1. 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

2. Speaker Disclosure Cleveland HeartLab-Speaker and consultant
Pure Encapsulations-Speaker and consultant
Exact Sciences-Speaker
EpigeneticsRX-Speaker and consultant

3. 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

4. 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

6. 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 pp
ever discovered

7. 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:
Science 2009: Vol. 326 no pp

8. 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:

9. Major Influences On The Microbiome
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

10. 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):e

11. 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

12. Functions Of The Gut Microbiome
Protection against invading pathogenic bacteria-barrier 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

13. Altered Microbiota And Disease Risk Associations: Those Already Known!
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)

14. 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 Jan;59(1):172-81

15. 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):

16. 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: pro-inflammatory organism, and other enteric pathogens
Long term adherence to high protein, low fermentable carbohydrate/fiber “weight-loss” diets increase Bacteroides and lower Firmicutes-likely increasing risk of colonic disease
De Filippo et al. Impact of diet in shaping gut microbiota. Proc Natl Acad Sci USA 2010; 107:

17. Source: Aliment Pharmacol Ther 2015 Blackwell Publishing

18. Dybiosis Of Gut Microbiota Theory
Accounts for the 3 Defining Components of PCOS:
Anovulation/menstrual irregularity
Hyperandrogenism: acne, hirsutism, alopecia
Multiple small ovarian cysts
Tremellen K et al, Med Hypotheses.(2012) Jul;79(1):

19. 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

20. 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

22. Thoughts On How To Build A Better Microbiome
Prebiotics-Fermentable “fertilizer” for the microbiome
Mostly soluble fibers-fructans :
inulin, lactulose, galacto-oligosaccharides
Fermented by bacteria living in colon to
produce short-chain fatty acids, which provide
nutrition for cells lining gut
Thought to reproduce some of the benefits of
natural high-fiber diets-some studies show
benefit for insulin resistance

23. 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

24. 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:

26. Functional Medicine Approach to Healing the Gut: The Four R’s
Heal The Gut!
Functional Medicine Approach to Healing the Gut: The Four R’s
Remove
Repair
Replace
Re-inoculate

27. The Future 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

28. Thank You! Felice L. Gersh, MD
My unique protocols to restore gut health and improve the microbiome are available by ing me!