DrDr‘RAJA’ ‘RAJA’ MANDYAM MANDYAM TirumalacharTirumalachar

Gastrointestinal DisordersGastrointestinal Disorders

Obesity + associated disordersObesity + associated disorders

Celiac DisordersCeliac Disorders

Irritable Bowel SyndromeIrritable Bowel Syndrome

MICROBIOTA of the MICROBIOTA of the Gut Gut

are the bacteria are the bacteria in part to in part to blame for:blame for:

? Microbiota

• refers to microflora and microfauna as a group; especially to the various bacteria that live in the gut of normal, healthy humans and other animals.

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Human Microbiota:Human Gut Bacterial Colonies

• Human body is made of 10 Trillion cells• Human gut houses

100 trillion bacterial colony made of 500-1000 different species• A great ECO system

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Relative Bacterial Concentrations and pH of the gut

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Name of PhylumName of Phylum Number of Number of SpeciesSpecies

Number of Number of GeneraGenera

AquificaeAquificae

XenobacteriaXenobacteria

ChrysogenetesChrysogenetes

ThermomicrobiaThermomicrobia

CyanobacteriaCyanobacteria

ChlorobiaChlorobia

ProteobacteriaProteobacteria

##FirmicutesFirmicutes

Planctomycetes etc.Planctomycetes etc.

SpirochaetesSpirochaetes

FibrobacterFibrobacter

##BacteroidetesBacteroidetes

FlavobacteriaFlavobacteria

2727

2929

11

1313

7878

1717

16441644

24742474

1313

9292

55

130130

7272

1212

1111

11

66

6262

66

366366

255255

55

1313

33

2020

15156

Bacterial flora and fauna of Bacterial flora and fauna of human guthuman gut

Bacterial Ratio:Fermicutes : Bacteriodetes

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Of Mice and

Men

• The Firmicutes have a higher capacity for breaking down complex

carbohydrates than Bacteriodetes

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Gut Microbiota

1: synthesize vitamins2: ferment complex indigestible carbohydrates

a mismatch of firmicutes and bacteriodetes bacterial species in small and large intestines

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““Gut Gut Dysbiosis”-Dysbiosis”-

Colonizers –Colonizers –

Alter the Bacterial Mismatch?

• Obese individual’s guts have a higher proportion of Firmicutes and a lower proportion of Bacteriodetes than lean persons*

• Can TCM change the ratio between Firmicutes and Bacteroidetes?

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*Ley et al., Nature 444, 2006

Salvia officinalis (Sage plant) Salvia miltiorrhiza (Danshen)

aka:Chinese Red Sage Rosmarinus (Rosemary)

• The extracts of these plants and a molecule identified is showing promise by their action on these fat cell enzymes:

• adenylate cyclase (stimulates) • Phospho-Di-Esterase (inhibits)

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• Salvia officinalis

» » Rosemary

»

» Red Sage

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Increased Fatty acid Increased Fatty acid metabolism and storage metabolism and storage of calories in fatof calories in fat

Increased Increased

pro-inflammatory pro-inflammatory cellular responsescellular responses

Fermentation of Fermentation of indigestible dietary indigestible dietary polysaccharidespolysaccharides

Increased Intestinal Increased Intestinal absorption of absorption of

mono-saccahrides and mono-saccahrides and short chain short chain

fatty acidsfatty acids

Increased liver fat Increased liver fat

(cholesterol) synthesis(cholesterol) synthesis

Increased circulation Increased circulation of activated dietary of activated dietary

fat contentsfat contents

?Role of Firmicutes bacteria in the Gut?Role of Firmicutes bacteria in the Gut

• The Japanese eat little fat and suffer fewer heart attacks than the British or the Americans.

• The French eat a lot of fat and suffer fewer heart attacks than

the British or the Americans.

• The Italians drink a lot of wine and suffer fewer heart attacks than the British or the Americans.

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Confused as to what to eat?!Confused as to what to eat?!

Eat and drink what you like–Eat and drink what you like–Speaking English is what kills you!Speaking English is what kills you!

-I. Knopf, Reader’s Digest OCT 2002-I. Knopf, Reader’s Digest OCT 2002

And the simple go home message!...And the simple go home message!...

Fiberoptic Visualization of the Gut

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Celiac D

isorders

Celiac D

isorders

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Esophagus Stomach Duodenum ColonEsophagus Stomach Duodenum Colon

Endoscopic Journey of GI TractEndoscopic Journey of GI Tract

Cases Diagnosed: Only Tip of the Iceberg

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Gut Biopsy PositiveGut Biopsy Positive

Genetic Genetic susceptibility: susceptibility: - DQ2, DQ8- DQ2, DQ8Positive serologyPositive serology

Latent Celiac DiseaseLatent Celiac Disease

Silent Celiac Silent Celiac DiseaseDisease

Normal Gut Lining CellsNormal Gut Lining Cells

SymptomaticSymptomaticCeliac DiseaseCeliac Disease

US study of 13,145 with 1st and 2nd degree relatives with celiac disease

• 1:22 with 1st degree• 1:39 with 2nd degree• 1:56 in symptomatic• 1:133 in none-at-risk

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How common is Celiac How common is Celiac inheritance?inheritance?

GI symptoms:– Chronic diarrhea– Malabsorption– Abdominal

distension– Weight loss

Other diseases at high risk for celiac:– Type I Diabetes (insulin

requiring)– Autoimmune

endocrine disease– Turner and Down’s

Syndromes

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Who should be tested for Who should be tested for Celiac?Celiac?

Patients with complaints and no other explanation is possible:– Short stature– Abnormal liver

function tests– Delayed puberty– Iron def anemia– Recurrent fetal loss– Infertility

Other conditions with possible association :– Irritable Bowel

Syndrome– Autoimmune

diseases– Peripheral

neuropathies– Cerebellar ataxia

(gait disorders)

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Who should be tested for Who should be tested for Celiac?Celiac?

Risks of Autoimmune Diseases for Celiac Patients

Age at diagnosis and Chance of developing autoimmune condition

4 – 12 yrs of age 16.7%12 – 20 yrs of age 27%Over 20 yrs of age 34%

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Typical Celiac Presentations

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Non Gastrointestinal Celiac (ATYPICAL) Presentations:

Most common age at presentation:

older child to adulthood-• Skin-Dermatitis Herpetiformis• Dental enamel defects• Thinning of bones/Osteoporosis• Short Stature• Delayed Puberty• Iron-deficient anemia • Hepatitis• Arthritis• Epilepsy

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“Mines” of Celiac Disease Were Found Among:

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RelativesRelatives Patients Patients withwith

short stature, anaemia, short stature, anaemia, fatigue, abnormal liver testsfatigue, abnormal liver tests

AssociateAssociatedddiseasesdiseases

autommune disorders, Down’s, Immune autommune disorders, Down’s, Immune deficiency, neuropathies, osteoporosis,infertilitydeficiency, neuropathies, osteoporosis,infertility

““Healthy” Healthy” groups:groups:

blood donors, students, general blood donors, students, general populationpopulation

Celiac Facts:

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Celiac disease affects 1% of Celiac disease affects 1% of healthy, average Americans. healthy, average Americans.

That means at least 3 million That means at least 3 million people in our country are people in our country are living with celiac disease—living with celiac disease—97% of them are undiagnosed.97% of them are undiagnosed.

The average length of time it The average length of time it takes for a symptomatic takes for a symptomatic person to be diagnosed with person to be diagnosed with celiac disease in the US is celiac disease in the US is four yearsfour years

Associated Celiac facts

• Breast feeding upto7-8 months with delayed introduction of gluten in the diet (after 5th--6th month) minimizes the risk

• Occurrence of infantile GI infections like rota virus increases the risk

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Old paradigm - Celiac is a disease of small intestine

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London, year 1938

New paradigm: multi-organ autoimmune disease

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Celiac disease- Celiac disease-

villous atrophy villous atrophy malnutrition, malnutrition, malignanciesmalignancies

Bone- Bone- osteoporosis, osteoporosis, fracturesfractures

arthritisarthritis

dental anomaliesdental anomalies

Skin & mucosaSkin & mucosa

DermatitisDermatitis

herpetiformisherpetiformis

aphthous stomatitisaphthous stomatitis

hair losshair loss

Reproductive-Reproductive-

miscarriage, miscarriage, infertilityinfertility

delayed pubertydelayed puberty

Brain- ataxia, Brain- ataxia, seizures,depressionseizures,depression

Carditis, Carditis, cardiomyopathycardiomyopathy

AnemiaAnemia HepatitisHepatitis

Dermatitis Herpetiformis

Red hives and blisters

Severe itching

Symmetric distribution

Gluten sensitive

90% have no GI symptoms

75% have villous atrophy

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By permission of Dr. A. Fasano

Dental Enamel Defects

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By permission of Dr. C. Catassi

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Aphthous Stomatitis- Aphthous Stomatitis- Mouth UlcersMouth Ulcers

By permission of Dr. C. Mulder

Treatment – 6 Elements in Rx

Consultation with a skilled dietitian

Education about the disease

Lifelong adherence to a gluten-free diet

Identification and treatment of nutritional deficiencies

Access to an advocacy group

Continuous long-term follow-up by a multidisciplinary team

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GLUTEN Allergy = Celiac Disorders

• Gluten is a specific type of protein found only in wheat, rye, and barley

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Say Bye Bye to Regular Bread

• White/ Wheat/ Marble/ Rye- BREADS

• Avoid- Bagels/Muffins/ Croissants/ Hamburger buns/ Scones/ Pizza

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Avoid Red Flags- Read Food labels

• Some are obvious: • wheat/ wheat gluten/ barley/ rye• Others are ‘hidden’: malt is made from barley and

hydrolyzed vegetable proteins-(contain wheat)Cereals- cream of wheat-cheerios-frosted flakes• ?OATS – some believe its safe; but in some it can

reproduce symptoms

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What? No cereals!

• Relax!• Corn and Rice based cereals are OK• But ensure there is no malt content

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What about pasta?

• PASTA IS MADE OF WHEAT!AVOID- Spaghetti/ Macaroni/ Shells/ Spirals

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BUT!There are

alternatives

• Label must read “100% gluten free”• ‘bread’ made out of rice or potato flour

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Say Hello to:

• Rice• Potatoes• Of course- there is ‘gluten free’ pasta = Rice

noodles!

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Can you eat meat?

• Only ‘breading’ is the culprit• Get ‘unprocessed meat’ without additives

(deli meat and hot dogs are processed)• Always check

labels for presence of gluten

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Make meals enjoyable

with:• Think of delicious foods and drinks-gluten free-• Eggs• Fruits• Vegetables • Milk products

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Warning for canned items! check Warning for canned items! check for additives that may contain for additives that may contain gluten!! (Includes processed gluten!! (Includes processed cheese spreads, flavored cheese spreads, flavored yogurts)yogurts)When dining out check out the When dining out check out the restaurant! Decoding a menu restaurant! Decoding a menu card is challenging- be bold card is challenging- be bold and ask the chef for a gluten and ask the chef for a gluten free meal!!free meal!!

• NO traditional-• Cakes• Cookies• Treats

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Avoid Pastry Aisles at the Avoid Pastry Aisles at the SupermarketSupermarket

But Can Enjoy!

• Sugar and chewy treats-

• Marshmallows• Gumdrops• Plain hard candies• Or specialty bakeries who can make

gluten free pastry!

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What about alcohol?

• Beers are out (malt based)• Wine and liquors are OK

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Goals for Celiacs!• Stay symptom free!• Even a little gluten can induce- gas bloating/ altered bowel movements/ weight loss/ feeling tired and weak• But always check with your healthcare provider before you

change the diet

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Irrita

ble Bowel

Irrita

ble Bowel

Syndrome (I

BS)

Syndrome (I

BS)

IBS- A diagnosis made by excluding other diseases

• Not very well understood • Features: • Persistent abdominal pain• Diarrhea or constipation• Flatulence (wind)• Bloated feeling• Cannot be explained by any other condition

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ROME II Criteria

• Presence of symptoms for 12 weeks or more- abdominal pain or discomfort which is relieved by-

1. defecation

2. associated with changes in frequency of stools

3. associated with changes in form or appearance of stools

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Explaining IBS:

• Increased hypersensitivity of Colon• Impairs QOL • Triggered by adverse life events• Increased reporting of physical/ sexual abuse• Increased anxiety/ depression

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Explaining IBS

• Excessive response to 5-HT• Abnormal brain response to gut sensations• Excessive stress response• Gut infections and post antibiotic gut altered

microbiota• Role of gut candidiasis

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What causes IBS?

• IBS symptoms 1 year after Salmonella gastroenteritis

(10 times more likely to have IBS)• a disorder of the brain-gut axis • Serotonin is involved• Altered tryptophan metabolism• 15% of population affected (F>M)

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Colonic bacteria: malfermentation?

• Produce short-chain fatty acids and gases like methane, hydrogen sulphide (High in IBS patients vs controls)

• Bacterial suppression reduced gas formation• Small intestinal bacterial overgrowth?

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Food intolerance related gas formation?

• 50% of patient report improvement after avoiding- • grains • dairy products• citrus• caffeinated drinks• yeast • potatoes and onions

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IBS: Gut-Brain Syndrome?

• Therapy- Patients are highly susceptible to drug side effects

• Antispasmodics• Opioids• Serotonin agonists (stimulants) – Alosetron,

Tegaserod (restricted use), and antagonists (blockers)Lubiprostone

• Antidepressants

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Serotonin / Tryptophan

• A neurotransmitter-• Regulates:• Gastrointestinal secretion• Motility• Perception of pain• It also regulates state of the mind• In IBS patients absorption of tryptophan metabolites

is decreased

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IBS summary:

• Cause unknown• ?Gut hypersensitivity to pain• ? Serotonin/ Tryptophan imbalance• Classified by major symptom-• Diarrhea predominant (IBS-D)• Constipation predominant (IBS-C)• Mixed (IBS-D/C)• Symptomatic management required

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To Summarize:

• Diet/Food allergies• Gut bacteria- ratios• Role prebiotics and Probiotics• Gluten sensitivity-

Celiac spectrum• IBS- Brain-Gut axis imbalance

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