroidetes Ratio.30Dysbiosis.30Clinical Associations Charts. 31-32Bacteriology and Mycology.33Bacteriology and Mycology Culture.33Bacteriology and Mycology Sensitivities. 34-35Potassium Hydroxide (KOH) Prep for Yeast.35Pathogenic Bacteria Enzyme Immunoassay (EIA) (Add-on only).36Parasitology.37Microscopic ova and parasites (O&P). 37-38PCR Parasitology - Protozoa.39EIA Parasitology.40Macroscopic Exam for Worms.40Therapeutic Considerations for Parasitology. 40-41Reflex Blastocystis subtyping 1-9. 41-44Additional tests.45Occult Blood.45Zonulin Family Peptide (Add-on only).45References. NDANCEGASTROINTESTINALMICROBIOMEFECALLACTOFERRIN2

INTRODUC TIONAdvances in research, combined with clinical insight, confirm the essentialrole of the gut in determining overall health and wellness. Genova’s stoolprofiles offer a comprehensive evaluation of GI function paired with thebroadest clinical utility available. It is important that clinicians possess thesetools since they provide the most accurate and comprehensive assessment ofgastrointestinal health.Genova’s line of stool testing provides immediate actionable clinicalinformation for gastrointestinal health management. Utilizing both advancedtechnologies and premier biomarkers, the GI Effects Stool Profiles andCDSA/CDSA 2.0 Profiles offer valuable insight into digestive function,intestinal inflammation, as well as the gastrointestinal microbiota. Our testsare designed to identify potential root causes of symptoms. They assistclinicians by providing targeted therapeutics that improve symptoms andoverall gut health.In addition to providing a comprehensive set of GI functional biomarkers,our stool profiles incorporate the most sophisticated tools in evaluating themicrobial community of the GI tract, known as the microbiota. Genova usesmultiple methodologies to provide the most clinically accurate assessmentof bacteria, yeast, and parasites currently available on the market. The GIEffects Profiles include quantitative assessment of commensal bacteriato determine healthy bacterial balance based on research and analysis ofhundreds of thousands of patient results. This data-driven, evidence-basedanalysis establishes a firm foundation from which to base clinical decisionsand treatment.Lastly, the GI Effects utilizes an innovative scoring system that synthesizes thebiomarker findings and groups them into 5 key areas relating to GI function:maldigestion, inflammation, dysbiosis, metabolite imbalance, andinfection. This allows for clearer visualization of patterns among biomarkers.Protocol design and management of abnormal GI function through dietary,lifestyle, nutraceutical, and other relevant interventions are thus enhanced.3

Gut Pathogen ProfileGI Effects Biomarkers Comparison Table2200*2205*2207**Not Available in New YorkDigestion and AbsorptionPancreatic Elastase-1 Products of Protein Breakdown (Total) (Valerate Isobutyrate Isovalerate) Fecal Fat (Total)TriglyceridesLong Chain Fatty AcidsCholesterolPhospholipids Inflammation and ImmunologyCalprotectinEosinophil Protein X (EPX)Fecal sIgA MetabolicSCFA (Total) (Acetate, n-Butyrate, Propionate)n-Butyrate Concentrationn-Butyrate %Acetate %Propionate %Beta- glucuronidase Gastrointestinal MicrobiomeCommensal Bacteria (PCR)Bacteroides-Prevotella groupBacteroides vulgatusBarnesiella spp.Odoribacter spp.Prevotella spp.Firmicutes PhylumAnaerotruncus colihominisButyrivibrio crossotusClostridium spp.Coprococcus eutactusFaecalibacterium prausnitziiLactobacillus spp.Pseudoflavonifractor spp.Roseburia spp.Ruminococcus spp.Veillonella spp.Actinobacteria PhylumBifidobacterium spp.Bifidobacterium longumCollinsella aerofaciensProteobacteria PhylumDesulfovibrio pigerEscherichia coliOxalobacter formigenesEuryarchaeota PhylumMethanobrevibacter smithiiFusobacteria PhylumFusobacterium spp.Verrucomicrobia PhylumAkkermansia muciniphilaFirmicutes/Bacteroidetes (F/B Ratio)BacteriologyMycology (Yeast/Fungi)ParasitologyMicroscopic Exam ResultsParasitology PCR TestsOther BiomarkersFecal Occult BloodColorConsistencyMic Sensitivities, Yeast or Bacteria Add-ons2203 Clostridium difficile EIA2204 Shiga toxin E. coli EIA2202 Campylobacter spp. EIA2206 Fecal Lactoferrin2208 Helicobacter pylori EIA2331 Macro Exam for Worms2336 Zonulin Family Peptide2338 KOH Preparation for Yeast 4

CDSA Biomarkers Comparison TableCDSACDSA/PCDSA 2.0/PCDSA 2.0 w/o P *Not Available in New YorkDigestion and AbsorptionPancreatic Elastase-1 Putrefactive SCFAs ChymotrypsinFecal FatsMeat FibersVegetable FIbers Gut ImmunologyFecal LactoferrinCalprotectinEsosinophil Protein XZonulin Family PeptideMetabolic MarkersBeneficial SCFAsSCFA DistributionBeta-glucuronidasepHn-Butyrate Lithocholic acid (LCA)Deoxycholic Acid (DCA)LCA/DCA Ratio Microbiology MarkersBacteriologyMycologyCampylobacter EIAShiga-like Toxin E.coli EIAClostridium difficile EIAHpSA-H. pylori EIAParasitologyMicroscopic O&PEIAMacroscopic Exam for Worms5

GI EFFEC TS RESULTS OVERVIEWThe GI Effects Stool Profile report is organized to providea quick overview and synthesis of results at the beginningof the test. The results overview graphic reflects the statusof the 3 key functions of gut health arranged in the “DIG”format: digestion, inflammation, and the gut microbiome.The gut microbiome section is further broken down intothree components: infection, metabolite imbalance, anddysbiosis. These individual gut microbiome sections allowthe practitioner to differentiate between interventionsthat are antimicrobial versus supportive of themicrobiome. The colorimetric circles reflect the need forsupport in each area and help the practitioner prioritizetherapeutic strategies. Green represents low need forsupport, gray (optional), yellow (moderate), and red (highneed).6

Functional Imbalance ScoresThe functional imbalance scores are generated usingweighted algorithms that incorporate biomarkersbelonging to each functional category. The biomarkersthat are represented in the algorithm are listed below thescore in each functional column. A qualitative indicatorof whether the biomarker is normal (green circle ) orabnormal (yellow or red arrow ) is located adjacentto the biomarker name. The level of need for support ina functional area is reflected both by the color and scorein the circle. Green represents a low need for support andcorresponds with scores less than 2, grey represents anoptional need for support and corresponds with a score of2 or 3, yellow indicates moderate need with scores of 4-6,and red indicates high need with scores of 7-10.Therapeutic Support OptionsTherapeutic support options are listed at the bottomtherapeutics for individual patients. More information onof each column. Therapeutic support options are statictherapeutic support options are discussed throughouton every report to serve as potential treatment ideas.this guide as they relate to each biomarker.Clinician discretion is advised when selecting appropriate7

GI EFFECTS COMMENSALMICROBIOME ANALYSISThe GI Effects features a synthesis of the patient’smicrobiome data. In addition to listing amounts of the24 commensal bacteria, Genova has developed uniquealgorithms that account for the levels of bacteria andtranslate the patient’s microbiome data into clinicallyactionable information. The commensal microbiomeanalysis focuses in the areas of abundance, dysbiosis, andbalance.Commensal AbundanceTotal Commensal AbundanceThe total commensal abundance is a sum-total of thereported commensal bacteria compared to a healthyand Sreportedcohort. Results are denoted with circle Patient:AMPLETIENTas a percent variance from healthy cohort levels.P ALowDOB:levels of commensal bacteria are often observedafterSex:antimicrobial therapy, or in diets lacking fiber and/Corporate Wayor3425prebiotic-richfoods and may indicate the need forDuluth, GA 30096microbiome support. Conversely, higher total commensalabundance may indicate potential bacterial overgrowth orprobiotic supplementation.MRN:2200 GI Effects Comprehensive Profile - StoolInterpretation At-a-GlanceINFECTIONDientamoeba fragilisBlastocystis spp.INFLAMMATIONCalprotectinEPX INSUFFICIENCYPancreatic Elastase 1 IMBALANCEBeneficial BacteriaPP Yeast/Fungi Relative Commensal AbundanceThe relative abundance compares the quantity of each of 7 major bacterial phyla to a healthy cohort. Phyla arerepresented by various colors and each is reported as a percent variance from healthy cohort levels. This can indicatebroader variances in the patient’s gut microbiome profile. Certain interventions may promote or limit individual phylawhen clinically appropriate.See individual sections for detailed resultsRELATIVE ABUNDANCEVerrucomicrobia PhylumFusobacteria PhylumEuryarchaeota PhylumProteobacteria Phylum*A progressive ranking scale based on a Genova proprietary algorithm that differentiates healthy and unhealthycommensal patterns.**The total number of Commensal Bacteria (PCR) that are out of reference ranges for this individual.PATIENT HEALTHYRESULTS COHORT Genova Diagnostics · Robert M. David, PhD, Lab Director · CLIA Lic. #11D0255349 · Medicare Lic. #34-8475 · Georgia Lab Lic. Code #067-007New York Clinical Lab PFI #4578 · Florida Clinical Lab Lic. #800008124Actinobacteria PhylumFirmicutes PhylumBacteroidetes Phylum2200B8

Commensal Dysbiosis PatternsGenova’s data analysis has led to the development of unique dysbiosis patterns, related to key physiologic disruptions,such as immunosuppression and inflammation. These patterns are based on the commensal bacteria and mayrepresent dysbiotic changes that could pose clinical significance.Inflammation-Associated Dysbiosis (IAD) ScoreThe Inflammation-Associated Dysbiosis score wasdeveloped from a pattern-based algorithm. Whengrouping patients according to their IAD scores, thegroup mean IAD score was negatively associated withcommensal abundance and positively associated withfecal calprotectin, EPX, and sIgA. The score was validatedin clinical studies including Genova’s database of IBDpatients, and an independent UCLA study with a cohortof IBD patients.1 More information about the IAD scorecan be found in the publication: 19-05828-8It is unknown whether inflammation-associated dysbiosisis a cause and/or an effect of inflammation. A low IADscore with elevated inflammatory markers indicates thegut microbiome may not play a role in the inflammatorycondition and other etiologies should be investigated (seezone 1 pattern description below). Longitudinal studiesare needed to determine the significance of a high IADscore with normal inflammatory markers. It is possible thatan inflammatory microbiome pattern may precede therise of inflammatory markers.Methane Dysbiosis Score (Immune Suppression)The Methane Dysbiosis score was derived from ananalysis of breath methane test results that correlatedwith certain markers on the GI Effects stool test. Genova’sunpublished data found a unique correlation withmarkers indicating immune suppression (low fecal sIgAand EPX) and the presence of methanogens, potentiallypathogenic bacteria, bacterial overgrowth, and certainparasitic organisms. (See zones 2 and 3 below for moreinformation.) This dysbiosis pattern is associated withimmune suppression and is distinct from the IAD pattern.It is unknown whether methane/methanogenic organismsare a cause and/or an effect of immune suppression. Anelevated methane dysbiosis score may warrant treatingpotentially pathogenic organisms depending on theclinical picture. Additionally, intestinal barrier therapiesmay be helpful in supporting intestinal immune function.Dysbiosis Pattern ZonesThe IAD and methane scores are placed on the x- and y-axis, respectively,and certain cut points create 4 distinct zones. Each zone is associated withdifferent clinical associations and treatment considerations.Zone 1: The commensal profile in this zone does not align with profilesassociated with intestinal inflammation or immunosuppression. Clinically,if a patient in this zone has elevated inflammatory biomarkers, othercauses of intestinal inflammation other than dysbiosis need to beexcluded. Other causes include infectious pathogens, celiac disease, foodallergies and sensitivities, or more serious pathologies.9

Zone 2: Profiles that demonstrate this pattern of bacteriaare associated with a suppressed innate immune system(low fecal sIgA and EPX) and potentially impairedintestinal barrier function. Patients in this zone statisticallyhave higher rates of opportunistic infections (e.g.Blastocystis spp. & Dientamoeba fragilis) as well as fecalfat malabsorption. In general, commensal abundanceis high in this group suggesting potential bacterialovergrowth. Treating potentially pathogenic organismsand microbiome modulation is suggested to reducemethanogens and improve gut-barrier function.Zone 3: A small fraction of patients are found with thispattern of commensal bacteria. Patients in this zone mayhave more inflammation compared to those in zone 4.However, commensal abundance is usually higher makinguse of antimicrobial therapy relatively safer. Patients in thiszone may have higher rates of pathogenic infections.Zone 4: The commensal profile in this zone is associatedwith increased intestinal inflammation. Patients withIBD are more

tools since they provide the most accurate and comprehensive assessment of gastrointestinal health. Genova’s line of stool testing provides immediate actionable clinical information for gastrointestinal health manag

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