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THE HUMAN GUT MICROBIOME—FACT AND FICTIONDr. Gabrielle Fundaro, CISSN, CHC
Renaissance Periodization Nutrition Coach
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Overview
■ Introduction to the Gut Microbiome
■ Lifestyle and the Microbiome
■ Myth-Busting and Practical Application
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INTRODUCTION TO THE MICROBIOME
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■ All animals harbor microbiomes and microbiota– Genetic material and microorganisms– Oral, Skin, Vaginal, Intestinal (Gut), Fecal
■ The Gut Microbiome– Bacteria (~99%)■ ~100 trillion bacteria with 1000’s species
and millions of genes– Archaea■ Methanogens
– Fungi and Protists■ Saccharomyces, Candida
– Viruses■ Non-living human and bacterial pathogens
(bacteriophages)
Defining the Microbiome
50%
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Supplements
Diet & Physical Activity
Species, Location, Ethnicity, Age, Gender
Forming the Gut Microbiome■ 1/3 human-species specific■ 2/3 individual
– Birth and Early Diet■ Vaginal/C-Section■ Breast/Bottle
– Location and Ethnicity■ African/African American
– Age■ 0-3, 3-12, 12-60, 60+
– Gender– Disease State
■ IBD, T2D– Diet– Physical Activity– Cohabitation?– Cleanliness?
Hierarchy of Influence on Diversity
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Factors Influencing Microbial Profile
§ Acidity§ Oxygen availability§ Nutrient availability§ Structure
§ Numbers and diversity increase from stomach to large intestine
§ Luminal, mucosal, and fecal populations differ significantly
§ Bacteria may be luminal or loosely or tightly associated with the intestinal cells (mucosal)
(Jobin, 2015 & Neufeld, 2011)
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Functions of the Gut Microbiome
(Andoh, 2018)
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Functions of the Gut Microbiome
Escheria Genus Canis
Escheria coli Species Canis lupus
Nissle O104:H4 Shiga-toxin
Sub-Species (Strain)
Canis lupus familiaris
(dog)
Canis lupus dingo
(dingo)
§ Within a species, specific strains have variable functions§ E. coli Nissile is a
beneficial probiotic§ E. coli O104:H4 causes
food-borne illness§ Dogs love babies§ Dingoes eat babies
§ BUT, strains can be lost/gained without a change in gut function
§ AND low-abundance strains may have HUGE functional effects
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Defining Diversity■ Taxonomic Diversity
– Richness: # of species– Evenness: representation– Phylogeny: relatedness
■ Functional Diversity– Metabolomics, proteomics,
transcriptonomics
(El-Ashram, 2017)
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Defining Diversity■ Diversity
– Richness: # of species– Evenness: representation– Phylogeny: relatedness
■ Functionality– Metabolomics, proteomics,
transcriptonomics
(El-Ashram, 2017)
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Consider the Entire System and Limitations■ Taxonomic diversity does not directly
indicate functional diversity– Important to consider
methanogens and under-represented taxa
– Genetic redundancy is beneficial and allows for taxonomic change without loss of function
■ View the microbiome as a complex ecosystem rather than a collection of discrete microbes
■ Consider limitations of sample site, methods of identification, and host species
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Gut Health and Dysbiosis§ No definition or specific profile of
healthy or unhealthy microbial profile§ Healthy controls cluster by
geographic location
§ “Healthy”§ Stability due to diversity§ Resistant to perturbations
(Nam, 2011)
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Gut Health and Dysbiosis§ No definition or specific profile of
healthy or unhealthy microbial profile
§ “Dysbiosis”§ Common characteristics of GI and
metabolic diseases§ Lack of diversity§ Intestinal permeability &
inflammation§ Metabolic endotoxemia
§ Elevated levels of plasma endotoxin (LPS) leading to chronic lo inflammation
Suzuki, 2012
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Gut Health and Dysbiosis
OBESITY
COLORECTAL CANCER
INFLAMMATORY BOWEL DISEASES
Dysbiosis?Variability even occurs within a single disease
state!
Adapted from: Duvallet, 2017
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Dysbiosis: Cause or Consequence?§ Rodent fecal microbiome
transplants (FMT) illustrate a microbiome-disease link
§ Method of replicating human disease states and responses to dietary interventions
§ Increased energy harvesting & appetite
§ Behavioral changes§ Inflammatory responses
§ Approaches ‘cause-effect’§ BUT, significant limitations
for applicability to humans
Aliosio, 2016
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Adapted from: https://www.frontiersin.org/files/Articles/82367/fendo-05-00047-HTML-r1/image_m/fendo-05-00047-g001.jpg
Gut Health and Dysbiosis
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Vertebrates cause pollution.
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LIFESTYLE AND THE MICROBIOME
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Key Note in Human
Intervention Studies
Individual differences have a much stronger effect than diet or physical activity.
Greater microbial diversity is negatively correlated with diet-induced or exercise-induced changes.
What does this mean?
A more diverse microbiome is a more resilientmicrobiome. Short-term interventions cannot mitigate the effects of long-term habits.
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Core Microbiota Remain Stable Over Time and May Influence Response to Interventions§ Microbiomes ‘cluster’ based on
predominant taxa1) P: Japan, South Africa, Sweden2) B: Australia, Canada, Chile, Italy3) F: Poland
§ After 3 weeks on HCLF or LCHF, clusters remained stable § Specific changes to certain
taxa§ Differed significantly based on
cluster
(Morrison, 2019)
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Carbohydrates and Fiber
§ Dietary plant diversity correlates with gut microbial diversity in humans
§ Digestible carbohydrates (simple sugars and starches) are primarily used by the host§ Further research needed for effects of
digestible carbohydrate
§ Indigestible carbohydrates (fiber and resistant starch) pass through to large intestine where they are fermented§ Soluble (readily fermentable) and insoluble
(bulk-forming)§ Production of gases and short-chain fatty acids§ pH regulation§ Bacterial & colonocyte fuel sources
https://selfhacked.com/blog/butyrate-health-benefits-butyrate-derivatives-sodium-butyrate-phenylbutyrate-trybutyrine-butyric-acid-butyrate-prodrugs-butyrate-producing-bacteria/
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ProteinProtein intake correlates with diversity & improved body composition in physically-active humans
§ In the presence of sufficient fiber
§ Differing fatty acid, amino acid, and fiber content
§ Differing potential for lean/fat mass gain in mice
§ Low-fiber, high-protein diets may increase mucin-degraders and reduce diversity
§ Metabolites may influence health & disease§ Production of TMAO from carnitine is
microbiome-dependent§ Tryptophan -> indole. serotonin § BCAA’s -> barrier function
Singh, 2017 & Willing, 2019
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Fats
Cell Metabolism 2015 22, 658-668DOI: (10.1016/j.cmet.2015.07.026)
HFD (>40% kcal) reduces diversity in rodents & humans§ Low in fiber and high in protein§ Bifidobacteria < Bacteroides§ Reduced butyrate
§ Usually high in sat fat§ Firmicutes : Bacteroidetes ratio shift § Intestinal permeability & increased circulating
endotoxin§ Metabolic endotoxemia
Fat source may affect microbiome (secondarily to total fat content)§ Saturated fat > protein in sedentary humans§ Omega-3 may reduce inflammation§ Rodent FMT reduced adiposity on lard-based diet
Caesar, 2015
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Cardiovascular Fitness and Physical Activity Correlate with Diversity
Cardiovascular fitness may explain 15-20% of diversity in sedentary and recreationally active adults
Higher levels of fitness and physical activity associated with increased butyrate-producing bacteria and
fermentative efficiency(Estaki, 2018 & Bressa, 2017)
More fit, more diverse
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Cardiovascular Fitness and Physical Activity Correlate with SCFA Production
Microbiota of elite athletes contains higher levels of specific genera & genes associated with lactate fermentation to
propionate
Higher levels of fitness and physical activity associated with increased butyrate production
(Estaki, 2018 & Scheiman, 2019)
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Habitual Diet & Exercise Interactions■ Athletes’ diets are higher in protein, carbohydrates, and energy
– Diets may be lower in fiber and FODMAPs– May enrich bile-tolerant taxa and/or butyrate-producers
(Estaki, 2018)
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Habitual Diet & Exercise Interactions
Protein intake is negatively correlated with diversity in distance-runners on a low-fiber diet.
Total fat intake is negatively correlated with Bifidoabundance in bodybuilders on a low-fiber diet.
(Park, 2019)
■ Sport-specific diets vary greatly in relative macronutrient contribution– Increased fat intake à reduced carbohydrate intake à loss of beneficial microbes
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Improved Metabolic Health & Performance
Enhanced SCFA
Availability and Lactate Clearance
Enhanced Fermentative
Capacity
Diet & PAL
Clostridiales
Veillonella
Prevotella
Akkermansia
Roseburia
Faecalibacterium
m. Smithii
(archaea)
(Mailing, 2019)
Appetite regulationInsulin sensitivitypH modulationCell proliferationTight junction proteinsColonocyte energy source
“Gut health!”
Not fully realized during low-carb, high-fat diets or
low fiber intake!
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MICROBIOME MYTHS AND PRACTICAL APPLICATIONS
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Don’t fall for the fecal fallacies!
Diagnosing or curing dysbiosis
Diagnosing or curing leaky gut
Healing the gut Rebuilding or designing a healthy
biome
Dysbiosis as a cause for weight gain
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What about the gut health ‘superfoods’?Fermented and Cultured Dairy
Fermented Vegetables, Grains, and Meats
Probiotics Digestive Enzymes
Glutamine Collagen and Bone
Broth
“Detoxes”
Dishonorable Mention: IgG Antibody food sensitivity
testing, MRT/LEAP testing, GI MAP testing, OAT, etc.
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“Broad-spectrum” probiotics?Problem Probiotic
Diarrhea--prevention (antibiotic or traveler’s)
Diarrhea--treatment (pediatric)
S. boulardii, L. casei, L. acidophilus
L. rhamnosus GG, S. boulardiiIBS--treatment B. infantis, L. plantarum, L. rhamnosus, B. breve
IBD—treatment VSL-#3
Upper respiratory tract infection—prevention/treatment
L.casei Shirota, L. gasseri, B. longum, B. bifidum, B. animalis lactis
Diet-induced insulin resistance and dyslipidemia--prevention
Weak evidence—VSL-#3, L. casei, B. infantis, cultured dairy beverages
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Probiotics for performance?Probiotics do not improve exercise performance or
recovery
• No effect in endurance athletes, team sports, or laboratory time trials
• Conflicting results in strength and markers of inflammation and soreness• Increased torque
production & reduced soreness unreplicated
Probiotics may improve GI distress in males
• Worsened effects in females
• Reduced duration but not severity
• Reduction in fecal zonulin unreplicated
Probiotics may reduce URTI incidence
• Reduced duration, severity, and frequency of upper respiratory tract infections some studies
• Reductions in some inflammatory markers (TNF-a, CRP, IL-6, Eppstein-Barr antibodies)
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Gastric distress is common in athletes!■ Physical activity appears to promote ‘gut health,’ but…
■ 20-60% of athletes report exercise-related gastric distress– Cramping, nausea, diarrhea■ Impaired nutrient utilization■ Performance impediment
■ Most prevalent in endurance athletes and females– Heat and psychological stress– Intensities >80% VO2max– Hyperthermia, lack of blood flow, pH changes, free radicals, mechanical stress
■ Changes in intestinal permeability lead to increased circulating endotoxin– Commonly associated with GI distress
■ Athletes who ingest insufficient fiber with high protein intake may not fully realize beneficial effects of exercise on the microbiome
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GI Distress Prevention
Carbohydrate-containing beverages may reduce markers of intestinal permeability
6-8% carbohydrate concentration•Glucose, glucose + fructose,
maltodextrin
Reducing FODMAP intake before/during exercise
Fructose, lactose, soluble fibers•Fruit, dairy, whole grains,
legumes, veggies
Limiting fat intake before/during exercise
Slows gastric emptyingMCT oil increases gastric distress
Avoiding intense exercise close to a meal GET usually 1-4 hours
Avoiding extreme endurance exercise in the heat
Consistent pattern of increased endotoxin levels in extreme endurance athletes
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Practical Applications for Health
Emphasize
Plants and their fibers (especially soluble)
Omega-3 fats (fish, walnuts, flax, chia)
Plant-based & lean proteins
Regular physical activity and recovery
Limit
Dietary fats to <40% calories
Saturated fat to <10% calories
High-fat red meat and processed meat products
Only certain foods as needed (allergies &
intolerancesProbiotics:
Strain-specific effects
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