THE HUMAN GUT MICROBIOME—FACT AND FICTION · The Gut Microbiome – Bacteria (~99%) ~100 trillion...
Transcript of THE HUMAN GUT MICROBIOME—FACT AND FICTION · The Gut Microbiome – Bacteria (~99%) ~100 trillion...
THE HUMAN GUT MICROBIOME—FACT AND FICTIONDr. Gabrielle Fundaro, CISSN, CHC
Renaissance Periodization Nutrition Coach
Overview
■ Introduction to the Gut Microbiome
■ Lifestyle and the Microbiome
■ Myth-Busting and Practical Application
INTRODUCTION TO THE MICROBIOME
■ 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%
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
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)
Functions of the Gut Microbiome
(Andoh, 2018)
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
Defining Diversity■ Taxonomic Diversity
– Richness: # of species– Evenness: representation– Phylogeny: relatedness
■ Functional Diversity– Metabolomics, proteomics,
transcriptonomics
(El-Ashram, 2017)
Defining Diversity■ Diversity
– Richness: # of species– Evenness: representation– Phylogeny: relatedness
■ Functionality– Metabolomics, proteomics,
transcriptonomics
(El-Ashram, 2017)
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
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)
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
Gut Health and Dysbiosis
OBESITY
COLORECTAL CANCER
INFLAMMATORY BOWEL DISEASES
Dysbiosis?Variability even occurs within a single disease
state!
Adapted from: Duvallet, 2017
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
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
Vertebrates cause pollution.
LIFESTYLE AND THE MICROBIOME
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.
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)
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/
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
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
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
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)
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)
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
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!
MICROBIOME MYTHS AND PRACTICAL APPLICATIONS
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
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.
“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
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)
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
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
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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