Transcript the microbiome - PCOS Conferences

THE MICROBIOME:
Exploring New Paradigms In Our
Understanding Of PCOS
Felice L. Gersh, M.D.
Medical Director
Integrative Medical Group of Irvine
Faculty Reviewer
Integrative Medicine Fellowship
University of Arizona School of Medicine
Speaker Disclosure
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Cleveland HeartLab-Speaker and consultant
Pure Encapsulations-Speaker and consultant
Exact Sciences-Speaker
EpigeneticsRX-Speaker and consultant
Lecture Objectives
• Understand what the gut microbiome is, how it
develops, and its enormous significance to the
health of the individual it resides in
• Learn how an unhealthy gut microbiome can
have dramatic effects on the function of women
and lead to the creation of systemic
inflammation, insulin resistance, weight gain,
hyperandrogenemia, and ovulatory dysfunction
(PCOS!)
• Acquire basic knowledge on what steps one can
take to restore a healthy gut microbiome
New Concepts In What It
Means To Be Human
• DNA sequencing has redefined what it actually
means to be human
• The gut microbiome impacts every aspect of our
being: digestion, metabolism, neurological,
psychological functions, reproductive systems,
and immune system
• Our “modern” lifestyle has dramatically impacted
our microbiome
• There are ways to modify the damage to our
microbiomes
The Microbiota Of The Gut:
Concept Of The Super-Organism
• Humans are home to vast numbers of microbial
organisms-a complex ecosystem of several
hundred bacterial species
• Dominant human bacterial phyla: Bacteroidetes,
Firmicutes, Actinobacteria, Proteobacteria
• Microbes outnumber our own cells 10:1
• Total microbiota-greater than 100 trillion!
• The human gut microbiome is the most complex
ecosystem ever discovered
Science 2009: Vol. 326 no. 5960 pp. 1694-169
The Normal Microbiota:
Concepts Of The Super-Organism
• The richness of the biodiversity is critical to the
health of the host organism
• An individual has a unique microbial
composition: a microbial “fingerprint.”
• Microbiome contains 150 times as many genes
as our human genome
• Microbes-1000 grams in GI tract
• For each individual-the microbiota are fairly stable,
though some species are transient: major changes with
increase aging, BMI, host genotype and immunologic,
antibiotics, diet, and exercise
Albenbert LG, et al. Diet and the intestinal microbiome. Gastroenterology 2014; 146: 1564-72
Science 2009: Vol. 326 no. 5960 pp. 1694-169
The Composition Of
The Human Microbiome
• Viruses: acellular
• Pro-caryotes: have no nucleus
Archaea (strict anaerobes)-originally thought to be
commensals or aid digestion-may be involved in
GI and oral disorders
• Bacteria: aerobes and anaerobes
• Eukaryotes: have a nucleus and organelles
Micro-fungi (yeasts)
Protozoa
Helminths (parasitic worms)
Kim BS et al. Current status and future promise of the human microbiome. Pediatr Gastroenterol Hepatol Nutr.
(2013);16:71-79
Eckburg PB et al. Diversity of the human intestinal microbial flora. Science(2005);308:1635-1638
Major Influences On The Microbiome
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Genotype of host
Type of birth
Excessive Hygiene
Diet: macronutrients, fiber, phytochemicals,
alcohol
• Probiotics and prebiotics
• Medications: Antibiotics, NASAIDs, OCPs,
Hormones, etc.
• Stress (emotional, social)
Plos One. 2011;6(12):e2828
Development Of The Microbiome
• The intra-uterine environment during pregnancy is
not sterile! Initial inoculum starts there.
• Vaginal delivery exposes baby to the vaginal
microbiome
• Cesarean Section - baby is exposed to
predominant bacterial species of the mother’s skin
flora and of the hospital attendants: Increases the
baby’s risk of allergies, asthma, Celiac Disease,
Type 1 diabetes, IBD
• Breast feeding provides bacteria from the mother’s
GI tact!!
Plos Biol, 2013, Vol 11(8):e1001631
Functions Of The Microbiome
• Energy expenditure, satiety, and glucose homeostasis
• In contact with the second largest (after brain) neural
pool of cells in the body
• Connects with largest group of immune cells in our
bodies- maturation of the immune system in infancy,
maintenance of its homeostasis during life- development
of the nervous system and cognitive function
• Modulation of systemic immunity-inflammatory and
autoimmune disease protection: Bifidobacterium,
Bacteroides, Clostridium, Lactobacillus
The Good Gut, J. and E. Sonnenberg, Penguin Press 2015
Functions Of The Gut Microbiome
• Protection against invading pathogenic bacteriabarrier against invading foodborne pathogens
• Detoxification and biotransformation (hormones,
toxins)
• Digestion and energy collection-fermentation of
non-digestible dietary components- main product
SCFAs which interact with intestinal microbiota
and host cells
• Synthesis of key substances: SCFAs, amino acids,
neurotransmitters, vitamins
Altered Microbiota And Disease Risk
Associations: Those Already Known!
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Colorectal Cancer
GI infections-Clostridium Difficile
Cardiovascular Disease
Inflammatory Bowel Disease
Irritable Bowel Syndrome
Fatty Liver Disease
Obesity and Metabolic Syndrome
Autoimmune Diseases and Degenerative
Processes
• Allergies
Zhang, H. et al. Dynamics of Gut Microbiota in Autoimmun Lupus. Applied and
Environmental Microbiology 80.24(2014)7551-560
Metabolic Endotoxemia
• Cell walls of gram negative bacteria contain
compounds called lipopolysaccharides
(endotoxins)
• When the integrity of the gut lining is
compromised, these toxic substances can leak
through the gut lining and enter the bloodstream
Mehta, NN et al. Experimental endotoxemia induces adipose inflammation.Diabetes. 2010 Jan;59(1):172-81
Metabolic Endotoxemia
• The immune system recognizes these foreign
molecules and mounts an attack against them,
resulting in systemic inflammation
• This inflammation can result in insulin
resistance, leptin resistance (leading to obesity),
depression, muscle pain, and fatty liver disease
• When the level of endotoxin in the blood
increases two to three times normal, the
condition is known as metabolic endotoxemia
Kelly CJ et al. The Health Consequences of Dietary Endotoxemia. Nutrition in Clinical Practice. 2012;27(2):215-225
A “Western” Diet And The Microbiome
• Western style diets are high in fat/sugar, low in
fiber-decrease beneficial Firmicutes that
metabolize dietary plant-derived
polysaccharides to SCFAs and increase
mucosa-associated Proteobacteria: proinflammatory organism, and other enteric
pathogens
• Long term adherence to high protein, low
fermentable carbohydrate/fiber “weight-loss”
diets increase Bacteroides and lower Firmicuteslikely increasing risk of colonic disease
De Filippo et al. Impact of diet in shaping gut microbiota. Proc Natl Acad Sci USA 2010; 107:14691-6
Source: Aliment Pharmacol Ther 2015 Blackwell Publishing
Dybiosis Of Gut Microbiota Theory
Accounts for the 3 Defining Components
of PCOS:
1. Anovulation/menstrual irregularity
2. Hyperandrogenism: acne, hirsutism,
alopecia
3. Multiple small ovarian cysts
Tremellen K et al, Med Hypotheses.(2012) Jul;79(1):104-112
Dysbiosis Of Gut Microbiota Theory
• Poor diet and other influences create
disturbances in bowel bacterial flora
• An increase in gut mucosal permeability
develops
• The result is an increase in the passage of
lipopolysaccharides (LPS) from Gram negative
colonic bacteria into the systemic circulation
Dysbiosis of Gut Microbiota Theory
• This results in the activation of the immune
system-with increased production of
inflammatory cytokines
• The inflammatory cytokines interfere with insulin
receptor function-the reduced insulin sensitivity
drives up insulin levels
• Increased serum insulin levels increase ovarian
production of androgens and interferes with
normal follicle development
Thoughts On How To Build
A Better Microbiome
Prebiotics-Fermentable “fertilizer” for the microbiome
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Mostly soluble fibers-fructans :
inulin, lactulose, galacto-oligosaccharides
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Fermented by bacteria living in colon to
produce short-chain fatty acids, which provide
nutrition for cells lining gut
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Thought to reproduce some of the benefits of
natural high-fiber diets-some studies show
benefit for insulin resistance
Thoughts On How To Build
A Better Microbiome
Probiotics: Live micro-organisms administered in
sufficient quantity-benefit health
• May benefit obesity and can lower cholesterol
• May produce antimicrobial compounds, keeping
out harmful bacteria by competing for nutrients
Contra-biotics: Soluble fiber which can block
attachment of adherent and invasive bacteria to
the bowel mucosa
Martin HM et al. Enhanced E coli adherence. Gastroenterology 2004;127:80-93
Thoughts On How To Build
A Better Microbiome
• Dietary composition, modification, and
interventions have a marked impact on gut
microbiota diversity
• Plant based fiber is critical in influencing the
composition and metabolic activity of the
microbiome and determining levels of short
chain fatty acids (SCFAs)-which are important
for intestinal health
• Agrarian diets high in fruit/legume fiber are
associated with greater microbial diversity
Lattimer JM et al. Effects of dietary fiber and its components on metabolic health. Nutrients 2010; 2: 1266-89
Heal The Gut!
Functional Medicine Approach to
Healing the Gut: The Four R’s
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Remove
Repair
Replace
Re-inoculate
The Future
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Personalized probiotics
Prebiotics and Contrabiotics
Narrow spectrum antibiotics
Nutrition-organic, real, whole foods
Nutraceuticals
Change in contraception
Management of circadian rhythms
Management of stress
Understanding of epigenetic effects on PCOS
Solauri, E. et al. Role of Probiotics in Reducing the Risk of Gestational Diabetes. Diabetes Obes Metab Diabetes, Obesity and
Metabolism(2015)
Yarbrough, V.L. et al. Antimicrobial Peptides in the Female Reprod. Tract. Human Reproduction Update 21.3(2014):353-77
Thank You!
Felice L. Gersh, MD
My unique protocols to restore gut health and
improve the microbiome are available by
emailing me!
[email protected]
www.integrativemgi.com