The storyline behind the modern epidemic of inflammation driven disease goes as follows: • Chronic degenerative conditions (Diseases of Civilization – DOCs) are on the rise and have overtaken infections as the major source of death and illness. • This epidemiological transition is due, at least in part, to environmental changes that have increased the disease liability of genetic profiles that were previously benign. • These DOCs are associated with increased systemic inflammation stemming from inappropriate stressor-response mechanisms. • Much of this inflammation is generated and/or perpetuated by the gut-brain axis. • Gut-brain axis derived inflammation leads to disruptions in psycho-neuro-immunological (PNI) balances. • Pathophysiological mediators of PNI disturbances can be measured and treated. • A cornerstone of said treatment is the regular consumption of a high quality multi-strain probiotic. The carefully selected strains in Tri-Flora have been shown to: • Decrease pro-inflammatory cytokines; • Increase anti-inflammatory cytokine IL-10; • Stimulate regulatory immune cells; • Inhibit immune response to LPS (lipopolysaccharide) transduction; • Improve intestinal barrier function; • Enhance mucosal and systemic immune responses; • Produce and deliver neurotransmitters such as GABA and serotonin. And in so doing accomplish some very intriguing clinical feats: 1. Lessen symptoms of chronic fatigue syndrome; 2. Act as an adjunct to standard care in the treatment of Major Depressive Disorder; 3. Improve anxiety and reduce brain cell death; and 4. Help women lose weight. It is for reasons such as this, that my most commonly recommended supplement for most people is a high quality probiotic. Tri-Flora by IP Formulas is my new favorite.

1. Microbes For
Mental Health

2. The Global Epidemic Of
Inflammatory
Disorders,
Including
Mental Illness,
is Holding The
World Captive.

3. Unifying Theory of Diseases
of Civilization: Short Version
INFLAMMATION
“Leaky
Gut”
Diet,
Toxins &
Other
Stressors
Genetic
Suscepti-
bility &
ELA*
* ELA – Early Life Adversity

4. So What?
Glad You Asked.
Inflammation
Causes Unique
Imbalances In Your
Hormones,
Neurotransmitters,
Immunity, and
Growth Factors.

5. For Instance…

6. The Study of
which is called
Psycho-Neuro-
Immunology
(PNI).

7. Psycho-Neuro-
Immunology
Defined
“Psychoneuroimmunology is a convergence of
disciplines – namely, the behavioral sciences, the
neurosciences, endocrinology, and immunology –
intended to achieve a more complete understanding
of the way the interactions among these systems
serve homeostatic ends and influence health and
disease.” -Robert Ader

8. Nervous
System
Immune
System
Endocrine
System
Stressor
Cytokines
Hormones
Anxiety
Depression
Insomnia
Thyroid
Adrenal
Gonadal
Inflammation
Infections
Allergies
Pain
PNI In
Action

9. Or, If You
Prefer…

10. SO, WHAT
ABOUT
THE MY GUT
BUGS?

11. The microbes that first inhabit your gastrointestinal
tract (from birth and shortly thereafter) establish for
the rest of life your so called “Stress Set Point” (SSP)
and ultimately the PNI imbalances that stress will
elicit.

12. For Those of You Who
Think I Make This
Stuff Up:
(I’m not that smart.)

13. Early Life And The Gut
Th, T-helper; Treg, regulatory T-cells.
Sudo N et al. J Physiol. 2004;558(Pt 1):263-275.
Negative early life experiences alter initial gut
colonization that predisposes an individual to
stress-induced inflammation later in life by:
• Altering one’s HPA-axis set point;
• Increasing intestinal permeability;
• Decreasing mucosal immune tolerance
by shifting Th0 cell differentiation from
Treg to Th1 or Th2 effector cells
In essence, early life experiences,
through modification of the gut
ecology, magnify stressors, amplify
the stress response, and inhibit
corrective homeostatic mechanisms
resulting in chronic sustained
inflammation.
Not an
actual
gut bug.

14. Melancholic Microbes:
A Link Between Gut
Microbiota and Depression?
• “There is a growing awareness of the potential for
microbiota to influence gut-brain communication in
health and disease. “
• “Intriguingly alterations in microbiota composition is
being demonstrated across a variety of models of
chronic stress and depression.”
Melancholic microbes: a link between gut microbiota and depression?
Dinan TG, Cryan JF. Neurogastroenterol Motil. 2013 Sep;25(9):713-9.

15. • External or internal stressors trigger increased production
of pro-inflammatory cytokines;
• Various trigger factors for depression may compromise
the intestinal barrier (“Leaky Gut”), induce LPS
(lipopolysaccharide – fragments of bacterial/viral cell
walls) translocation. Increased blood LPS not only
causes a systemic inflammation but also a central
neuroinflammation and a long-standing activation of brain
cytokines and microglia.
• Thus, LPS translocation may induce sickness behavior
and vegetative symptoms of major depression.
Maes M. Neuro Endocrinol Lett. 2008 Jun;29(3):287-91.
Inflammation, Oxidative Stress, Leaky
Gut, and Depression

16. Major depressive disorder: probiotics may be an adjuvant therapy. Logan AC, Katzman M. Med Hypotheses. 2005;64(3):533-8.
Psychobiotics: a novel class of psychotropic. Dinan TG, Stanton C, Cryan JF. Biol Psychiatry. 2013 Nov 15;74(10):720-6.
• Probiotics have the potential to lower systemic inflammatory cytokines,
decrease oxidative stress, and improve nutritional status.
• The effect of probiotics on systemic inflammatory cytokines and oxidative
stress may ultimately lead to increased brain derived neurotrophic factor
(BDNF).
• Such probiotics produce and deliver neurotransmitters such as gamma-
aminobutyric acid (GABA) and serotonin, which act on the brain-gut axis.
• Studies in rodents suggests that certain probiotics alleviate symptoms of
depression and anxiety. Evidence also suggests these probiotics can
lessen the symptoms of chronic fatigue syndrome.
• “It is our contention that probiotics may be an
adjuvant to standard care in MDD [Major
Depressive Disorder].”
Probiotics: A Data
Supported Treatment

17. Probiotic Blend Containing 5 Billion Live
Organisms:
Saccharomyces boulardii ......... 125 mg
Lactobacillus acidophilus Rosell-52
(reclassified L. helveticus)
Lactobacillus rhamnosus Rosell-11
Bifidobacterium longum Rosell-175
60 capsules per bottle
One Capsule Contains:
IP Proudly Announces Our
Newest Probiotic Blend

18. Probiotic Blend Containing 5 Billion Live
Organisms:
Saccharomyces boulardii ......... 125 mg
Lactobacillus acidophilus Rosell-52
(reclassified L. helveticus)
Lactobacillus rhamnosus Rosell-11
Bifidobacterium longum Rosell-175
60 capsules per bottle
One Capsule Contains:
With Carefully Selected
Probiotic Strains:
Lactobacillus helveticus &
Bifidobacterium longum

19. How We Select
Strains: The Research Literature
• A probiotic formulation (Lactobacillus helveticus and
Bifidobacterium longum) improved anxiety and reduced
brain cell death in the emotional centers in animal models
of depression.
• Researchers observed that pretreatment with probiotics
attenuated the HPA axis and autonomic nervous system
(ANS) response to stress and restored TJ integrity (“leaky
gut”).
• Investigators concluded that this probiotic combination, by
modulation of gut microbiota, has beneficial effects on brain
activity during stress.
Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice.
Ait-Belgnaoui A, Colom A, Braniste V, Ramalho L, Marrot A, Cartier C, Houdeau E, Theodorou V,
Tompkins T. Neurogastroenterol Motil. 2013 Dec 30.

20. Probiotic Blend Containing 5 Billion Live
Organisms:
Saccharomyces boulardii ......... 125 mg
Lactobacillus acidophilus Rosell-52
(reclassified L. helveticus)
Lactobacillus rhamnosus Rosell-11
Bifidobacterium longum Rosell-175
60 capsules per bottle
One Capsule Contains:
And Lactobacillus rhamnosus,
which in a recent study was
shown to:
• Help women lose weight;
• By possibly altering intestinal
permeability, and thereby
• Keeping proinflammatory molecules from
entering the bloodstream
Effect of Lactobacillus rhamnosus
CGMCC1.3724 supplementation on weight loss
and maintenance in obese men and women.
Sanchez M, Darimont C, Drapeau V, Emady-
Azar S, Lepage M, Rezzonico E, Ngom-Bru C,
Berger B, Philippe L, Ammon-Zuffrey C, Leone
P, Chevrier G, St-Amand E, Marette A, Doré J,
Tremblay A.
Br J Nutr. 2013 Dec 3:1-13.

21. Probiotic Blend Containing 5 Billion Live
Organisms:
Saccharomyces boulardii ......... 125 mg
Lactobacillus acidophilus Rosell-52
(reclassified L. helveticus)
Lactobacillus rhamnosus Rosell-11
Bifidobacterium longum Rosell-175
60 capsules per bottle
One Capsule Contains:
Lastly, Saccharomyces boulardii
for good measure

22. We Put Saccharomyces boulardii
in Tri-Flora because it:
Decreases pro-inflammatory
cytokines (IL-8, IL-6, IL-1β,
TNFα, IFNγ).
Increases anti-inflammatory
cytokine IL-10.
Interferes with NF-κB
mediated signaling in
immune and colonic epithelial
cells.
Blocks activation of ERK1/2
and MAP kinases
Stimulates production of
PPAR-γ.
Enhances mucosal immune
response and sIgA levels.
Stimulates Treg cells.
Inhibits DC-induced
activation of T effector cells.
Enhances systemic immune
response and levels of serum
IgG to C. difficile toxins A&B.
Inhibits immune response to
LPS.
Improves barrier function.
Kelesidis T, Pothoulakis C. Therap Adv Gastroenterol. 2012 Mar;5(2):111-25
Thomas S, Przesdzing I, Metzke D, Schmitz J, Radbruch A, Baumgart DC. Clin Exp Immunol. 2009
Apr;156(1):78-87

23. “In this case, taking a
probiotic supplement is
definitely advised. While I
do not generally advocate
taking a lot of supplements,
a high quality probiotic is an
exception.”
Dr. Mercola Has Been Preaching the
Good Word on Gut Bugs For Years

24. Keep Your Gut Bugs Happy:
Try Tri-Flora
• Integrative Psychiatry, Inc.
• info@integrativepsychiatry
• Integrativepsychiatry.net
• (800) 385-7863