2/28/2014

IBS: THE EVIDENCE FOR USE OF NUTRITION THERAPY

IBS: THE EVIDENCE FOR USE OF NUTRITION THERAPY

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IRRITABLE BOWEL SYNDROME 

AFFECTS 7-20% OF THE POPULATION   

CAPNI SPRING CONFERENCE MARCH 8, 2014 NANCY M. STRANGE, RD, CNSC, CLT [email protected]

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20-50% OF ALL REFERALS TO A GASTROINTESTINAL SPECIALIST

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NO PATHOGENIC DISEASE CAUSE FREQUENTLY ASSOCIATED WITH DEPRESSION AND/OR ANXIETY

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PREVIOUSLY THOUGHT TO BE PSYCHIATRIC 

NEED TO RULE OUT UC, CROHN’S, CARCINOMA, CELIAC DISEASE

INTESTINAL MUCOSA   

ECONOMIC BURDEN 

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PATHOPHYSIOLOGY OF IBS 

A DIAGNOSIS OF EXCLUSION 

ONLY 15- 25% SEEK MEDICAL HELP

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

IBS

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ESTIMATED ANNUAL COST IN UNITED STATES 

DIRECT: $1.7 TO $10 BILLION

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INDIRECT: $20 BILLION

DECREASE IN MALE USE OF HCS ?

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IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY

PRESENT IN ALL AGE GROUPS AFFECTS PEOPLE IN MANY DIFFERENT CULTURES FEMALE PREDOMINATE ~ 60- 65%

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OVER THE PAST 10 YEARS: 

QOL ISSUES SIGNIFICANT SECOND HIGHEST CAUSE OF WORK ABSENTEEISM

ENDOSCOPICALLY NORMAL HISTIOLOGICALLY NORMAL VISCERAL HYPERSENSITIVITY – FREQUENT FINDING SIGNIFICANT NUMBER OF INDIVIDUALS WITH IBS ALSO HAVE AN ABUSE HISTORY

DYSREGULATON OF THE BRAIN-GUT AXIS 

POTENTIAL ALTERATIONS AT DIFFERENT LEVELS ENTERIC AUTONOMIC AND/OR CNS DISTURBED INTERPLAY BETWEEN THESE SYSTEMS   

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

TREATMENT MODALITIES AND OUTCOMES 

ANTISPASMODICS/BULKING AGENTS 

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MINIMAL IMPROVEMENT IN SYMPTOMS

5HT4 AND 5HT3 ANTAGONISTS 

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10% IMPROVEMENT IN TREATMENT GROUP VS PLACEBO GROUP SEVERE SIDE EFFECTS  

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IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

“NOVEL” TREATMENT 

CASE REPORTS OF IMPROVEMENTS WITH PROBIOTIC USE 

STIMULATED RESEARCH

CARDIOVASCULAR RISKS ISCHEMIC COLITIS

PREDNISONE   

NO CHANGES IN INFLAMMATORY MARKERS WITH IBS NO IMPROVEMENT IN SUBJECTIVE SYMPTOMS SEVERE NUTRIENT COSTS

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IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

IBS 

RESEARCH HAS FOUND:       

ALTERATIONS IN FECAL FLORA ELEVATED INTESTINAL PERMEABILITY BACTERIAL OVERGROWTH FOOD SENSITIVITY ACTIVATED T LYMPHOCYTES INCREASED MAST CELLS MEDIATORS KNOWN TO SIGNAL EPITHELIAL, NEURONAL AND MUSCLE CELLS

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY  

PHYLOGENETIC ABUNDANCE WITHOUT IBS/DISEASE

ALTERATIONS IN FECAL FLORA Malinen

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

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Lower amounts of Lactobacillus species in IBS-D  Increased amounts of veillonella species in IBS-C  Clostridium coccoides and bifidobacterium differences between IBS and normal controls 

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Molecular analysis Significant difference in flora from controls 2 fold increased ratio of the Firmicutes to Bacteroidetes (1.5 fold increase in the numbers of Dorea, Ruminococcus and Clostridium spp.) 2 fold decrease in bacteroidetes 1.5 fold decrease in bifidobaterium and faecalibacterium spp 

AM J Gastroenterol. 2005;100(2):373

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

Rajilic-Stojanovic

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IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

Jeffery Clustering by microbiota composition  Revealed sub group classifications within the IBS patients 

1. Normal microbiota contents  2. Increase in Firmicutes  3. Depletion of Bacteroides 

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Jeffery IB, O’Toole PW, et al, GUT 2012 Jul;61(7)

Gastroenerology 2011;141(5): 1792

INCREASED INTESTINAL PERMEABILITY 

DOCUMENTED IN 12-50% OF INDIVIDUALS WITH IBS 

IMPROVEMENTS IN PERMEABILITY AND IBS SYMPTOMS WITH:    

STREPTOCOCCUS THERMOPHILUS LACTOBACILLUS BULAGARIS LACTOBACILLUS ACIDOPHILUS BIFIDOBACTERIUM LONGUM CARRIER: FERMENTED MILK ALIMENT PHARMACOL THER 2008 

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IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

BACTERIAL OVERGROWTH FOUND TO BE PRESENT IN ~ 4% OF IBS POPULATIONS  ?? TREATMENTS WITH RIFAXAMIN 

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IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY SPECIFIC FOODS

FOOD SENSITIVITY    

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WOULD YOU RECULTURE?

INCREASED IgA LEVELS INCREASED CYTOKINE PRESENCE WHICH CAME FIRST? IBS OR FOOD SENSITIVITY?

FOOD ALLERGIES   

IgG MEDIATED IgE MEDIATED IMMUNE RESPONSES DO NOT CORRELATE WITH IBS GI SYMPTOMS NO EVIDENCE THAT IBS IS CAUSED BY FOOD ALLERGIES

UNDIGESTED RESIDUES

COLONIC FERMENTATION

NORMAL GUT FLORA

ABNORMAL GUT FLORA

TOXIC METABOLITE

NON TOXIC METABOLITES DESTROYED BY HOST ENZYMES

NOT DESTROYED

NO SYMPTOMS IBS

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY

Mast Cell Infiltration in IBS

ACTIVATED IMMUNE SYSTEM MAST CELL CONCENTRATION SIGNIFICANTLY HIGHER DENSITIES IN IBS VS CONTROLS INCREASED PAIN WITH INCREASED MAST CELL PRESENCE

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IBS:CHANGES IN TLR IN 3 TYPES OF IBS

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

ALTERATIONS IN 

TLR4 AND TLR5 – INCREASED IN IBS VS NORMAL CONTROLS

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INCREASED ANTIBODIES TO BACTERIAL FLAGELLIN AND B-DEFENSIN 2 LEVELS

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COLONIC MUCOSA

IBS: IL8, IL1BETA, IL6, TNFa LEVELS

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

ALTERATION IN IL 10 AND IL 12 LEVELS 

WITH ABNORMAL FLORA IN IBS 

IL 10 LEVELS LOWER IN IBS PATIENTS 

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IL 10 DEACTIVATES MACROPHAGES WHICH IN TURN DECREASE PRODUCTION OF CYTOKINES BY T CELLS IL 10 PROMOTES Th2 CELL DOMINANCE 

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

IL 12 PROMOTES Th1 RESPONSES  INCREASES INFLAMMATION  INCREASED IL 12 WITH ALTERED MICROBIOME OR INTESTINAL PERMEABILITY

UP TO DATE 2013: ROLE OF CYTOKINES IN THE IMMUNE SYSTEM

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

CYTOKINES 

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IL8 - >ALL TYPES OF IBS 

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IL 1B - >ALL TYPES OF IBS   

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INCREASES HISTAMINE RELEASE, RESPIRATORY BURST; INDUCES CHEMOTAXIS AND PHAGOCYTOSIS MEDIATOR OF INFLAMMATORY RESPONSE PRODUCED BY ACTIVATED MACROPHAGES INDUCES CYCLOXYGENASE2 IN CNS, INCREASES INFLAMATORY PAIN HYPERSENSITIVITY

IL 6 > IBS-D, IBS-M  

SECRETED BY MACROPHAGES MEDIATOR OF THE ACUTE PHASE RESPONSE TYPES

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IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

TNFalpha - > IBS-M   

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IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY

INVOLVED IN SYSTEMIC INFLAMMATION STIMUALTES ACUTE PHASE RXN PRODUCED BY ACTIVATED MACROPHAGES

IFNy (INTERFERON GAMMA) - < ALL TYPES  

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CAUSES INCREASE IN Th0 DIFFERENTIATION TO Th1 CELLS CRITICAL FOR INNATE AND ADAPTIVE IMMUNITY AGAINST VIRAL AND IC BACTERIAL INFECTIONS SECRETED BY Th1 CELLS SUPPRESSES Th2 CELL DIFFERENTIATION

QUESTIONS

QUESTIONS  

WHAT ROLE DOES VITAMIN A HAVE IN THE INTEGRITY OF THE ENTERIC EPITHELIUM?

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RETINOIC ACID REGULATES TGF-BETA IMMUNE RESPONSES.  WITHOUT RETINOIC ACID AND IN THE PRESENCE OF IL-6, TGF-BETA PROMOTES THE DIFFERENTIATION OF NAÏVE T LYMPHOCYTES INTO IL-17 WHICH PROMOTES AUTOIMMUNITY AND INFLAMMATION.

ARE NON RESPONDERS TO PROBIOTICS DIFFICIENT IN MICRONUTRIENTS REQUIRED FOR COMMENSUAL AND HUMAN HEALTH? 

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

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MAGNESIUM, B COMPLEX, VITAMIN A, VITAMIN C

HOW IS THE IMMUNE ACTIVIATION AFFECTED BY PROTEIN AND OR MICRONUTRIENT DEPLETION?

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY

O’MAHONEY RESEARCH 

BIFIDOBACTERIUM INFANTIS    

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LACTOBACILLUS SALIVARIUS   

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CYTOKINE LEVELS RETURNED TO LEVELS SIMILAR TO THOSE OBSERVED IN THE HEALTHY CONTROL GROUP DECREASE IN ABDOMINAL PAIN DECREASE IN BLOATING DECREASE IN BOWEL MOVEMENT DIFFICULTY

CYTOKINE LEVELS DID NOT CHANGE DECREASE IN ABDOMINAL PAIN, TEMPORARY SMALL CHANGE IN BLOATING

SMALL STUDY SINGLE USE PROBIOTIC SMALL PLACEBO EFFECT IN CONTROL GROUP

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IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

ENTERIC NERVOUS SYSTEM 

VISCERAL HYPERSENSITIVITY   

INCREASED IN IBS LACTOBACILLUS ACIDOPHILUS INCREASES EXPRESSION OF ENTEROCYTE OPIOID AND CANNABINOID RECEPTORS  

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY EFFICACY OF PROBIOTICS IN THE TREATMENT OF IBS  MOAYYEDI, 2008 

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19 RCTs 

INHIBITS SODIUM CHANNELS REDUCES VISCERAL HYPERSENSITIVITY (PAIN)

Forest plot of trials  

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LACTOBACILLUS RHAMNOSUS GG 

REDUCED ACETYLCHOLINE STIMUALTED COLONIC CONTRACTIONS HUMAN STUDY DOSE AND TIME DEPENDANT

OUTCOME:  

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IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY

Dichotomous outcome Continuous outcome

SMALL STUDIES DIFFICULT TO ASSESS EFFICACY DUE TO MULTIPLE TYPES OF PROBIOTICS USED TREND OVERALL FAVORS USE OF PROBIOTICS

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

PROBIOTIC STRAIN/EVIDENCE GRADE 

BIFIDOBACTERIUM INFANTIS

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BIFIDOBACETIUM ANIMALIS

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B – ABD PAIN/BLOATING 

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BIFANTIS (BRAND)

B – ABD PAIN C – IBS- CONSTIPATION TYPE ACTIVIA (BRAND)

LACTOBACILLUS CASEI SHIROTA  

B – ABD PAIN C – CONSTIPATION 

YAKULT (BRAND)

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LEVELS OF EVIDENCE: A – RANDOMIZED CONTROLLED CLINICAL TRIAL, COHORT STUDY B – RETROSPECTIVE COHORT, EXPLORATORY COHORT, ECOLOGICAL STUDY, OUTCOMES RESEARCH, CASE-CONTROL STUDY, EXTRAPOLATIONS FROM LEVEL A STUDIES C – CASE SERIES STUDY OR EXTRAPOLATIONS FROM LEVEL B STUDIES  

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IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY 

LACTOBACILLUS PLANTARUM

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LACTOBACILLUS RHAMNOUS

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ESCHERICHIA COLI NISSLE

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C – ABD PAIN

B – IBS PAIN 

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CULTURELLE; LGG; GEFILUS

C – IBS CONSTIPATION MUTAFLOR

COMBINATION PREPARATION 

C – IBS PAIN 

VSL#3

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LEVELS OF EVIDENCE: A – RANDOMIZED CONTROLLED CLINICAL TRIAL, COHORT STUDY B – RETROSPECTIVE COHORT, EXPLORATORY COHORT, ECOLOGICAL STUDY, OUTCOMES RESEARCH, CASE-CONTROL STUDY, EXTRAPOLATIONS FROM LEVEL A STUDIES C – CASE SERIES STUDY OR EXTRAPOLATIONS FROM LEVEL B STUDIES

IBS: THE EVIDENCE FOR USE OF PROBIOTIC THERAPY FOOD SOURCES OF PROBIOTICS YOGURT – ACTIVE CULTURE KEFER FERMENTED FOODS SAUERKRAUT, PICKLES, SUMMER SAUSAGE CULTURED DAIRY PRODUCTS MISO TEMPEH OTHERS?

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IBS AND NUTRITION THERAPY

NUTRITION THERAPY 

RESEARCH IS ONGOING FOR PROBIOTIC USE

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FIBER AND IBS 

DEFINING NORMAL  DEFINING WHICH STRAINS HAVE WHICH FUNCTIONS  DEFINING CULTURAL DIFFERENCES 

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IBS AND NUTRITION THERAPY 

FODMAP DIET 

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FODMAPS: FERMENTABLE OLIGO  DI MONO- SACCHARIDES  AND  POLYOLS 

Clinical Gastroenterology and Hepatology 2008;6:765-771 

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Double blinded, randomized, quadruple arm, placebocontrolled rechallenge trial Diet low in short chained CHO 70-79% improvement in IBS symptoms Improvement sustained with diet changes 

FODMAP DIET 

ALL ARE CARBOHYDRATES LACTOSE  FRUCTOSE  FRUCTANS  POLYOLS  GALACTANS

NO IMPROVEMENT INCREASED BLOATING/PAIN

FODMAP DIET

Susan Shepherd et al 

VERY POOR RESPONSE TO INCREASING FIBER

FODMAP DIET 

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LACTOSE (DISACCHARIDE)  

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LACTOSE CONTAINING DAIRY MEDICATIONS/SUPPLEMENTS

FRUCTOSE (MONOSACCHARIDE)  

FRUIT, JUICES, HFCS MAXIMUM ABSORPTION 5-50 GMS/DAY

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FODMAP DIET FRUCTANS (OLIGOSACCHARIDES)  WHEAT, RYE, BARLEY, CHICORY ROOT, INULIN, ONIONS, SCALLIONS, GARLIC, SHALLOTS, RADICCHIO, BRUSSEL SPROUTS, CABBAGE, BEETS, BANANAS  POLYOLS (SUGAR ALCOHOLS)  SORBITOL, MANNITOL, XYLITOL, ISOMALT  CHERRIES, PLUMS, PRUNES, AVOCADO, MUSHROOMS, CAULIFLOWER  SIBO SEEMS TO INCREASE SENSITIVITY TO POLYOLS  GALACTANS (OLIGOSACCHARIDES)  DRIED PEAS AND BEANS, NUTS AND SEEDS 

FODMAP DIET 

EFFECTS ARE ADDITIVE  

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NOT FOOD ALLERGIES 

CONCEPT BEHIND THE DIET

FODMAP DIET 

Symptoms are triggered by the ingestion of FODMAP foods in sensitive individuals due to enteric nervous system to luminal distension  Not considered malabsorption/maldigestion  Underlying bowel response is exaggerated or abnormal

Three common characteristics: Poorly absorbed Rapidly fermentable  Osmotically active molecules

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FODMAP DIET 

GOAL OF DIET Assess tolerance to a type of CHO  Limit IBS symptoms  Provide the most variety of foods in diet  Diet does not address chemical sensitivities 

NOT IgG DRIVEN

FODMAP ISSUES CAN BE ALSO PRESENT IN IBD  ARE NOT THE CAUSE OF THE UNDERLYING FGID  PRESENCE OF FODMAPS IN DIET IS “NORMAL”  INDIVIDUAL RESPONSE TO FODMAPS IS ALTERED. 

FODMAP 

CAN TOLERATE LOW LEVELS OF FODMAP FOODS SYMPTOMS CAN WORSEN WITH “IMPROVEMENT” IN DIET CHOICES

FODMAP DIET 

BEST CANDIDATES FOR DIET IBS D, C, M, IBD Failure to respond to standard, high fiber diet  Celiac disease ruled out  Willing and able to adhere to nutrition therapy  Current diet is high in FODMAPs  

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FODMAP DIET

FODMAP DIET 

NOT CANDIDATES FOR DIET: No control over food preparation/purchasing Inflexible food preferences Underweight, medically fragile patients Eating disordered patients only with a risk vs benefit evaluated carefully

Phase 1 Elimination of all FODMAP foods  No probiotics, unless already taking  Limit seasoning to approved list only  No caffiene 

FODMAP DIET 

Phase 2 

FODMAP DIET 

Challenge phase – once symptoms are significantly improved only

VALIDATION OF FODMAPS WITHIN FOODS  GMO FOOD EVALUATIONS 

Re-introduce FODMAP foods one group at a time  Continue to eliminate all other groups except the challenge group  Allow 3 days for symptoms to recur  Phase 2 is meant to cause symptoms to recur. 

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LEAP 

Life Style Eating and Performance Performed by an advanced practice RD  Involves evaluation of food and chemical sensitivities via MRT  3-4 months of individualized lifestyle/diet counseling  Incorporates guidelines for healthy eating

RESEARCH NEEDED

FODMAPS NUTRIENTS

LEAP 

Medical conditions where food sensitivities can play a primary or secondary role:

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IBS CROHN’S/UC GERD MIGRAINES, NOT WEATHER RELATED FIBROMYALGIA, CFS DEPRESSION, ANXIETY METABOLIC SYNDROME, OBESITY

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LEAP: FOOD SENSITIVITIES 

FOOD SENSITIVITIES

FOOD SENSITIVITIES 

ANY inflammation generating reaction against a specific food or food component that does not involve type 1 IgE-medicated food allergy.

Sensitivity 94.5% Specificity 91.7%  Split Sample Reproducibility >90%  

LEAP 

FOOD SENSITIVITIES

Uses Mediator Release Testing (MRT) Functional measure of sensitivity based inflammatory responses  Measures WBC reactions to a food/chemical  Quantifies the degree of inflammatory response.  Tests 150 compounds  Blood test 

FOOD SENSITIVITIES 

GLUTEN SENSITIVITY  

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NON CELIAC GOVERNED BY INNATE IMMUNITY  FIRST TIME INNATE IMMUNE SYSTEM IDENTIFIED IN FOOD ISSUES GUT PERMEABILITY LESS THAN CELIAC LOW TO MODERATE INFLAMMATION PRESENT NO VISIBLE TISSUE DAMAGE

GLUTEN SENSITIVITY 

PRESENTING SYMPTOMS Brain fog Joint pain  Muscle pain  Headaches  Diarrhea  

Fasano et al. BMC Med 2011

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GLUTEN SENSITIVITY

NUTRITION THERAPY AND LEAP ELIMINATION DIET BASED ON MRT RESULTS ELIMINATES FOOD FAMILIES

ESTIMATES OF PREVALENCE 15-20 MILLION AMERICANS 6-8 TIMES THE INCIDENCE OF CELIAC DISEASE

GUIDES A REINTRODUCTION DIET SYMPTOM SURVEY THROUGHOUT THE PROCESS

NUTRITION THERAPY AND LEAP TESTING ORDERED BY PHYSICIAN  IMPLEMENTATION BY A CERTIFIED LEAP THERAPIST 

USUALLY AN ADVANCED PRACTICE REGISTERED DIETITIAN  CERTIFICATION AND MENTORING PROGRAM REQUIRED.

IBS AND NUTRITION THERAPY 

RESEARCH IS RETURNING US TO DIET THERAPY 

ADVANCED LEVEL OF NUTRITION THERAPY

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ADVANCED LEVEL OF KNOWLEDGE REQUIRED  IMMUNE SYSTEM  INTEGRATION OF MICROBIOME RESEARCH OUTCOMES ARE SIGNIFICANT  IMPROVEMENTS IN 50-79% OF PATIENTS WITH CHRONIC ISSUES

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IBS AND NUTRITION THERAPY

QUESTIONS?

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