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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.
3
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
4
Relative Bacterial Concentrations and pH of the gut
5
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
7
Of Mice and
Men
• The Firmicutes have a higher capacity for breaking down complex
carbohydrates than Bacteriodetes
8
Gut Microbiota
1: synthesize vitamins2: ferment complex indigestible carbohydrates
a mismatch of firmicutes and bacteriodetes bacterial species in small and large intestines
9
““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?
10
*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)
11
• Salvia officinalis
» » Rosemary
»
» Red Sage
12
13
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.
14
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
18
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
19
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)
20
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%
21
Typical Celiac Presentations
22
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
23
“Mines” of Celiac Disease Were Found Among:
24
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:
26
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
27
Old paradigm - Celiac is a disease of small intestine
28
London, year 1938
New paradigm: multi-organ autoimmune disease
29
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
30
By permission of Dr. A. Fasano
Dental Enamel Defects
31
By permission of Dr. C. Catassi
32
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
33
GLUTEN Allergy = Celiac Disorders
• Gluten is a specific type of protein found only in wheat, rye, and barley
34
Say Bye Bye to Regular Bread
• White/ Wheat/ Marble/ Rye- BREADS
• Avoid- Bagels/Muffins/ Croissants/ Hamburger buns/ Scones/ Pizza
35
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
36
What? No cereals!
• Relax!• Corn and Rice based cereals are OK• But ensure there is no malt content
37
What about pasta?
• PASTA IS MADE OF WHEAT!AVOID- Spaghetti/ Macaroni/ Shells/ Spirals
38
BUT!There are
alternatives
• Label must read “100% gluten free”• ‘bread’ made out of rice or potato flour
39
Say Hello to:
• Rice• Potatoes• Of course- there is ‘gluten free’ pasta = Rice
noodles!
40
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
41
Make meals enjoyable
with:• Think of delicious foods and drinks-gluten free-• Eggs• Fruits• Vegetables • Milk products
42
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
43
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!
44
What about alcohol?
• Beers are out (malt based)• Wine and liquors are OK
45
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
46
47
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
48
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
49
Explaining IBS:
• Increased hypersensitivity of Colon• Impairs QOL • Triggered by adverse life events• Increased reporting of physical/ sexual abuse• Increased anxiety/ depression
50
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
51
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)
52
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?
53
Food intolerance related gas formation?
• 50% of patient report improvement after avoiding- • grains • dairy products• citrus• caffeinated drinks• yeast • potatoes and onions
54
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
55
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
56
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
57
To Summarize:
• Diet/Food allergies• Gut bacteria- ratios• Role prebiotics and Probiotics• Gluten sensitivity-
Celiac spectrum• IBS- Brain-Gut axis imbalance
58