Presentation on theme: "The GI Tract – Clinical Insights from Stool, Urine and Blood"— Presentation transcript:
1 The GI Tract – Clinical Insights from Stool, Urine and Blood Presented by Terry Pollock, MSClinical EducatorNutrition Specialist
2 Big hello to all of the Nutrition Geeks folks! (The real me, at work last week…)
3 GI Health – What Is It? Absence of GI symptoms or illness Normal/stable intestinal microbiotaEffective digestion and absorption of foodsEffective immune statusDaily, “Type 4 or 5” bowel movements (TAP)General feeling of well-beingBischoff, S. Gut Health – a new objective in medicine? BMC Medicine 2011, 9:24IBDQ, BDQ, IBSQofLQ – “most suitable assessment tool”
4 GI Health – Two Major Determinants 1-The GI BarrierAllergic diseaseAutoimmune diseaseObesity, FLD/NASHSepsis – ICU ptsMalnutritionInfectious diarrheaIBDCeliac diseaseIBSBischoff, S. BMC 2011, 9:24
5 GI Health – Two Major Determinants 2 – GI MicrobiomeIBDCeliac diseaseIBSAllergyArthritisObesityBischoff, S. BMC 2011, 9:24
6 Testing the GI Barrier Lactulose/mannitol - urine Hydrogen breath testingIgG4 – serum or bloodspotHistology (villus, crypt, etc)LPS – cell membrane antigen in G-bacteriaLactoferrin - stoolImmunity – CBC, cytokines, sIgAWe will revisit some of these as we proceed
7 Testing the GI Microbiome Cell cultures, chemotaxis, phagocytosisBacterial/fungal cultures and toxins measurementsMetametrix:PCR – DNA-based identification/quantitationvia GIfx testMetabonomics – metabolites of gut bacteriavia Organix Dysbiosis testWe will go in depth in just a moment
8 It Is Usually Not One or the Other! The GI Barrier and the GI Microbiome Are Interrelated“significantly more variation in the gut microbiota of healthy volunteers than that of IBS patients”Codling C, et al, Dig Dis Sci, 2010 Feb;55(2):392
9 The GI Barrier and the GI Microbiome Are Interrelated HostpathologyAgeGenes, receptorsDiet ComponentsMode of birthNon-digestible CH2O, prebioticsGut MicrofloraMaternal floraGut mucosal pathology impacts gut flora, as recent research is indicating…Codling C et al, Dig Dis Sci 2010, p. 392 – IBS pts have less microbial diversity than healthy controls. Reason unclear…much more work needed.ProbioticsInfantenvironmentAntibiotics,drugs
10 Autoimmune Diseases Associated with Overgrowth of Specific Bacteria GI microbes linking to autoimmune pathology:Klebsiella: Ankylosing SpondylitisCitrobacter & Klebsiella: Rheumatoid ArthritisYersinia: Grave’s & Hashimoto’s Disease, Ulcerative ColitisAutoinflam, autoimmun dx associated with microbes
11 Irritable Bowel Syndrome (IBS) The disease entity “closest to the borderline between gut health and disease” - BischoffSymptoms – abdominal pain or tenderness, bloating, change in bowel habits; no other known organic causeRisk of developing IBS increases 6 fold after acute GI infection
12 Irritable Bowel Syndrome IBS-like symptoms are associated with three intestinal protozoan parasites:Blastocystis hominis – prevalence averages 30% in IBS patients. Prevalence in non-IBS patients ~7%Giardia lamblia – exposed group IBS 46% versuscontrols IBS 14% (Wensaas, Epub, Sept 2011)Dientamoeba fragilis – not as much dataavailableBlastocystis hominis
13 Irritable Bowel Syndrome IBS incidence in Chronic Fatigue Syndrome patients is 51%Psychiatric disorders are found in 94% of IBS patientsWhitehead WE et al, Gastroenterology 2002, p. 1140Probiotics (VSL #3, L. rhamnosus, B. breve) improve IBS flatulence, distension and painCollado MC et al. Current Drug Metabolism 2009, p 68
14 GI Health – What We Often See BloatingFlatulenceGERDNauseaVomitingHeartburnConstipationDiarrheaFood sensitivitiesIncontinenceAbdominal painLoss of appetiteWeight loss/gainBlood in stoolsDo not all originate in gut, but most seem to be remediated by optimizing gut function and support.May not all originate in gut, but seem to be remediated by optimizing gut function and support!
15 GI Barrier Disorders Overview Ulcerative Colitis, Crohn’s Selected TestsCase/TherapiesWe will talk about some GI barrier issues and see connections between microbes and these disease
16 The Importance of Mucosal Immunity “The dominating part of the immune defense, even if flora is excluded, is localized in the gut—no less than 75% of the immune cells of the body are suggested to be found in the GI tract.”So much is immune-related…makes sense barrier d/o’s would have large immune componentBengmark S. Acute and "chronic" phase reaction--a mother of disease, Clin Nutr, Vol. 23, No. 6, pp , December 2004
17 Autoimmune/leaky gut/Celiac connection Fasano A. Surprises from Celiac Disease. Scientific American, August 2009
18 Investigating the GI Barrier Lactulose/mannitol - urineHydrogen breath testingIgG4 – serum or bloodspotHistology (villus, crypt, etc)LPS – cell membrane antigen in Gram-bacteriaLactoferrin - stoolImmunity – CBC, cytokines, sIgA
19 Hyperpermeable GI Barrier 11 out of 30 foods cause rxn – so not only food sensitivities, but leaky gut
20 Hyperpermeable GI Barrier Lactulose/Mannitol Urine test for Leaky Gut – Lactulose molecule is larger and should not pass through to show up in urine. Mannitol should.Leaky Gut – both L and M are elevated in urineMalabsorption – both L and M are low in urine
21 Hyperpermeable GI Barrier “Since the mucosal immune system is a central component of host defense, as a whole, any dysregulation and inflammatory reaction in the GI tissue results in intestinal barrier dysfunction and the entry of undigested dietary proteins into the circulation….…The entry of dietary proteins in the circulation results in systemic immune response and the production of very high levels of IgG and IgA against dietary proteins and peptides. This systemic immune reaction against dietary proteins and peptides depends on the antigenic structure protein antigen, particulate antigens, polysaccharides, lipoproteins or enzymes and their molecular sizes, and of course, the genetic makeup of exposed individuals. One may produce IgG antibodies against dietary proteins, while others may produce IgA antibodies, or IgG and IgA antibodies against different dietary proteins and peptides.”Aristo Vojdani, PhD, immunologist, researcherItalics mine (TAP)
22 IBD - Ulcerative Colitis CharacteristicsAny part of colonDiarrhea ~4X/dMildly tender abdomenFatigueWeight loss if severe caseIncreased oxidative stressImpaired colonic mucosal barrier -lesions very permeableColon biopsy shows low copper/zinc
23 IBD - Ulcerative Colitis Helpful Tests and Potential FindingsGIfx stool analysis – H lactoferrin, H absorption markersFatty acids – H arachidonic acid? OR mostly low fatty acids?8OH-2DG, lipid peroxides – H in oxidative stressInflammation markers – H crp, fibrinogenLactulose/mannitol or IgG4 for permeabilityRBC elements – L zinc and copperSometimes lip perox is low – if fats are low in malabsorption especially
24 IBD - Crohn’s Disease Characteristics: Lower ileum usually, may occur at any locusDiarrhea ~4X/d (often twice as many)LRQ painBloody stoolFatigueWeight loss/anorexiaCrohn’s pt’s small bowel bact markers in case coming up
25 IBD - Crohn’s Disease Helpful Tests and Potential Findings GIfx stool analysis – H lactoferrin, malabsorptionOrganix Dysbiosis urine test – H bacterial markersFatty acids – all L/L normal - malabsorptionFat-soluble vitamins – most L8OH-2DG, lipid peroxides (oxid stress) - elevatedFerritin – low or sometimes very high!CBC – Low rbc’s, macrocytic cells, anemia
26 Russ - 48 yo m – Crohn’s History – Remicade Rx d/c– was not working 10 + bowel movements/dHypothryroidism - on thyroid medEndoscopy showed Crohn’s-like inflammationSeveral antibiotics courses earlier
27 Russ - 48 yo m – Crohn’s Labs - H lactoferrin, H calprotectin, H leukocytes (original testing)Candida albicans negFood sensitivities –IgG + buckwheatIgG4 mod/severe + to casein, milk
28 Russ - 48 yo m – Crohn’s disease Supplements:DGL capsL-glutamine powderOTC Probiotics
29 Russ - 48 yo m – Crohn’s Borderline low anaerobes across the board. Borderline low probiotics even though taking them.GIfx can show successful probiotics therapy
30 Russ - 48 yo m – Crohn’s“Low” total SCFA’s! Always look at number, not just at marker on the graph.Lactoferrin no longer H, but not where we see in non-IBD patients (1st Q), so pt is in remission or quiescence
32 Russ - 48 yo m – Crohn’sClear SIBO! Moral of story – stool samples can’t offer much about small bowel bacterial overgrowth!
33 Russ - 48 yo m – Crohn’sBacterial action on polyphenols, tyrosine, unabsorbed phenylalanineHPA – intestinal pathologyHippurate common in urine, but VH hippurate (from H bacterial benzoate) calls for more glycine to conjugate it in liver….Still no sign of Candida
34 Russ – Crohn’s – follow-up 4 months later follow-up:Mainly 3- 4 bm’s per day. Feels “not well, but much better”Added in interim:Red yeast rice, vit D, vit C, milk thistle,Vit E, zinc carnosine, professional probioticNeeds to support colonic bacteria:I further recommended Biotagen, Therbiotic Complete, curcumin, anti-infl diet changes, no dairy!
35 GI Microbiome Disorders OverviewTestingMicrobial Therapy
36 “It is today generally accepted that intestinal flora [are] deeply involved In the pathogenesis of human inflammatory bowel diseases (IBDs). Although the exact presence of unwanted or lack of specific crucial bacteria are not yet known. Westerners lack, to a large extent, important immunomodulatory and fibre-fermenting lactic acid bacteria (LAB), bacteria which are present in all with a more primitive rural lifestyle”.Bifidobacter in colonBengmark S. Bioecological control of inflammatory bowel disease.Clin Nutr, 26, 2007, p
37 Gut Microbiome Factoids There are ~1000 species of microbes in the human intestinal tract - totaling over 4 lbsThere are 10 times the number of microbial cells as human cells in the body (90% of DNA in our body is bacterial!!)Metabolic activity of our gut bugs rivals that of the liver
38 Colonization Resistance Normal GI microbiota:provides a natural defense mechanism against invading pathogensprevents overgrowth of opportunistic microorganismsprovides colonization resistance in a variety of ways, including:occupying adhesion sitesproducing antimicrobial agents
39 Testing the GI Microbiome Cell cultures, chemotaxis, phagocytosisBacterial/fungal cultures and toxins measurementsMetametrix:PCR – DNA-based identification/quantitationvia GIfx testMetabonomics – metabolites of gut bacteriavia Organix Dysbiosis test
40 Obese mice on the same diet as lean mice demonstrate higher increase in body fat, indicating the microbial community seems to affect the amount of energy extracted from the diet.Germ-free mice inoculated with microbiota from obese mice increased in adiposity over germ- free mice inoculated from lean mice while on the same diet.Ley R, Turnbaugh P, Klein S, Gordon J, Human Gut Microbes, Nature, V444, December 21/28, 2006
41 Mechanism of “Fat Bugs” Effect á CHO-Degrading EnzymesIncreased blood lipidsâ Fasting-Induced Adipose FactorIncreased adipocyte storageâ AMP-Activated Protein KinaseReduced energy for muscular activity
42 Sacchromyces boulardii as Therapy Antibiotic-Associated Diarrhea:N = 466 children, 1-15 yrs of ageAzithromycin alone 11.4% diarrhea+ S. boulardii 5.5% diarrheaSulfactam-ampicillin 25.6% diarrhea+ S. boulardii 5.7% diarrheaErdeve O, J Trop Pediatr 2004, p 234
43 Lactobacillus in Antibiotic-Associated Diarrhea 10 studies – total of 1862 patients, 6 studies were patients >18 yrs (a meta-analysis)Risk ratio of developing AAD was significantly lower when Lactobacillus was given, compared to placeboKale-Pradham PB. Pharmacotherapy, 2010, p. 119.
44 SHEILA - 33 yo f - constipation History:ConstipationBelching, gasMild depressionFatigueB12 deficientVitamin D deficientIron deficientOn GF diet for ~ 1 yearAntibiotics 2 months for tooth infection
45 SHEILA - 33 yr old femaleOn antibiotics 2 months earlier for tooth infectionLowest value is for Fusobacteria; this genus is often found in infections of mouth (abx tx?)
46 SHEILA - 33 yo fFungal overgrowths are common after antibiotic treatments+4 is our highest ratingObservation – anti-fungal botanicals usually bring TU fungi down
47 SHEILA - 33 yo fVERY LOW Short Chain Fatty Acids are consistent with constipation (and often diarrhea too).More about SCFA’s just upGF diets effectively lower AGA sIgA.
48 SHEILA – 33 yo f Trend persists: H nml trigs plus H nml Absorption markers – LCFA’s, Total fat and cholesterolThis trend correlates with gluten sensitivity
49 SHEILA – 33 yo f Treatments Suggested: Prebiotic supplements Anti-fungal dietSacchromyces boulardii mg/cap = 3 billion CFU’s - 1 bid with mealsIncrease water intakeFollow-up:Added psyllium on her own – after 5 weeks has better BM’s and less gas!
50 Short Chain Fatty Acids Derived from microbial fermentation of undigested carbohydrate (fiber) that reaches the colonAct as “physiological ligands” of FFA receptors 2 and 3, which are expressed in immune, endocrine and fat cells, to name a fewIncrease colonic and hepatic blood flowIncrease solubility of Ca++Increase absorption in the small intestine
51 Short Chain Fatty Acids Major SCFA’s studied are acetate, butyrate and propionateLow SCFA’s on stool testing mean more prebiotic soluble fiber is needed…and more bacteria to process them are needed also!Bacteroides species, etc can change SCFA profile (MacFarlane, 1996).Prebiotics can increase Bacteroides.
53 HENRY - 60 year old male, hx “chronic GI problems”, no GERD, big tummy (loves beer) Labs: (non-MMX)H serum anti-gliadin antibodiesSeveral other IgA-mediated markers H4 of 6 autoimmune markers positive(Cyrex Labs, Phoenix, AZ)Very new case I’ll follow
54 HENRY - 60 yo male Lower levels of predominant bacteria Higher Bifidobacter associated with less weight gain…
55 HENRY - 60 yo male, hx chronic GI problems No GERD, but is this level of Hp a problem?This +2 Sacch may be brewer’s yeastObservation – chronic Blastocystis is concurrent with IBS symptoms in some people
56 HENRY 60 yo male, hx chronic GI problems Nml lactoferrin,rather than >3rd Q, is a good finding!If lactoferrin H, IBD likelyWhen LOW sIgA, anti-gliadin sIgA may be ‘false negative’;H lactoferrin – can distinguish IBD from IBSHenry’s blood tests showed H AGA, so he has gluten sensitivity
57 HENRY - 60 yo m, hx chronic GI problems Digestion issues – H Putrefactive SCFA’s (protein)Malabsorption of LCFA’s (VH marker)Observation – pattern of H or H nml trigs with one or more Absorption markers H often is associated with gluten sensitivity. Persists long after GF diet is started.
58 HENRY - 60 yo m, hx chronic GI problems GF diet, learn to like GF beerDigestive enzymes with trial of HClPre- and probiotics dailyExperiment with new foods providing prebiotic substrate (replacing gluten foods)
59 General Gut-Healing “Go To’s” Biotagen – prebiotic powder containing inulin, oligofructose, beta-glucan and Larch arabinogalactanTher-Biotic Complete probiotic (7 Lactobacilli, 4 Bifidobacteria and Streptococcus thermophilus)Theralac (5 Lactobacilli with two prebiotics)Zinc carnosine – 50 mg bidL-glutamine – 1-35 g/dCurcumin – 50 mg (Meriva) 2-6/dDGL – mg/d powder
61 An Ecological Perspective The effects of the GI microflora are not mediated by a single species but rather by relationships among many. Therefore, characterization of the global composition is critical to understanding the effects of the microbiota on the host.From digestion, immune function to neurotransmitter production to correlation w/ certain diseases…. Listen to what the gut has to say…..
62 Intestinal Transit Time Many clinicians consider Types 4 and 5 to be in the “normal” or ideal range
63 GI Complications in Eating D/O Esophageal spasm/tearingGastric dilationAcute pancreatitisMotility issuesNutritional deficiencies – esp. Zn, Mg, B’s, EFA’s, calories, protein, vitamin KLow serotonin in bulimia/anorexia – available tryptophan prioritized to make vital protein!