Understanding the Gut Brain:

Stress, Appetite, Digestion & Mood

Presented by:

Merrily Kuhn
RN, CCRN ( r ),
PhD, ND, PhD

Disclosure
Neither Dr. Merrily Kuhn, the presenting speaker, nor the activity planners of this program are aware of any actual, potential or
perceived conflict of interest

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Participants completing this program should be able to:

1. Describe key functions of the gut brain.
2. List several ways the gut brain regulates appetite.
3. Identify how stress contributes to digestive disorders.
4. Describe how inflammation of the gut can affect mood & anxiety.
5. List several disorders that can be effectively treated with probiotics.
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Understanding
the Gut Brain
Dr.
Merrily
Kuhn
Understanding the Gut Brain
Have you ever had a ‘gut
wrenching experience?’
(Anger, anxiety, fear, elation)
Troubled brain sends
messages to gut
Trouble gut sends messages
to brain
Should view as 1 system!!
Gut bacteria
Human beings – made of
10 billion cells
3 – 4 # of bacteria in gut
+ trillions on surface –
Outnumber us at least 10 to 1
Part 1: Understanding the Gut Brain
• What is the Gut
Brain?
• The GutImmune
System
• The Language of
the Gut brain
Understanding the Gut Brain
Why should we look &
understand the GUT??
63 million complain of chronic
CONTIPATION; 2.2 million –
diverticular diseases; 2 million –
gluten sensitive; too much GAS
Bacteria, genes, immune
system & hormones??
Gut bacteria
Gut flora:
Play a key role in nutrition
Synthesize: vitamins thiamine (B1),
folic acid (B9), pyridoxine (B6),
and vitamin K
Produce digestive enzymes to
absorption calcium, magnesium,
and iron.
1
 Genes Immune System
Immune system – begins
We are shaped by 23,000 in mouth – intestine
genes 90% of immune system
In gut bacteria (bacteria, is in gut
virus, fungi & others) Parkinson’s –lipopolysaccharide (LPS)
toxic gut bacteria
8,000,000 genes Alzheimer’s – neurofibrillary tangles,
So are they important?? plaque

1. What is the Gut Brain?

Neurotransmitters
Dopamine (D2) – = amounts
 brain & gut
Serotonin– 95% of all
Enteric
made & found in gut
GABA – mood stabilizer,
increases serotonin,
bacteria in gut create

Central Nervous System

Major Divisions
Brain & Spinal Cord
Central – brain & spinal cord

Peripheral – somatic & autonomic

Brain & 100 billion

Somatic – carries messages to
spinal neuron muscles
cord – Trillions of
Autonomic – internal processes
glia (support sympathetic (SNS), parasympathetic
brain cells) (PNS) & enteric
weighs 3 #

2
 Enteric Nervous System

Enteric – meshwork of nerve
fibers that innervate the
viscera (gastrointestinal
tract, pancreas,
gall bladder)
Enteric Nervous System
Embedded in lining of gut
“Distinct Entity” it is a complete
network of neurons,
neurotransmitters, and special
proteins responsible for
communications, "thinking,"
"remembering," and even
"learning”
Anatomy of the GI system

Mouth

Stomach – HCl – begins
digestion

Small intestine – sterile,
responsible for digestion
& absorption; lined with
villi

Large intestine – absorbs
water, 4- 5# bacteria
Role of Enteric NS

Functions autonomously but
is modified by PSN (vagus)
& SNS

When the vagus nerve is
severed, the enteric nervous
system still functions
ENS is autonomous
BUT also influences
the brain!!
2. Gut Immune System

Immune system
contains: blood, organs &
cells (0:39 – 2:26)

Epithelial cells: central
component of immune
system in gut
http://www.youtube.com/watch?v=gnZEge78_78 6 min
3
 Epithelial Layer Epithelial Layer

Largest area 4000 sq feet
3. Secrete IgA - prevents

Gut Flora help maintain the integrity infection
of this lining in 3 ways:

1. Converting unabsorbed dietary

Through immunological
sugars into short-chain fatty effects, the gut flora
acids, a major source of energy is also believed to
for epithelial cells to regenerate
themselves; assist in preventing

2. Adhering to the mucosa, forming allergies and down-
protective layer and blocking regulates inflammation
harmful bacteria

Gut Immune System The Gut Immune System

Macrophages: secrete chemical

Whattriggers immune mediators  cytokines
system development in gut?

Gut sterile in uterus

Birth canal, bacteria become signal
Cytokines:
to activate gut immune system

C- section – pick up bacteria on skin
Proinflammatory cytokines: cytokines that
surfaces & have different community coordinate inflammatory responses in the
of bacteria body

More colic •Tumor Necrosis Factor (TNF)a

Slightly rates of asthma &
allergies, 2X more obese by age 3 •IL1b, IL6

Gut Immune
Gut Barrier
System & Gut Flora

Work together:
3 barriers that work
together:

Crowd out bad bacteria – no
Mechanical barrier - mucosal
place to hang on to epithelial cells

Symbiotic relationship
1. neurons (afferent)

Microbiota allowed to grow,
2. endocrine cells
multiple & thrive, minimally
3. immune cells
being destroyed by host derived
Ecological barrier - gut bacteria
inflammatory mediators
Immune barrier – like the blood

Prototype peacekeeper – brain barrier
Bifidobacterium ( C section)

4
 Tryptophan
Body Defenses How do we
Mechanical Barrier produce 5-HTP
Serotonin?
The GUT
Serotonin
70 - 90% immune cells are found in
the gut start 1:02 stop 2:32
http://www.youtube.com/watch?v=5zl
J8CztFO8&feature=related Melatonin
Melatonin

Egg
white 1000
mg

Crab, lobster
Seeds – sesame, sunflower,
Nuts (Cashews, almonds)
Cheese (cheddar, Swiss (320
mg/4 oz))
Oat bran, Chia seeds

Enteric Nervous System Breast Feeding

Breast milk 1900 early – 95%
Supports development of neurons in
gut & gut wall Today – 75%
So premature &/or none breast fed –
high risk for diarrhea & necrotizing
enterocolitis
3 months – 33%
Seems to have memory – not breast
fed (trauma to gut wall) & being fed 6 Months - 13%
solid foods too soon leads to
infection & gut diseases later in life 12 months – 2%

5
 Breast Feeding
When contact with foods -
develop pathogenic ‘bad’
bacteria
During 2nd year of life sensory
learning to understand
environment – thoughts,
speech, mobility
Brain may be overwhelmed at
this time – (leaky gut) so can
not learn how to communicate
with environment -autism
Gut Barrier – Endocrine Cells

Hundreds of thousands
of endocrine cells
produce more than
20 hormones
– all target others
organs in GI system

CCK – gallbladder

Gastrin - stomach
3. The Language of the Gut
Pain
• GI diseases are accompanied by
pain
• Pain arises when CD4 from
immune barrier
• As microbiota are disturbed,
substance P mesenteric plexus
Etiology Autism???
1 in 88 in US
Genetic
Pesticides, water borne
chemicals, food preservatives
Perfumes – all have chemicals
that can be neurotoxic,
mutagenic & neuromodulatory –
affect neuroblastoma cells
inutero when mother is exposed
to products
So How Do
Things Go Wrong???
Diet, environment,
climate, stress,
illness, drugs, aging
Visceral- pain results from:

Direct inflammation of visceral
organ
inflammatory bowel disease
pancreatitis,
appendicitis,
occlusion of bile,
GERD, dyspepsia

Functional visceral disorders
irritable bowel syndrome
(IBS)
6
 Visceral- pain results from: Language of Gut – Gut Feelings

Cardiovascular disease
The more signals

(CV) – clots leaving the viscera,

Urinary syndromes - the more likely to
interstitial cystitis, ‘feel’ something
kidney stones
Messages carried by

Female issues - spinal cord to brain –
endometriosis often are not specific
– referred pain

Language of Gut Stress

Visceral sensations include: nausea,
bloating

All arrive at Insular Cortex in brain

Stress alters gut motor

Plays role in function:
emotions & body
homeostasis

affects peristalsis

Regulates the immune
experience more
system hypersensitivity to gut

Conscious desires – food,
drugs activity

Brain Actions of
Corticotropin-Releasing Factor
(CRF)

7
 Stress

Activation of corticotropin
releasing factor (CRF):

Contributes to delayed gastric
emptying

Increased colonic activity

Functional bowel disease (IBS)

Increase in gut permeability

Leaky gut – antigens leaking out

Toxic liver overload

Systemic disease
Part 2 Stress, Appetite
& the Gut brain
• 1. Review  Facts about gut
bacteria
• 2. Review Appetite
• 3. Starvation Response
• 4. Cortisol & chronic stress
• 5. Ghrelin & Leptin
• 6. Diabetes
• 7. Nutritional Approaches
Cortisol
• Cortisol receptors are located
throughout the central nervous
system.
• Hippocampus (limbic system), a
structure involved in learning,
memory and mood
• Prefrontal cortex (tries to shut down
cortisol release during stress
Part 1: Understanding the Gut Brain -
Summary
ENS is autonomous BUT also
influences the brain!!
70-90% immune system is in the gut
Need healthy gut for Serotonin
production
Healthy gut begins at birth
Many thing can go wrong – diet,
environment, stress, drugs, aging
Most times we are unaware of the
gut’s language, BUT visceral
sensations secondary to pain,
inflammation, stress, dysbiosis
can be felt by some!
1. Interesting facts Gut Bacteria

Changes:

with age

in pregnancy

with anxiety

Gut Bacteria Can Make Us
Fat – more energy
harvesting bacteria
8
2. Human Appetite
3. Starvation Response
• Designed for primitive
survival
Weight loss – drops
• Now calorie rich, calorie
metabolic rate, so
dense foods
• Primitive brain – need fewer calories
amygdala – fast for “STRAVATION
survival RESPONSE”
• Prefrontal cortex – slow
– uses problem solving
to change

4. Cortisol & Chronic Stress Cortisol

What does Cortisol Creates Belly Fat
Regulate? Sour stomach – too much HCl
insulin – more fat storing
Definition Ca++, K+ - more muscle
Acute VS. Chronic cramps
Water retention
Frequent urination
http://www.youtube.com/watch?v=Boy2B1oC
nWs
Forgetfulness & poor memory
Vasoconstriction in blood vessels

Causes:
Dieting, Job,
Effects of Stress
Family, Life
Metabolic – Syndrome X

Cortisol!!

9
 Brain
Gut Axis
Brainderived neurotropic factor
A neuroprotective protein
BDNF
Brain-derived neurotropic factor
A neuro-protective protein
• MAY BE RESTORED BY:
* Antidepressants
Seroquel
Lithium, Depakote,
Tegretol, Lamictal
* Exercise*****
size of hippocampus
* Omega 3, B vitamins
What Controls Weight?

Ghrelin & Leptin - both really
control the moment to
moment messages from the
gut to the brain about food
intake & fullness.

Ghrelin, Leptin &
hypothalamus- together
probably control body
weight by acting as
metabolic switches
Stress in Newborn –
Csection birth
• Inappropriate microbiota
• Creates BGA stress ( BDNF & 5HTP
production)
REDUCES TOXIC EFFECT of Cortisol
NEUROGENESIS (birth of
new nerve cells) in the
hippocampus – appetite
http://www.youtube.com/watch?v=CdTKxHhHZ1I
What Controls Weight?

Blood sugar & insulin

Ghrelin

Leptin

Genes

Gut bacteria

Environment
Ghrelin

Hormone released by the stomach &
pancreas

Potent appetite stimulating hormone

Triggered by less food

Increases hunger particularly for high
caloric foods (Do you always have
room for dessert?)

Slows metabolism

Decreases the body's ability to burn fat
10
 Ghrelin What Controls Weight?

Lipid sensor, has to be activated
by fat – from the diet not from
Ghrelin - negatively
the body

Activated by GOAT enzyme correlated with weight

Once activated, now signals us to
Obese people have lower
eat & store fat

Stimulates GH, Gives green light
serum level then lean
to brain to grow & use calories
So continue to eat!!!!

So eating fat, turns on ghrelin &
appetite

What Increases Ghrelin?

With Gastric Bypass

Reduces appetite and
improves metabolism
before substantial weight
loss occurs

Intriguingly, procedure
causes food to bypass the
stomach and gut
sections that contain
GOAT/ghrelin cells

Prevent ghrelin activation

Changes Gut bacteria

11
 Hypothalamus
5. Leptin: Weight Control
Orexigenic Anorexigenic
Leptin (1994)

Hormone produced in white
fat cells (white fat cells
store) (adipokine family)

Leptin allows fat to
communicate to the brain
Blood sugar

Helps regulate body energy
stores

Leptin: Weight Control

Leptin: When Leptin is
normal

Tells brain fat stores are
full, stop eating, not to
store more fat & begin to
exercise & burn fat

Leptin levels are
proportionate to fat

Leptin: Weight Control Overweight People

High levels in obesity so
Resistant to
most likely insensitive to leptin

Often resistant to
leptin, also insulin
insulin too!!!!! Leptin
resistance & pre- Resistance

NO longer .
diabetic Satiated –

Increases Inflammation EAT, EAT

12
 Can we Prevent Leptin: Fact
Resistance?

Ghrelin is in

Avoid: stress,
inflammatory foods competition

Increase Fiber & good fat with Leptin!

Increase sleep
Leptin is in

Increase exercise competition
with Ghrelin !

6. Diabetes
Environment
Diagnosis FBS 2 hr GTT
Available of F & V $$$$–
more meat

Normal
More Simple CHO –
More obese children
Prediabetes

Food is everywhere!!
Diabetes

7. What Foods inhibit Leptin

Diabetes
Resistance?

Prevention:

Exercise, weight loss
Diet
60% complex CHO
20% fat
20% protein

Diabetes changes gut
bacteria

13
 Source of alpha linolenic
acid – omega 3, lignans,
What Foods inhibit
Flaxseeds fiber - soluble
Starvation Response?
Seeds – soak or grind
¼ C /day
Bulk producer Oil - temperature sensitive
Capsules – not
Antioxidant recommended
TNF (reduced # breast
cancers & size of tumors)
Cholesterol (up to 18%)
Triglycerides (36%) Good evidence

Skipping breakfast 1 Big Meal / Day

FBS
4X risk of MI
with hypoglycemia - poor recall,
BP, HR, diabetes
poor exams & critical thinking

Turns on Ghrelin

Turnson ghrelin

21% higher risk of developing
Damages endothelium
Type 2 diabetes
As insulin spikes – relaxation of

MekaryRA, Giovannucci E, Willett WC, van

coronary arteries, more spasm
Dam RM, Hu FB. Am J Clin Nutr 2012
Poor sleep – easy to fall asleep
May;95(5):1182-9. Epub 2012 Mar 28.
but poor sleep maintenance

Excellent Diet Food additives, colors,

5 small or 3 moderate meals / preservatives, refined
day sugars,

Breakfast – whole grains &
protein (Whole grain ferments Genetically engineered – 1996,
in large bowel) gov. subsidized (wheat,

More satisfied, improves
concentration & memory corn, sugar beets, soy)

Fitbit.com
All alter gut microbiota &
http://www.fitbit.com/product


http://www.youtube.com/watch?v=gA2xEH2C7Fg&jt
can damage intestinal
=1&jmt=1&js=100&jsid=28097&jaid=38067&jcp=br wall
http://www.motherjones.com/tomphilpott/2012/09/gmo
and&jag=fitbit
cornrattumor

14
Feingold Diet
MSG
Can diet make a difference?
http://www.feingold.org
Are school lunch programs good &
healthy?
http://www.youtube.com/watch?
v=QSTZ6AdQdwk

High Fructose Good or Bad

Corn Syrup Food???
Soda - Liquid sugar – 14 TSP/12 oz can App for smartphone
Scan bar code & it will check for ingredients
Study demonstrated relationship – good & bad
Preservatives, GMO
between 1 soda & diabetes (Jr Clin Nut, Fooducate is NOT funded or influenced by
Dec ) food manufacturers, supplement
Sugary drinks 13% companies, diets, or any sort of
1 magic pill.
Artificially sweetened 6%
1
http://www.fooducate.com/about
Fruit juice ( risk of diabetes)

Dietary Lipids –
Good, Bad, Ulgy Poly Fats
Cholesterol
Saturated Fats (solid room temp)
Polyunsaturated
Monounsaturated (liquid room
temp) Essential – can NOT
be made in body

15
 Antibiotics
Findings:
Omega 6:3 Livestock producers  feed healthy animals
unnecessary antibiotics  and, as an
unintended sideeffect, breeding
bacteria resistant to antibiotics.
Practice undermines the effectiveness of
lifesaving medications.
Antibioticresistant strains of common
bacteria like salmonella and E. coli in
popular meats like chicken, ground
turkey and more.

Omega 9s
Fats in Diet -
Mono fats Summary
Fat LDL HDL Inflammatory
Sat
Poly 6
Poly 3
Trans
Mono

Take Home Message

Protect gut bacteria

Normalize Ghrelin, Leptin &
Fish Oil Capsules insulin
Omega 3’s
Remove chemicals, additives &

Omega 3s
pesticides from the diet

EPA (eicosapentaenoic acid) 180-300 mg whenever possible
DHA (docosahexaenoic acid) 120-200 mg
Eat regular meals

Omega 9s
CL.Com
Low glycemic foods always
Never Omega 6s
Protein at each meal
Tested 24
1 - 4 gm/da
Good fat
17 pasted
BUT 3 spoiled

16
Hormones that have an Effect on Food
Orexigenic (stimulate food intake) —
May act in the lateral hypothalamic
neurons
Neuropeptide Y (NPY)— is the most potent Pro-Opiomelanocortin (POMC) —
orexiant known; may respond to aberrant
leptin signaling; antagonism may reduce
hunger and fat mass
Agouti Related Peptide (AgRP) — potent
orexiant; may respond to absent leptin;
antagonism may reduce hunger and fat
mass
Melanin Concentrating Hormone (MCH) — intake
receives signals from NPY to increase food
intake
Orexin — increases arousal and food
intake
Ghrelin — a potent GH releasing hormone
released from the stomach, pituitary, and
hypothalamus; increases food intake and
body weight; may compete with leptin
Hungry, Hungry Hormones — Part 2
John M Berard
http://www.t-
nation.com/free_online_article/sports_body_training_performance_science/hungry_hungry_hor
mone_part_2y
Anorexigenic (reduce food intake) —
May act on the ventral & dorsal medial
hypothalamus
precursor to áMSH
Melanocyte Stimulating Hormone
(áMSH) — decreases food intake; may
respond to increased leptin;
antagonism increases appetite and food
Melanocortin 4 receptor (MC4R) — áMSH
receptor; binding of agonist reduces food
Cocaine Amphetamine Related Transcript
(CART) — decreases food intake; may
respond to increased leptin
CCK — gastric released peptide;
increases satiety; reduces food intake
(single feeding and meal frequency)
Corticotropin releasing factor (CRF) —
regulates adrenal hormones and ACTH;
decreases food intake, increases
energy expenditure
Insulin — increasing concentrations of
insulin decrease appetite
17
Fish Oil Information:
Omega 3s- EPA & DHA are found in fatty fish, calamari, krill & algae oils.
Small amounts can be synthesized from can be flaxseed, chia seeds, soy &
walnut oils which are sources of alpha-linoleic acid.

EPA (eicosapentaenoic acid) 180-300 mg

Heart protection, more antidepressant & anti-inflammatory
effect
DHA (docosahexaenoic acid) 120-200 mg
Nervous System protection
EPA 1.5:DHA 1.0
Omega 9s can be added but NEVER omega 6s

Recent research:
Review 20 studies, 68,680 patients, overall omega 3 supplementation does NOT
lower risk of CVD; sudden cardiac death; Sept 12, JAMA, 2012.
BUT 14 year study found fish oils reduced risk of dying & improved life expectancy
by 2.2 year; Ann Int Med 13.
May increase likelihood of developing prostate cancer – but cause & effect
undetermined. – JNCI 13
Dialysis patients with highest EPA/DHA levels , have lowest risk of sudden
death. Friedman, et al., Kidney Internat. 6 Feb 2013;
62% lower risk of nonfatal MI – (234 mg EPA/DHA) (deGoede, J. Nut,
2010)
77% lower risk of developing Ulcerative colitis –DHA 410 – 2000 mg
(Hart, 2009)
32% decreased risk of breast cancer, dose ? Brasky, Canc Epid Biomarker,
2010)
Prevents weight loss during chemo, 2.2 gm EPA, (Murphy, Cancer, 2011)
Blunts effects of stress. Am J Physiol, 13.0% less likely to develop diseases of retina
230 mg DHA, 100 mg EPA, (Christen, Arch Opthamol, 2011)
But did not slow macular degeneration. JAM A 13.
41% decrease in remission of depression in older women, 1670 mg EPA,
830 DHA, (Carney, JAMA 2009)
To RX depression, 1000-2000 mg EPA, use formulas with 60+% EPA, under
40% DHA (Lesperance, 2010)
20% reduction in anxiety, 2008. EPA, 348 DHA, (Kiecolt-Glaser, Brain
behav Immun)
Pregnancy & babies – increase DHA 800 DHA, 100 mg EPA, (Oken, JAMA,
2010)
Enhances memory in healthy young adults – 1160 DHA, 170 EPA after 6 months.
Am J Clin Nutr, 13.
Healthy elders (55 – 75) had 26% increase in executive functioning – fluency, visual
tasks & reading after 6 months, Cereb Cortex 13.

18
 Alzheimer’s – no effect
Age related cognitive impairment-DHA 1550, 400 EPA, (Sinn, Br J
Nutr, 2011)
Improved quality of life during lung chemo – 2 g EPA, 1 DHA. (B S van
der Meij et al. (European Journal of Clinical Nutrition (2012) 66,
399–404).

Good fish oil products – In recent testing consumerlab.com tested 36

products & only 24 passed. Do see this report before purchasing products.

Life extension 2 caps = (1400 EPA, 1000 DHA), USANA (290 EPA, 235
DHA), Omega Smart (780 EPA, 240 DHA), Douglas Lab (600 EPA, 400 DHA),
Solanova (290 EPA, 210 DHA)

Concentrated form of Omega 3 – OmegaBrite

Vegan – Algal oil – Natrol DHA 100 – 200 mg

Krill oil - Mercola EPA 90 mg, DHA - 50 mg (there are quality issues!)

For those concerned about the latest fear of fish oils leading to prostate
cancer, hear is a rebuttal from a noted researcher!

Greetings,

As you may be aware, an article published in the July 2013 issue of the Journal of the
National Cancer Institute suggests there is an association between elevated plasma
omega-3 fatty acid levels and a heightened risk of prostate cancer.

This study must be interpreted with a significant degree of caution for a variety of
reasons:

• The data came from what is referred to as a retrospective, nested, case-control

study. The data was extracted from another, much larger, previously conducted
trial that was not originally intended to examine the relationship between
omega-3 fatty acid levels and prostate cancer. In other words, the original
study was not designed to determine any of the conclusions reached in the
analysis contained in the article.

• The study's results conflict with the results from other studies that do suggest that
omega-3 fatty acids offer a protective benefit against prostate cancer; and these
other studies were, in fact, designed to analyze that very outcome. (See link)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629172/

19
 • Identifying one particular physiologic marker in a group of individuals with a given
condition - in this case, an elevated omega-3 level in men with prostate cancer -
does not prove causation, especially when that marker can be influenced by
diet or behavior and is only measured at a single point in time.

• It is also hugely important to realize that the authors of this study did not assess
any of the participants' dietary intake of fatty fish or omega-3 nutritional
supplements - the study's conclusions are based wholly on the results of a
single blood test.

• The omega-3 index, which measures both EPA and DHA within red blood cells,
is a much more accurate indicator of long-term omega-3 intake and tissue
status than is the plasma omega-3 level, which is subject to significant day-to-
day variability.

• A number of confounding risk factors might have influenced the purported

outcomes in the study, despite attempts by the investigators to account for
them:

1. 53 percent of the subjects with prostate cancer were smokers.

2. 64 percent of the cancer subjects regularly consumed alcohol.
3. 30 percent of the cancer subjects had at least one first-degree relative
with prostate cancer.
4. 80 percent of the cancer subjects were overweight or obese.

• Considering the extensive body of literature that supports the anti-inflammatory

effects of omega-3 fatty acids, there is no credible biological mechanism, nor is
one suggested in the article, that would explain why these essential fatty acids
might increase tumorigenesis.

Summary: Given the inconsistent data attributable to omega-3 fatty acids and prostate
cancer, and acknowledging the broad range of health benefits that are almost
universally accorded to omega-3 fatty acid consumption, it would be premature to stop
eating fish or to discontinue taking omega-3 nutritional supplements on the basis of this
study.

In Health,

Robert Rountree, MD
Chief Medical Officer
Thorne Research, Inc.

20
Stress & Digestive 1. Stress & GI Disorders Gut
Disorders • Major risk factor for Gut
1. Stress & GI Disorders disease
2. Inflamed Gut – Inflamed Brain • Affects # & type of bacteria
3. Inflamed Gut – Obesity
4. Causes of Gut inflammation; zonulin
• When stressed:
5. Irritable Bowel Syndrome (IBS)
Bacteroides, good bacteria,
6. Food Allergies falls by 20 to 25 percent
7. GERD

Clostridium, bad bacteria,
8. Inflammatory Bowel Disorders
9. Nutritional Approaches increases a similar amount

Stress & Cortisol

2. Inflamed Gut –
• During night, cortisol
production
Inflamed Brain
allowing for removal
of inflamed tissue to
• Chronic Inflammation (high
blood stream & liver cortisol) in gut – signals
• Insomnia, overwork, prefrontal cortex &
chronic stress hippocampus (60% co-
keeps cortisol up at morbid psychiatric issues)
night
Body can not clean up

Inflamed Gut –
Inflamed Brain
• Chronic Inflammation in gut
– allows for leaky gut
• Same junctions exist in brain
so toxins leak from gut &
go to brain to cause
inflammation

21
Inflamed Gut – 3. Fat is endocrine & immune
Inflamed Brain tissue
Here are some signs of an inflamed • Endocrine – adipocytokines by
brain: white fat
~ foggy thinking Leptin, resistin, plasminogen
~ poor short(term memory
~ difficulty concentrating
activator inhibitor, adiponectin
~ depression • Immune – cytokines
~ anxiety (inflammatory)
~ irritability TNF, Il(6, Il(1, monocyte
~ hyperactivity
chemotactic protein

TNF(α Inflamed Gut – Central Obesity

• Central obesity, Visceral fat,

Recognized risk factor for
fatty liver, type 2
diabetes, and CV disease
Fat packed in and between
abdominal organs
Metabolic X

4. Another cause of GUT inflammation Heterocyclic

Polycyclic Aromatic Hydrocarbons
(PAHs) & Heterocyclic Amine (HCAs)
Amine & PAH Protection

Found in fat

When fat or juice drips on coals
& burns

PAHs rise in smoke & deposit in
meat
Carcinogens!

Marinade ( flavoring, acid)
lemon juice, OJ, vinegar, (no oil)
garlic, soy sauce, ginger or FRESH
SPICES
red meat up to 24 hr
fish/fowl up to 2 hr

22
5. Irritable Bowel Syndrome

Also called spastic or irritable colon

Accounts for 25 – 50% of all GI referrals

Most common functional GI disorder
in the world ( 10 - 20% of Americans)
http://www.youtube.com/watch?v=DLXqH8h8
OH0 ( 4 min)
Irritable Bowel Syndrome

Definitely a gut – brain connection

50% also have:

Depression

Anxiety

Somatization (multiple physical
symptoms not explained by a
disease) or personality
disorders
12 weeks of abdominal pain
(usually L lower quadrant),
recurrent over last 12 months
C/D
Irritable Bowel Syndrome

1:5 (more common than asthma /
diabetes)

Male:Female ( 1:2, mean age 29

All age groups

Highest in incomes below $20,000,
unemployed, & unmarried

Key component of Gulf War syndrome
(1991)

57% develop after bout of food
poisoning

Develop after multiple rounds antibiotics
Irritable Bowel Syndrome

Absolutely

Affects quality of life

Presents a significant financial
burden

NO cure, Does NOT lead to Cancer

Symptoms persist despite a
negative exam for GI
abnormalities

Symptoms do NOT usually
interfere with sleep
Small Intestine Bacterial
Overgrowth (SIBO)

Colon (at least 1,000,000,000 bacteria per
milliliter (ml) of fluid)

Small intestine (less than 10,000 bacteria
per ml of fluid)

Bacteria are different

SIBO ( abnormally large numbers of
bacteria (at least 100,000 bacteria per
ml of fluid) in the small intestine &
resemble those found in colon
23
 Small Intestine Bacterial Small Intestine Bacterial
Overgrowth (SIBO) Overgrowth (SIBO)

Often treated with antibiotics

Interferes with muscular activity in • AMITIZA, prescription, multiple
the small intestine allows the side effects
bacteria to stay longer and • Linaclotide (Linzess) – with
multiply in the small intestine constipation

Since it is colon bacteria creates GAS
• SSRIs – SE GI bleeding???, violent
behavior, suicide risk………
NO MAJOR research is +

Irritable Bowel Syndrome Irritable Bowel Syndrome

SIBO – Treatment -DIET
SIBO - Treatment
Flax,ground seed, normalizes both

Probiotics, Bifidobacterium infantis 35624, diarrhea / or constipation
VSL#3 or Flora(Q for 1 – 2 weeks
Watch what you eat, avoid allergens

Lower sugars & CHO in diet

Reduce stress to decrease cortisol
Avoid FODMAPs (inability to digest

Avoid antacids (neutralize HCl) lactose, fructose, fructans, +) (

Peppermint encapsulated tabs (elimination diet for 6 – 8 wks, than
add back)

Irritable Bowel Syndrome Irritable Bowel Syndrome

FODMAPs
F - fermented CHO FODMAP diet
O –oligo-saccarides
D – di-saccarides Oatmeal, lactose free milk,
M – mono-saccharides
P – polyols (lg sugar molucules)
strawberries, walnuts
i Spinach salad, grilled
FODMAPs pull extra H2O (20%) into intestines =
diarrhea, more gas & bloat chicken, oil & lemon juice
dressing, orange
Avoid: Lactose (milk, yogurt), fructose (apples,
figs, mangos; wheat, ice cream, honey) ,
fructans (Inulin); wheat flour, honey, agave
Salmon, Baked potatoes,
Have a cumulative impact on symptoms greens & carrots
Jr GI Hepatology, 2010; Clin GI
Hepatology, 2008; Jr Human Nut, 2011

24
6. Food Allergies
Histamine
• In an attempt to "protect" the body,
immune system produces IgE
antibodies to that food
• IgE antibodies trigger mast cells
(allergy cells in the body) to
release histamine (released in
gut as well!) resulting in watery
eyes, running nose, sore throat,
or lung, skin, or GI tract and
symptoms
Food Allergies
Symptoms
Uncomfortable to life threatening
Tingling or itching ( mouth
Hives, itching or eczema
Swelling ( lips, face, tongue and throat
Wheezing, nasal congestion or trouble
breathing
Abdominal pain, diarrhea, nausea or
vomiting
Dizziness, lightheadedness or fainting

Food Allergies Food Allergies

Who develops? Foods

Family history Dairy – milk***
Soy***

Early exposure (peanuts in Egg***
house before 1 year) Fish, Shellfish (only 5 – 10% out grow)
Nuts (only 1 in 5 will out grow)

Premature Grains – wheat***

C-section babies (higher Fruits & vegetables
allergy rate) ***Most common in children,

HX of allergy - asthma most outgrow by teens

Wheat Belly
Food Allergies http://www.youtube.com/watch?
v=uexJlVLbDzI
Management
Elimination Diets Celiac Disease
Avoidance – read labels
3 million have it, less 5% DX !!!
Food allergy testing (IgG
Recognized all over the world
ELISA/EIA panels –?? Efficacy, not
reliable)
Intolerance to gluten

Immunotherapy injections - ???
3 min

Immunotherapy - oral
http://www.youtube.com/watch?v=EmZczwtsb
Vc

25
Celiac Disease
 Described 1888
 Linked to gluten (wheat, rye,
barley) WW1
 T-cell mediated inflammatory
disorder with autoimmune
features
 Triggers humoral & cellular
immunity
 Leads to NK cells & TNF
(interleukin) = damage
Celiac Disease
Pathophysiology
Uppersmall intestine
(duodenum & jejunum)
Decrease in intestinal
hormones – Malabsorption
of most nutrients in the
presence of gluten
Celiac Disease
Pathophysiology
Mg++ & Ca++ loss leads to
seizures & tetany
Also more phosphate
excretion – so more bone
reabsorption
Fat malabsorption causes
steatorrhea
Celiac Disease
Etiology - polygenic
Genes – 40 %
So families are a high risk
Environmental factors – lack of
breast feeding, amount &
timing of gluten in infancy
Due to hybreeding – gluten has
500 fold today
Celiac Disease
Pathophysiology
Increased shedding of epithelial
cells causing hypertrophy of
crypts
Even with hypertrophy, cell
productions can not be
maintained so villi atrophy &
flatten
Celiac Disease
Pathophysiology
Fatsoluble V deficiencies –
vitamin K – bleeding &
clotting issues
Deficiencies of folate, iron &
B12 so anemias
26
Celiac Disease
Treatment

Gluten(free diet
70% improve in few weeks
biopsy may not improve for
years (Placebo effect???)

Find & eat ancient grain – not
genetically engineered

Also assume lactose intolerance

Inhibitors of zonulin???

Zonulin

Celiacdisease &
other autoimmune
diseases, excess
zonulin causes
gates to stay
open allowing large
molecules –like
wheat – to enter the
blood stream
Celiac Disease
Treatment So what can I eat?

Grains – Teff, rice, amaranth,
Quinoa, millet all OK

Oats ( OK after time (but may be
contaminated with wheat)

These grains are NOT fortified so
need
Bs – Folate & B12, iron
Zonulin
Regulates permeability of gut
wall
Acts as gatekeeper, traffic cop
2 large barriers : Gut barrier &
Blood(brain barrier
Fascana,Ann N Y Acad Sci. 2012
Jul;1258:25-33
Zonulin
Could also be indicated in:
other autoimmune
disorders such as insulin
dependent diabetes,
multiple sclerosis, and
rheumatoid arthritis
Treatment: inhibitors of
Zonulin
What Does Gluten Free Really
Mean????
4 min
http://www.youtube.com/watch?v=UHF2z
SfAp8Q
Gluten in Food

Soups, sausages, ice cream often
contain gluten as a filler

FDA – if product has less than 20
parts / million, can label the food as
‘gluten free’

Drugs have gluten – DO NOT have to
mention gluten on the label

Glutenfood.com
27
Gluten / Casein & Autism 7. GERD

Autism spectrum diseases

Often experience GI disorders Symptoms

Elimination diets gluten, casein
(dairy)  Dyspepsia

DAN ( Defeat Autism Now)  Retrosternal or substernal
Protocol – suggests 85% chest pain
improvement (heavy metals –
mercury; yeast; food intolerances)  Increased salivation

http://www.miriamjangmd.com/D
efeatAutismNow(protocol.html  Regurg

GERD GERD

Symptoms Associated Conditions

Dysphagia – narrowing of Dental erosions
esophagus Obesity
 Odynophagia – painful Sleep apnea
swallowing
Asthma (1/2 of adults have
 Atypical chest pain reflux, usually 2 – 3 AM)
 Eructation, Nausea & vomiting
Frequent pneumonia

GERD GERD
Determine triggers
Determine triggers-Diet
acid production
Relax sphincter
 peppermint, chocolate
 tomatoes  spicy foods
 citrus Acid foods –
 caffeine
 dairy juices-
 alcohol – red wine, brandy
 garlic
orange juice
 colas, carbonated drinks

28
 GERD GERD
Teaching Treatment
 sm frequent meals Stop drugs that aggravate
 no tight clothing  Asthma drugs, BCPs
 HRT (progesterone inc heart burn)
 dec weight  ASA, NSAIDs
 no supine for 3 hr pc meals  Ca++ channel blockers
 Demerol

GERD GERD
Treatment NEW Therapy - LINX
Drugs Therapy Overview (4 min)
Prokinetic agents  Cost:
Antacids  Device $5000
PPIs later
H2 Antagonists  Procedure $12 ( 20000

http://www.youtube.com/watch?v=RaCFhd
https://www.youtube.com/
7B5x4 watch?v=X4dmjT-t2oc

9. Inflammatory
GERD
Bowel Disorders
Treatment Hypothesis ( IBD is the
Complementary consequence inappropriate
immune response against the
 DGL licorice – ac, bedtime normal gut microflora
 Chamomile tea – soothes Characterized by periods of
quiescence interspersed with
 Flaxseeds, psyllium
active disease
 Ginger tea –

29
Inflammatory
Bowel Disorders
30 % have comorbid depression

During exacerbations – 60 ( 90 %
experience depression

Crohn’s Disease Crohn’s Disease

Family tendency ( gene

mutations – overly Etiology
aggressive response to
normal bacterial flora) Autoimmune,
MAYBE BAD BACTERIA
leukocytes (prostaglandins, !! Only Western
leukotrienes, proteases, NO = cultures
more inflammation & injury), Fructose intolerance??
cytokines (Il, TNF-α)

Crohn’s Disease Crohn’s Disease

Treatment – Traditional

Pharmacology
Pathophysiology
SSRIs, other antidepressants [Tricyclics],
Inflammation steroids, antibiotics, antispasmodics,
fissures & abscesses sulfasalazine (Azulfadine), mesalamine (Asacol,
Pentasa), azathioprine (Imuran), 6-MP
strictures so lumen narrows (Purinethol), cyclosporine, methotrexate,
Fistulae may form in perianal area infliximab (Remicade)
between loop of intestine or extend
Psychological / behavioral therapy
into the bladder
Education
Hemorrhage
Diet

Checking for allergy /food
intolerances

30
Crohn’s Disease Naltrexone (LDN)
Research: Dr. Tom Gilhooly
Treatment – Complementary
(Scotland, highest level of MS in
Low FODMAP diet world)
To decrease inflammation: Clinical trails in US
Melatonin
Lowdosenaltrexone.org
Fish oils
Probiotics http://www.youtube.com/watch?v=pGcnz
Curcumin y8Gv5E

Ulcerative Colitis
Facts & Risk factors Ulcerative Colitis
Traditional Treatment
700,000
Anti-inflammatory drugs
Sulfasalazine (Azulfidine), Mesalamine
25% DX childhood (Asacol, Lialda, others), balsalazide
Peaks 20 – 40 yr of age, = M & F (Colazal) and olsalazine (Dipentum0;
corticosteroids
Higher social/economic level
Immune system suppressors
Family History Azathioprine (Azasan, Imuran) and
Jewish descent mercaptopurine (Purinethol);
Cyclosporine (Gengraf, Neoral,
More prevalent among whites Sandimmune); infliximab (Remicade);
Less common in smokers adalimumab (Humira)

Ulcerative Colitis Interesting Question

Complementary Management Do YOU need to clean your
Same as Crohn’s colon?
Gut bacteria transplant – 10 children,
(Children’s Hosp. Grand Rapids, MI) No scientific evidence that
5 enema in 1 week,
cleansing is helpful in any way!
67 reduced symptoms
33 - remission Dr. Mishori, Georgetown Univ. Med
Center, Washington DC

31
 Interesting Question
Interesting Question
Do YOU need to clean your colon?
Dr. Raj, a gastroenterologist at NYU Do YOU need to clean your
Langone Medical Center in New colon?
York, warned that cleanses are
potentially dangerous - Can cause To increase colon activity:
death Exercise - yoga, walking
V & M losses, dehydration & Fiber
Supplements are highly
Fluids
recommended by practitioners
Dr. Mishori, Georgetown Univ. Med
Center, Washington DC

10. Nutritional Approaches to

Reduce GI Inflammation Anti-
Resveratrol (anthocyanidins) inflammatory

Pinot Noir (most)–
resveratrol (mold- best Decreases
organic- no pesticides Substance P
sprays)– antioxidant / TNF-α, Il
anti-inflammatory effect CRP

Neuro-protective

Anticancer

Curcumin Curcumin
Anti(inflammatory –
BCM95 -Dolcas-Biotech, LLC.
irritable bowel syndrome (German CO )
inflammatory bowel disease vailable as Curcu-Gel Ultra
joint disease, 60 caps $24.00
liver disease Solanova 500 mg
cancer prevention Rick 800 200 0456
Aggarwal,
Aggarwal, MD Anderson Center, 2011

32
 Capsaicin

Induces apoptosis fat cells

Body fat & white fat (more
central)

Inhibit adipogenesis

Inflammation in macrophages

Protects from diet induced
obesity
Menthe
(peppermint oil)

Enteric coated only

Significant abdominal pain

gas, bloating & other IBS
symptoms
NOTE WELL: not for GERD
symptoms
Human Gut
Flora

If gut flora are damaged, they
can not chelate & toxins are
allowed to cause more damage
to gut wall – more leaky gut

If mom has damaged gut flora,
passes it on to fetus (autism??)
Ginger
(gingerols, zingerone)

Soothes upper GI

inflammatory
hormones

nausea (cancer,
motion sickness)
Human GUT

Stomach has HCl – designed
to breakdown protein

SO, we have difficulty eating
raw vegetables

Cell wall of Gut bacteria are
chelators hold mercury,
arsenic, other heavy metals
& eliminate
Fermented
Food

Are the best chelators

Detoxify & draw out wide
range of toxins & heavy
metals
33
 Yogurt, Kefir,
buttermilk, sour
Fermented GAPS (GUT and
cream, crème fraiche,
Kombucha, Kimchee Food Psychology Syndrome
(Napa cabbage) Book) Nutritional Program

Small quantities, ¼ ( ½ Cup
Dr. Weston Price
fermented vegetables/day
Dr. Natasha Campbell(McBride

Greater the variety the
RX: autism, learning disabilities,
better neurological disorders, MS, RA,

Each food inoculates gut with OA, psychiatric disorders,
a variety of different immune disorders, and digestive
microorganisms. problems

Part 4
Mood & Anxiety Disorders
1. Interesting Facts
Anxiety, insomnia, panic disorders &
addiction have tripled since 1980
In addition:
Obsessive Compulsive Disorder
Insomnia
Fibromyalgia, CFS, IBS, autism

Do these Conditions have 2. Deficiencies:

anything to do with Gut?
Serotonin Production
Brain chemicals
1. We eat amino acid tryptophan
Deficiencies Excesses
2. Converted to 5(HTP in small intestine
Serotonin Histamine 3. 5(HTP converted to serotonin in brain
GABA Glutamate
99% of serotonin deficient people fail to
Taurine Dopamine perform the 2nd step
Estradiol NE
Progesterone Gut bacterial issues!!
Mg++

34
 GABA
Powerful brain relaxing
chemical
Eat AA glutamine (proteins)
Glutamine glutamate
Glutamate into GABA by enzyme
in gut
With leaky gut (gluten intolerance), leak
the enzyme responsible for conversion ,
so more stimulating glutamate & less
relaxing GABA
Estrogen
Enhances serotonin receptors

When estradiol below 60(80 pg/DL,
receptors closed

Menopause, post partum,
serotonin deficiency occurs

Abnormal gut bacteria –
Candida( also interferes
with other hormones
Magnesium (MG++)
• Mg++ competes with Ca++ to enter
cell, Mg++ reduces electricity
• 60 – 80% of Americans have Mg++
deficiency
• Excessive Candida overgrowth
causes more Mg++ wasting by
kidney
Taurine
Calming brain chemical
Enhances GABA
If bacterial overgrowth, Taurine
is wasted & excreted by kidneys
Now more anxiety & insomnia
Progesterone
Calming brain hormone
Activates GABA receptors
Progesterone begins to 8 years
before estrogen
With bacterial overgrowth
(Candida), FSH & LH are , so
even less progesterone
produced by ovaries
Environmental Toxins
Toxins:
Taking a shower or drinking chlorinated


water (pesticide) ; we inhale chloroform
a by(product of chloride, we inhale
more chloride in a 10 min shower than
drinking 8 glasses of water from the
tap!
http://www.foodrenegade.com/chlorinated(
showers(baths(kill(gut(flora/

Heavy metals, plastics, pesticides (NEVER fruit
from CHILE) Styrofoam, Triclosan (liver
thyroid dysfunction)
WWW.grinningplanet.com/2005/10-
WWW.grinningplanet.com/2005/10-04/triclosan-
04/triclosan-article.htm

Drugs
35
 Environmental Toxins
Toxins –

Food we eat (hormone laden
produce & dairy, omega 6,
transfat

Arsenic (in rice [baby food?], brown
rice syrup), high fructose corn
syrup, chemically lined cans or
aluminum water bottles with
BPA)

Use stainless steel drinking bottles
Management
• Drugs – maybe
• Fix gut – stop leaky gut
(administer glutamine), TX
Candida
• Exercise
• Fix all deficiencies & excesses
• Reduce intake of antibiotics
Is all fat the same?
• White adipose tissue (WAT) ( obesity
phenotype – stores energy as
triglycerides in large droplets;
interfere with GLUT4 activity; along
with TNFα α contributes to insulin
resistance
• Brown adipose tissue (FIT fat) (2009)
(BAT)– lean phenotype; burns
triglycerides to produce heat for
protection against hypothermia &
obesity; Enhances insulin
movement on GLUT(4
Excess: Histamine
• Chemical structure almost identical
to dopamine & even activates
dopamine receptors in brain
• With leaky gut, more histamine
released from mast cells
• Note red flush – face, chest, lower
neck – dermographia – really
histamine flush
2. How Fat Cells can Make
us Depressed
Fat cells:

Attract inflammatory cytokines

Create Chemical messengers
that reach the limbic
system, Prefrontal cortex

cortisol
http://www.youtube.com/watch?v=1TtPNobccaY
Is all fat the same?
• What can affect the conversion from
WAT to BAT?

BDNF – key to energy
homeostasis; injections (mice)
induces browning of WAT;
mediates anti(cancer effect

Orexin – neuropeptide, key
stimulator for BAT activity
(Next obesity drug???)
36
3. Antidepressants & Gut 4. Antidepressant Affects
Motility Inflammation
• Antidepressants ( reduce anxiety • Known facts:
and pain sensations
Duloxetine (Cymbalta)
• + effect on gut motility and along with anti(
visceral hypersensitivity inflammatory, reduces
• "off(label" use of the drug, no pain of arthritis
FDA approval
• Compare side effects:
• SSRIs work well in constipation
• Tricyclics – have anticholinergic
Duloxetine (Cymbalta)
effect so prolong transit – NSAIDs & ASA
works well with diarrhea

5. Anti(inflammatory Fish oil

foods as Antidepressants Research Evidence
Fish Fish oil:
• anti(inflammatory cytokines in serum – Il10
• Serotonin production Pro(inflammatory cytokines – TNFαα,
improves universal blood flow interleukin, COX(2
in brain (in depression see holes Pain of arthritis, need for some anti(
with no blood flow) inflammatory drugs
• Japanese, Eskimos – have fraction Depressive symptoms BUT not when
of depression as US accompanied with anxiety (400 people, 8
• Meat eaters have high level of weeks, 1050 EPA, 150 DHA)
arachidonic acid (Omega 6 –
pro(inflammatory)

Fish oil ( Proof???

• Bipolar Depression Study (took 10 gm
refined fish oil / day
• After 4 months of 9 month trial,
STOPPED due to wide divergence
in study group & placebo group
• Supplement for depression ( 4 gm. EPA
• Eat wild salmon (canned is wild)
• Depression in pregnant women
after 8 weeks, safe, no side
effects
Krill oil – Yes or NO????
• Expensive to harvest –
• 3 manufacturers, problems of
quality associated with 2
Consumerlab.com for
quality products
• Check labels:
• 150 mg EPA, 90 DHA

37
 Pre( & Probiotics
History of Food
More on gut bacteria
Probiotics & Prebiotics – what are
they & what is the evidence?
Uses : General health, Immune
disorders, GI tract disorders,
Stress ( related disorders,
Oral Health
Evidence based guideline
History – Food
All has changed with the advent
refrigeration, sterilization,
pasteurization (dairy) and
other processing
Food sterilization has reduced
consumption of beneficial
organisms previously consumed
daily
Consume very few fermented foods
Gut Bacteria
• Bacteria living in gut 90%
are “good” bacteria
http://www.youtube.com/watch?v=RQbNuuIzWnA
• 60% of approximately 200
strains remain constant for
5 yr
Is One Diet Perfect for all?
• NO 2 people are same (
Your Fingerprint established
by age 2
We are: 89 – 90% different
History – Food
Before modern times
live bacteria and other
microorganisms were
commonly eaten in food
and used to preserve food
Human GI tract evolved to adapt
to a more-or-less daily supply
of live lactic-acid producing
bacteria
Body Bacteria
Belly button bacteria – 200
people
4000 different strains of
bacteria
NOT 1 STRAIN COMMON TO
ALL!!
Food & Gut &
Epigenetics
&feature=related
• DASH Diet
• Mediterranean Diet
• Paleo Diet
• Dukan Diet
• Low CHO, Low Fat, High Protein etc……
38
 Gut Bacteria Gut Bacteria
• Stimulate: Suppress

immune system microorganisms

digestion Good:
causing food

generate vitamins Lactobacillus poisoning

help body absorb nutrients
Bifidobacteria Release phytochemicals

keep lining of GI tract intact (to
prevent leaks) Bacteroids
• Gut bacteria: Saccharomyces

Modern diet boulardii (yeast)

Whole food

Gut Bacteria History ( Probiotics

Bad:
Bad, are responsible
Salmonella for DIARRHEA and Marco Polo
Shigella many disorders Discovered 1908
E. Coli
Definition – ‘means for life”
Bacteroides fragilis WHO 2002
Campylobacter,
Clostridium difficile (C.
diff)

Probiotic Criteria Probiotic Criteria

Organisms must be consumed live
Must be able to survive the host’s
digestive process and still
function
Must be able to colonize the gut in
high(enough numbers that
they can be identified in the
stool
Must be able to attach to and
adhere to the lining of the GI
tract in order to interact with
the GI immune system
Ideal probiotic elicits local and
possibly a systemic immune
response

39
 Probiotic Criteria Probiotics - 3 names
Lactobacillus acidophilus DDS(1
Should have been clinically tested genus species strain
with scientific rigor
Lactobacillus
MOST have NOT
Continued use is necessary to
Bifidobacterium
permanently change gut flora Saccharomyces
Streptococcus

Lactobacillus Probiotics - Action

over 50 species
Used for: yeast infections, urinary tract
infection, irritable bowel syndrome,
antibiotic(related diarrhea, traveler's
diarrhea, diarrhea resulting from
Clostridium difficile, treating lactose
intolerance, skin disorders (fever blisters,
eczema, acne, and canker sores), and
prevention of respiratory infections.
• Lactobacillus reduces cortisol &
improves disorders of mood &
anxiety
• Lactobacillus acidophilus &
Bifidobacteria improve IBS,
diarrhea, peptic ulcers &
lactose intolerance & celiac
disease – some studies

Probiotics - Action Probiotics - Action

Lactobacillus plantarum Lp299v ™
Is not killed by stomach acid Lactobacillus rhamnosus
marked effect on GABA
Can bind to gut wall
lowers cortisol
Can be grown in plant materials:
resulting in reduced
fruits (berries) and oatmeal –
anxiety, depression
so safe for lactose
intolerant

40
 Other Probiotics
Bifidobacterium – over 30 species
Used for: IBS, dental carries, improves
lipids & glucose tolerance,
Saccharomyces boulardii – only yeast
Used for: antibiotic & travelers diarrhea,
??? C diff diarrhea
Streptococcus thermophilus
Produces lactase
Probiotics - Action
• Recolonize small & large intestine
to crowd out disease
causing bacteria
• Restore acid balance to
intestinal flora – lactic acid
• Improve digestive health
• May dampen signals coming
from the gut to the brain
Improved cognitive function &
memory performance
Bs ( B12 – 100 mcg,
Folic acid – 400 mcg
Better to aim at prevent
Vit B12 – keeps brain from shrinking
& improves memory (keep level
at least 550 pg/ml – mid level)
Aim for 2.4 mcg of B12 in multi
Probiotics - Action
Bifidobacterium ANIMALIS
SUBSPECIES LACTIS BI(07
Can maintain flora even with
antibiotics present
Bifidobacterium
Babies who have more
in 1st year, less likely to be
overweight by 7
Probiotics ( Action
May change how brain sees &
responses to environment –
resulting in less stress, anxiety
& depression
Do not overgrow or take over the
gut
Produce vitamins – B complex
(biotin, thiamine, pantothenic
acid, pyridoxine, folic acid,
B12), K
Probiotics - Action
• Inhibit pathogenicity of bacterial
toxins
Saccharomyces boulardii &
Saccharomyces cerevisiae
• Boost immunity – Lactobacillus
spp.
• Encourage immunomodulation
41
 Probiotics - Action
• IgA antibodies – recognize &
fight foreign invaders
• # inflammatory mediators –
help heal inflammation
• IgE antibodies – “allergic(
specific antibodies “ found in
mucous membranes, skin,
lungs, that cause body to fight
pollens, dander, fungal spores
Probiotics - Action
• Release antibacterial substances
– bacteriocins – selectively
reduce growth of bad bacteria
• Produce other substances – lactic
acid (to acidify the bowel) (
preventing bad bacteria (E. coli
& Clostridium spp.)
Prebiotics
• Encourage growth & activity of
good bacteria
• Non(digestible fibers
(oligofructose, polydextrose,
fructooligosaccharides
galactooligosaccharides (sugar
molecule is stacked) & inulin)
Probiotics - Action
gut’s defensive barrier –
Lactobacillus spp. ( attach to
adhesion sites so bad
bacteria have no place to
attach – when it breaks
down – “leaky gut”
Probiotics & Prebiotics
(defined in 1995)
Synbiotic
• Combining both pre & pro in
same bottle:

Lengthens shelf life as probiotics
have food

Lengthens active time in gut
Inulin
• Inulin is a fructan, a soluble fiber,
created by soaking chicory root
• Completely fermented in colon!
• May diarrhea, gas (above 5 gm.),
bloating
• Feeds bad bacteria TOO (Klebsiella,
Candida) indicated in Ankylosing
Spondylitis, leaky gut & diarrhea
42
 Inulin Prebiotics - MUST
• Inulin – also known as
• Beta(2-1)fructans • Be resistant to stomach acid
• Chicory Extract, Chicory Inulin
& host enzymes( not
digestible
• Dahlia Extract
• Long-chain Oligosaccharides • Be fermented by gut
microbiota
• Prébiotique
J Am Diet Assoc. 2010 Jun;110(6):865-8

Prebiotics - ACTION Prebiotics - ACTION

• Aids water & electrolyte
reabsorption
• Produces short chain fatty
acids (SCFAs) – maintain
lining of bowel
• Increases activity of immune
function
• Increase mineral absorption
(Ca++ by 20%)
• Encourage ‘cross talk’
• Prevents bad bacteria from
clinging to epithelial lining
• (if can’t cling, can’t cause
harm)
• Decrease inflammation & colon
cancer

Prebiotics Foods
Artichokes Leeks
****Bananas Oats
Barley Onions
Beets Soybeans
Chicory Wheat
Flax By-products
Garlic of milk

43
 Auto-Immune Diseases
Hallmark is inflammation
All have abnormal Gut flora!
Lactobacillus in low in all
Foods rich in Lactobacillus
Yogurt , Kefir
Non(pasteurized fermented food –
sauerkraut, pickles, Kimchee
Miso
GI Tract Disorders
IBS (mixed + / ():
2 C plain yogurt with
Bifidobacterium for 4 wks
same results as just plain yogurt
NO probiotics – fermented food
may be the secret (BMJ, 2013)
GI Tract Disorders
IBS :
Lactobacillus reuteri
200 million/da 4 wks. kids,
Significant reduction in
abnormal pain, (Romano,
2010)
Other studies (
come up empty!
Probiotics
GI tract disorders – support brush
border of intestinal wall
which protects
IBS
Irregularity, Diarrhea (antibiotic
associated)
Celiac
Inflammatory bowel disease
Colic
GI Tract Disorders
IBS :
Bifidobacterium infantis 35624 (Align)
bloating & gas, NOT # of
stools (Whorwell, 2006)
Lactobacillus casei (Culturelle)
Significant reduction in abd
pain
Diarrhea
Lactobacillus reuteri and
Lactobacillus acidophilus
incidence of diarrhea in
nursery school children
44
 Diarrhea C Difficile Diarrhea
15 – 30,000 die each year
Antibiotic related Diarrhea – occurs
in 30%, probiotics reduce risk by Incidence goes up with
42% (Hempel, 2012) multiple, broad spectrum
Lactobacillus spp. ( reduces 42% antibiotics, PPIs
Saccharomyces ( reduces risk by (Gia, 2010; Ann Intern Med. 2012])
52% & prevents C diff diarrhea
66%; 10 billion /da
(Johnston, Ann Int Med. 2012)

C Difficile Diarrhea Stool transplant

Stool transplant – found
evidence of use over 1700 ( 25(90% effective at
years ago! significantly decreasing or
eliminating symptoms of
106 research studies – 90%
ulcerative colitis and IBS(C.
success rate (245 out of
273 had resolution of
( https://www.youtube.com/watch?v=(
symptoms!!!!!) gQbyoMmJ_k (start 2:30 ( end
Am J Gastroenterol. 2013 Apr; Am J Gastroenterol. 2013 Feb;
Am J Gastroenterol. 2012 Nov.

FMT – Fecal Microbiota FMT – Fecal Microbiota

Transplant Transplant
Procedure–
Donor Screening– Extract of healthy stool bacteria
Excellent health from extensively screened
Medical evaluation to donor is suspended in a
exclude autoimmune, solution
atopic, metabolic, mood, Preserved at (78 degrees Celsius.
and other disorder Solution is re(warmed, delivered as
No antibiotics for 6 months enema
Retained for around six hours.

45
Traveler’s Diarrhea
Out of USA
10 million each year
3 or more stools in 24 hour
Bug: E coli
Prevention: 20 – 30 billion / da Before
trip eat yogurt , Kefir or take
S boulardii or L. acidophilus reduce
risk by 47%
Other Disorders
Colds & flues – lactobacillus
plantarium DSM15312 Heal 9 ( 55%
had colds compared to 67%
in placebo group, duration
was shortened by 2 days
(Berggam, 2011)
Celiac disease – Probiotics
prevent bad bacteria
from ‘sticking’
Probiotics for babies
C section
Lactobacillus acidophilus and
Bifidobacterium infantis
31 % placebo group – diarrhea
7% Tx group
Necrotizing enterocolitis
35 died compared to 6
GI Tract Disorders
Inflammatory bowel disease –
may play a role in
decreasing postop
reoccurrence of Crohn’s
Recenti Prog Med. 2013 Apr
Better results in ulcerative
colitis
Probiotics for babies
Colic ( C section
GI system Mom should take ?
Baby Biotics randomized
trial - Ongoing using
Lactobacillus reuteri
(found in breast milk & in
many species guts, inhibits
E Coli)
Probiotics for babies
Colic
Lactobacillus reuteri DSM 17 938
(randomized trial 50 colicky
infants, crying time each
day
Pediatrics 126 (3): e526–e533
46
Probiotics for babies Toddlers
C section babies, if given antibiotics,
3 (5 years of age
or had thrush or diaper rash, or mom
had HX yeast infections
Cause of disease – not enough
friendly bacteria
Powered probiotic – 3 million
Supplement probiotics 2X / da
CFU (colony forming units) 1 – 2 X /da
Decreased colds, fevers, & use of
¼ tsp on wet finger place on
antibiotics by 62%
nipple or in baby’s mouth
Lactobacillus acidophilus
Bifidobacterium infantis

Toddlers Infant Formulas

3 (5 years of age • Mugambi. M.1

Do NOT make environment too
clean
Hand sanitizers, antibacterial
soaps incidence of allergy &
Keep immune system depressed
• Review Synbiotics, probiotics or
prebiotics in infant formula for full term
infants: a systematic review. Nutrition
Journal 2012, 11:81
• See review on my web site

Stress Probiotics
Humans
L. helveticus & B . Longum O175
psychological stress
6. Oral Health
CRP, TNF IL-6 (all go up in Promote normal flora
depression)
Antidepressants IL10 so do
Decreases oral infections
probiotics (periodontal inflammation)
Urinary cortisol after 30 days Reduces caries

47

Promote normal oral flora
TheraBreath, Aktiv(K12 (gum)
GUM Periobalance (Lozenges)
*ProBiora3 (Oragenics) mints
Improve breathe, whiten teeth
& improve sinus health
* Streptococcus: oralis, uberis, rattus –
all found in healthy mouth
Probiotics to prevent caries
• Caries are related to
imbalance of beneficial
& pathogenic bacteria
Genus: Lactobacillus,
Bifidobacterium,
Streptococcus
• Reduces # of acid forming
bacteria
Probiotics
7. Evidence(Based Guidelines
Supplements
Food
Remember:
Heat destroys probiotics in
supplements & food!!! – no hot
food or beverage 1 hour after
Probiotics – periodontal
inflammation
L. Reuteri or
Probiotic Lozenges
• Reduce levels of 3 different
pathogens that cause
periodontal disease
• Inhibits plaque formation &
gum bleeding
Probiotics for Halitosis
• Many causes:

Food, metabolic disorders,
respiratory infections

But most times imbalance of
flora in mouth

Mouthwashes or systemic
probiotics
Probiotics
• Not all probiotics are the
same!!!!
• Remember pasteurization kills
probiotics
• Look for probiotic complete
name (3) & quantity on label
• Does it have dosing & storage
instructions on label?
48
 Aug 2013 –
Probiotics 6300 Probiotics
studies
• Dependent on cells being both • Some studies promising results
viable & in sufficient # – but overall evidence is lacking
• Viability dependent on shelf live • How many & what kind: not
& passage through GI enough research
system • Guidelines for the Evaluation of Probiotics
in Food. Report London, Ontario, Canada,
• How many & what kind: not April 30-May 1, 2002. Access at
enough research ftp://ftp.fao.org/es/esn/food/wgreport2.pdf

• Packaging: dead is worthless Probiotics

• Must be alive
Fermentation:
• Never use in a bottle – heat,
light & moisture are deadly Enteric coated:
***Freeze dried (best):
• BUT if they wake up – need
food ( prebiotics Refrigerated:
• Should be in a blister pack Dark containers:
Limit sugar in the product

Probiotics Probiotics ( dosage

• What to look for on label:

Prebiotics ?

Multiple strains – more is better Forms: liquids, pills, powder???

Expiration date Good health: average dose 10 (
• What do # mean?: 15 billion/day
• should be colony(forming Illness: 20 or more billion /day
units not mg
WE need more evidence!

# of cells at manufacture – by
expiration may loose 50 – 90%

# of cells by ‘best by date’ – at least
50% remain, better # to look at

49
Probiotics ( dosage Probiotics (3/2013)
Garden of Life 85 – (32) 225 Billion
Best to take with food – dairy ($40/20 tabs)
(more food for probiotic to GNC Probiotics ultra 75 (4) 75 Billion
($25/20 tabs)
ferment) Nature’s Way (14) 35 Billion
Take long term – 2 wk on, 2 wk ($27/60 tabs)
3 in 1 Natren Health (4) 30 Billion
off
($64/60tabs)
USANA (2) 12 Billion
Consumerlab.com ($27 / 14 packets)
(**) varieties)
Many only 1 – 2 Billion

Probiotics – Supplements Probiotics – Supplements

How do I know they are Threats to taking
effective? Probiotics

After few days – chg in feces (
Antibiotics
aerodynamic missile shapes with
PPIs, H 2 inhibitors
smooth contours and little water
Preservatives, colors, additives

Less flatulence, bloating,
Lack of fiber, trans(fat
indigestion

Stress

Improvement in skin, moods

Probiotics – Supplements Probiotics – Supplements

Side effects – data is Contraindications
• Use cautious in:
lacking

Diarrhea
Premature babies

Cramps & gas
Immune deficient – HIV,
transplants

Some contain milk sugar ?
Lactose allergy???
Indwelling vascular catheters

Severe infections

Taking chemo or
immunosuppressives

50
 Probiotics - Foods Best Probiotics Foods
• Acidophilus milk Yogurt Tempeh
• Kefir Kefir Kimchee
• Yogurt must contain – Chocolate –dark Kombucha Tea
Lactobacillus bulgaricus & Microalgae (yeast)
Streptococcus thermophilus (blue-green) Sauerkraut
Home Miso soup Soft cheese
Made (gouda, Brie)
pickles

BOTTOM LINE Summary

• Need food but also Pharmacist Letter/ Prescriber Letter
supplements to really July 2012
achieve sufficient gut Product Contents; Promoted Use;
bacteria Labeled Dose or Dose Used in
Studies; Efficacy
• BUT AVOID: 14 pages
Inflammatory foods On my web site

Final Messages Final Messages

1. Gut-brain thinks differently than the CNS
2. We need to come through birth canal &
be breast fed
3. Leaky gut = leaky brain
4. Inflamed gut = inflamed brain
5. Ghrelin increases appetite & activated by
GOAT enzyme
6. To improve our diet – decrease omega
6s (inflammatory) & increase omega 3s
(anti-inflammatory).
7. Leptin, produced in white fat cells,
suppresses appetite.
8. Orexin, neurotransmitter affecting
arousal, sleep & appetite, activates
brown fat (lean fat)
9. Orexin may be next diet pill.
10. Stress increases bad bacteria &
decreases good gut bacteria.

51
 Final Messages Final Messages
11. Fat cells cause inflammation & sensitize
prefrontal cortex & limbic system
resulting in mood disorders.
12. Probiotics change gut bacteria & may
improve or treat many GI disorders. 17. Listen to your gut!!
13. Much research is still needed to
determine proper dose & type of
probiotics.
14. Just about everyone at some time in our
live can benefit from probiotics
15. To improve our diet – decrease omega
6s (inflammatory) & increase omega 3s
(anti-inflammatory).
16. Restore gut function.

52
Merrily Kuhn, PhD, ND, PhD, RN, CCRN ( r )
6748 Boston State Road
Hamburg, NY 14075

Office 716 649 1350

merrily-edsers@verizon.net
drmerrily.org

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ONLINE REFERENCES:

www.consumerlab.com : research review of good products

www.consumerlab.com/reviews/Probiotic_Supplements_Including_Lactobacillus_acidophilus_Bifidobac
terium_and_Others/probiotics/

www.fda.gov. : posts warnings on dietary supplements.

Fitbit.com Computerized recorders for steps, weight, sleep: http://www.fitbit.com/product

http://www.weilfoundation.org/home.html

information about integrative medicine and healthy lifestyles.

http://www.youtube.com/watch?v=QSTZ6AdQdwk school lunch programs: What do we feed our kids

Food, Gut & epigenetics
http://www.youtube.com/watch?v=RQbNuuIzWnA&feature=related

Is all fat the same? http://www.youtube.com/watch?v=1TtPNobccaY

Steroids & their effects on brain http://www.youtube.com/watch?v=Boy2B1oCnWs

Pre & probiotic discussion - yes it is advertising a product but it is a great discussion

http://www.youtube.com/watch?v=PEIn16Xeb-0

Decrease inflammation – check out your cleaning supplies – are they safe???
http://www.ewg.org/guides/cleaners?inlist=Y&utm_source=201303cleanersupdatefull&utm_medium=e
mail&utm_content=first-link&utm_campaign=toxics

GMO rat study - http://www.motherjones.com/tomphilpott/2012/09/gmocornrattumor

High fructose corn syrup – is it good for us??

http://www.youtube.com/watch?v=yHoIDMOB-_A (5 min)
http://www.youtube.com/watch?v=dBnniua6-oM (84 min)

LINX for GERD - https://www.youtube.com/watch?v=X4dmjT-t2oc

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Natural cures for IBS:
http://www.youtube.com/watch?v=qAFXJ7__wSI&list=PL7B410D59E8BDE37E
http://www.youtube.com/watch?v=z_S8YX6PY6s&list=PL7B410D59E8BDE37E

DAN (Defeat Autism Now)

http://www.miriamjangmd.com/DefeatAutismNow-protocol.html

Environmental toxins: http://www.safecosmetic.org ;

WWW.grinningplanet.com/2005/10-04/triclosan-article.htm
http://www.youtube.com/watch?v=pfq000AF1i8

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