The Human Microbiome in Sports Performance and Health

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Because our knowledge of the human microbiome is moving so rapidly, we turned our presentation at this conference into a discussion session so experts in the audience could share their professional knowledge and personal experience. By the end of the session, it was clear that we had barely scratched the surface of the importance of our microscopic kin to our health, to sports performance, and to how we need to think about designing research studies. A list of recommended resources is available at: www.caroltorgan.com/microbiome-sports/. We welcome your input!

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  • There's an intriguing update on the science: in slide #10 we mention that the human body contains ~10 times more microbial cells than human cells. New research suggests it's closer to a 1:1 ratio. Take a look at, "Scientists bust myth that our bodies have more bacteria than human cells" at http://www.nature.com/news/scientists-bust-myth-that-our-bodies-have-more-bacteria-than-human-cells-1.19136 and read the comments. Thank you for viewing this presentation! Carol
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  • Joshua Lederberg coined the term microbiome!
  • Joshua Lederberg coined the term microbiome!
  • Genus abundance variation box plot for the 30 most abundant genera. Insert shows phylum abundance boxplot. -B acteroides , Prevotella or Ruminococcus tended to lead the pack -Enterotype-defining genera has been linked to nutrient-processing preferences -Bacteroides to carbohydrates -Prevotella to proteins called mucins -Ruminococcus to mucins and sugars
  • The Human Microbiome in Sports Performance and Health

    1. 1. The Human MicrobiomeIn Sports Performance and HealthLawrence E. Armstrong, Ph.D., FACSMHuman Performance LaboratoryDept. of Kinesiology, University of Connecticut, Storrs, CTCarol E. Torgan, Ph.D., FACSMKinetics Consulting, Bethesda, MDTwitter: @ctorganAmerican College of Sports Medicine Annual MeetingIndianapolis, IN May, 2013
    2. 2. Goals:1.Introduce you to the human microbiome2.Provide a forum for brainstorming3.Encourage you to incorporate the human microbiomein your thinking and research4.Encourage you to think broadly about your work
    3. 3. YourCreative Ideas!Share on Twitter:#ACSMannualMtg#microbiome
    4. 4. Genetics The science of genes, heredity, and variation inliving organismsGenomics The study of genomes(all of an organism’s heredity information)DNA Sequencing The process of reading the nucleotidebases (adenine, guanine, cytosine and thymine) in DNAGWAS Genome-wide association studies
    5. 5. MicrobiomeThe community of organisms that live symbiotically inand on humans.Microbes, their genetic elements (genomes), andenvironmental interactions in a particular environment.Microbes include bacteria, fungi, protozoa and viruses.
    6. 6. The New York Times, Sunday, May 19, 2013
    7. 7. The Human Microbiome ProjectThe Human Microbiome Projectwww.commonfund.nih.gov/Hmp/www.commonfund.nih.gov/Hmp/www.genome.gov/27549144www.genome.gov/27549144
    8. 8. Human Microbiome Project (HMP) Comprehensive characterization of the humanmicrobiota and analysis of its role in human health anddisease. Data set available worldwide for use by researchers inefforts to understand and improve health. International collaboration of ~ 200 physicians,microbiologists, and laboratory scientists from~ 80 universities and scientific institutions.
    9. 9. HMP MethodsHMP Methods 242 (129 male, 113 female)242 (129 male, 113 female)healthy volunteers sampledhealthy volunteers sampledlongitudinallylongitudinally Sample 15-18 sites from:Sample 15-18 sites from:nasal passages, oral cavities,nasal passages, oral cavities,skin (behind ear, inner elbow),skin (behind ear, inner elbow),gastrointestinal tract, urogenital tractgastrointestinal tract, urogenital tract Researchers have identified > 85%Researchers have identified > 85%of all microbe genera in healthyof all microbe genera in healthyadultsadults
    10. 10. The human body contains over10 times more microbial cellsthan human cells: approximately10,000,000,000,000 (1013) cells
    11. 11.  > 10,000 microbial species in humans> 10,000 microbial species in humans ~ 1-3% of your body weight = 2-6 lb of bacteria~ 1-3% of your body weight = 2-6 lb of bacteria(your brain weighs 3 lb)(your brain weighs 3 lb) 8 million genes vs. 22 k human genes = 360 fold more8 million genes vs. 22 k human genes = 360 fold moreThe human microbiome
    12. 12.  has a biomass of 2 kg in the adult intestinal tracthas a biomass of 2 kg in the adult intestinal tract is a complex ecosystemis a complex ecosystem assists with numerous positive physiological functionsassists with numerous positive physiological functions digesting food componentsdigesting food components synthesizing vitaminssynthesizing vitamins releases a variety of metabolites involved in areleases a variety of metabolites involved in ahomeostatic balance between the microbiota and thehomeostatic balance between the microbiota and thehost (Corthier & Doré, 2010)host (Corthier & Doré, 2010)The intestinal microbiome
    13. 13. Nature 473: 2640-2644, 2011
    14. 14.  Looking for commonalities and differences betweenLooking for commonalities and differences betweengut microbiomes across different populationsgut microbiomes across different populations Combined the data from 39 individualCombined the data from 39 individualmetagenomes (n = 39 Danish, French, Italian,metagenomes (n = 39 Danish, French, Italian,Spanish, Japanese, and American)Spanish, Japanese, and American) Research is difficult: complexity of sampling, DNAResearch is difficult: complexity of sampling, DNAprep, processing, DNA sequencing, analysis.prep, processing, DNA sequencing, analysis. Physiological, nutritional, and environmentalPhysiological, nutritional, and environmentalconditions varied across individuals.conditions varied across individuals.
    15. 15. InteractiveYou are encouraged to step to the floor microphonesto introduce your creative ideas regarding futureways that we can study the microbiome as a factor inhealth, sports medicine and the exercise sciencesFormat
    16. 16. YourCreative Ideas
    17. 17. Please share your ideas!• How might the human microbiome be involvedin your area of specialization?• What experimental research designs might beemployed to test your ideas?• What practical applications do you see?
    18. 18. One ExampleScandinavian Journal of Medicine & Science in Sports22(4): 581 - 582, 2012
    19. 19. Exertional Heatstroke• elevated body temperature• tissue damage• systemic inflammation• increased intestinal permeability, especially attight junctions in the gut epithelial membrane(Dokladny et al., 2006)
    20. 20. Advanced Exertional Heatstroke:Hyperthermia with Collapse & HypotensionShock:• endotoxin• lipopolysaccharide• endotoxemiaIntestinal Epithelium
    21. 21. http://www.horseshoecrab.org/med/img/Endo.jpgBacterial cellmembrane willdegrade due toaction ofantibiotics,immune systemaction, andseverehyperthermia.This will releasepieces of themembrane intothe circulation.Gram-negative bacteria
    22. 22. http://www.horseshoecrab.org/med/img/Endo.jpgLipopolysaccharide(LPS)O-Poly-SaccharideAllows bacteriumto defend itselfagainst hostdefensesLipid A• Anchors thechain to themembrane.• Responsible fortoxicity of LPS• Treatment candecrease lethality
    23. 23. Endotoxin• Internal poison (i.e., lipopolysaccharide)• When LPS enters the blood, high concentrations maycause cardiovascular insufficiency typical of shock. Thiscondition is known as endotoxemia.
    24. 24. Exertional HeatstrokeThe extent of damage to the intestinal wall and themagnitude of endotoxin leakage into the circulation arecritical determinants of multi-organ failure and mortality.(Gathiram et al, 1981; Brock-Utne et al., 1988; Bouchama et al., 1991)
    25. 25. A Testable Hypothesis“We believe that gut bacteria represent one intrinsicmodulator of exertional heatstroke.”Why?
    26. 26. A Testable HypothesisThe intestinal microbiome (gut microrganisms):• Can be viewed as a virtual organ within an organ(O’Hara & Shanahan, 2006)• Mounting evidence indicates that these cells playa key role in illnesses/conditions such asasthma, Crohns disease, psoriasis, and obesity.
    27. 27. Exertional Heatstroke• Tissue cooling reduced intestinal permeability(Rav Acha et al., 2004)• Whole-body cooling of human exertional heatstrokepatients reduced circulating levels of• LPS• TNFα• Interleukin-1α(Bouchama et al., 1991)This supports the widely-recognized therapy of coldwater immersion as the treatment of choice(Casa et al., 2007)
    28. 28. Exertional Heatstroke• Prophylactic administration of LPS antibodies (anti-LPS)reduced morbidity and mortality in primates with extremehyperthermia (Gathiram et al., 1987)• The above facts implicate the gut as a major factor in theetiology of exertional heatstroke.
    29. 29. Exertional Heatstroke• Animal research suggests that the intestinal microbiomeis more plastic than previously anticipated (Manichanh etal., 2011). This suggests that the human microbiome maybe selectively remodeled, with bacterial transplants orspecialty pharmaconutrients such as glutamine orneuropeptides (O’Hara & Kudsk, 2000).• Probiotics may someday be selectively prescribed toenhance intestinal barrier function (Brand & Reinecker,2002) or specific anti-inflammatory effects (Galdeano &Perdignon, 2006), prior to intense or prolonged exercise inhot environments.
    30. 30. YourCreative Ideas
    31. 31. Please share your ideas!• How might the human microbiome beinvolved in your area of specialization?• What experimental research designsmight be employed to test your ideas?• What practical applications do you see?
    32. 32. Beetroot juice and exercise performance
    33. 33. Methods“Subjects were instructed to keep a food andphysical activity diary …. to arrive at thelaboratory in a rested and fully hydrated statefollowing an overnight fast, and to avoidstrenuous activity in the 24 h preceding eachtesting session. …”
    34. 34. And….“… to abstain from using antibacterialmouthwash and chewing gum throughoutthe study because these are known toeradicate the oral bacteria that arenecessary for the conversion of nitrate tonitrite.”
    35. 35. Inorganic nitrate (NO3-)nitrite (NO2-)nitrogen oxides, such as nitric oxide (NO)Physiological changesHumans don’t have theenzyme for this step.Bacteria on the back ofour tongues do this for us.Beetroot juice journey
    36. 36. YourCreative Ideas
    37. 37. Please share your ideas!• How might the human microbiome beinvolved in your area of specialization?• What experimental research designsmight be employed to test your ideas?What controls are needed?• What practical applications do you see?
    38. 38. The Skin MicrobiomeSkin = 1.8 m2ofmicrobial real estateBlue circles:sebaceous or oilyGreen circles: moist(typically skin creases)Red circles:dry, flat surfacesThe skin microbiome. Nat Rev Microbiol.Grice EA, Segre JA. 2011 Apr;9(4):244-53.
    39. 39. The Skin MicrobiomeCan be affected by:• Lotions, soaps,cosmetics• Temperature, humidity• Contact with othersThe skin microbiome. Nat Rev Microbiol.Grice EA, Segre JA. 2011 Apr;9(4):244-53.
    40. 40. • Teammates share distinct skin microbial communities• Opposing teams’ bacterial communities convergedduring the course of a roller derby bout• The human skin microbiome shifts in compositionduring activities involving human to human contact• Contact sports provide an ideal setting in which toevaluate dispersal of microorganisms between people
    41. 41. Parents who clean their baby’spacifier by sucking on it mayreduce that child’s allergiesin later life.
    42. 42. YourCreative Ideas
    43. 43. Please share your ideas!• How might the human microbiome beinvolved in your area of specialization?• What experimental research designsmight be employed to test your ideas?• What practical applications do you see?
    44. 44. The microbiome interacts withthe intestinal epithelium:• direct contact• metabolic products• fragments of cell wall (LPS)
    45. 45. The intestinalmicrobiota plays arole in thedevelopment of thehost’s innate andadaptive immuneresponsesEur. J. Clinical Nutrition (2002), 56, suppl 3, S60-64
    46. 46. Complex interactions between bacteria,the gut, and tissue immune systems couldbe a prerequisite for metabolic disease.
    47. 47. Enterotypes of the human gut microbiome.Arumugam et al. Nature 473: 2640-2644, 2011
    48. 48. Previous studiessuggest that gutbacteria mayinfluence behavior.This research in micesuggests that gutbacteria may influencea wide variety of brainand psychiatricdisorders, such asdepression, autism,and schizophrenia.Science News, Oct. 8, 2011, pg 9
    49. 49. Nature Reviews. Endocrinology 7: 639-646, 2011• A number of studies describe characteristic differences between thecomposition and/or activity of the gut microbiota of lean individuals andthose with obesity.• Although these data are controversial, they suggest that specificphyla, classes or species of bacteria, or bacterial metabolic activitiescould be beneficial or detrimental to patients with obesity.• The gut microbiota is, therefore, a potential nutritional andpharmacological target in the management of obesity and obesity-related disorders.
    50. 50. A relationship between gut flora metabolism andCVD pathogenesis may aid development ofnovel diagnostic tests and therapeutic approachesfor atherosclerotic heart disease.
    51. 51. YourCreative Ideas
    52. 52. Please share your ideas!• How might the human microbiome beinvolved in your area of specialization?• What experimental research designsmight be employed to test your ideas?• What practical applications do you see?
    53. 53. Factors that may influence the microbiome: Antibiotic use Birth (vaginal vs. caesarian) Diet (food and supplements) Hygiene (mouthwash, lotions, sanitizers) Built environment (materials, cleaning) Social environment (family, friends, teammates, pets) Physical environment (altitude, heat, spaceflight) What else?
    54. 54. The microbiome and theInternational Space Station (ISS)microBEnetwww.microbe.net/project-iss-microbiome-collaboration-with-science-cheerleadersAlso see:NASAhttp://www.nasa.gov/mission_pages/station/research/experiments/1010.htmlJ. Craig Venter Institutehttp://www.jcvi.org/cms/research/projects/astronaut-microbiome/
    55. 55. Using the microbiome for diagnostics: Bacterial biomarkers Determine risk /susceptibility for conditions Diagnose conditions before clinical symptomsappear (heart disease, Parkinsons??) Diagnose over-training? What else?
    56. 56. Using the microbiome for treatments:Fecal Microbiota Transplants (FMT) “Infusion of a fecal suspension from a healthyindividual into the gastrointestinal tract of an individualwith colonic disease.” Used to treat C. difficile colitis (bowel inflammation) Goal: re-establish normal intestinal compositionDiseases = altered / imbalanced microbial compositionT. J. Borody, J. Campbell, Gastroenterol Clin N Am 41, p 781-803, 2012
    57. 57. Fecal Microbiota Transplants (FMT)Procedure Donor history (similar to blood donation) Obtain stool sample, homogenize with saline, filter Administer: Nasogastric tube Enema Colonoscope Perform within 6-24 hours of obtaining sample Future: frozen samples, lyophilized powder (capsules?)T. J. Borody, J. Campbell, Gastroenterol Clin N Am 41, p 781-803, 2012
    58. 58. Fecal Microbiota Transplants (FMT)As of May 2013 the FDA requiresInvestigational New Drug (IND) application(Because FMT meet the definition of a biologic therapy)
    59. 59. Ethical, legal, social issues:Should probiotic mixes designed to manipulate themicrobiome be regulated?Should you take samples of your microbiome whenyou are healthy and store them, so you can repopulateyour communities if you get sick?Will this change what it means to be ‘human’?
    60. 60. Could the microbiomebe used as an ergogenic aid?Instead of blood doping,could there be bacterial doping?(metabolism, over-training, travel)
    61. 61. Athlete Biological Passport“The fundamental principle of the AthleteBiological Passport is based on the monitoringof selected biological parameters over timethat will indirectly reveal the effects of dopingrather than attempting to detect the dopingsubstance itself.”- World Anti-Doping Agency (WADA)www.wada-ama.org/en/Science-Medicine/Athlete-Biological-Passport/Will this become theAthlete MicroBiological Passport?
    62. 62. µBiomehttp://ubiome.com/DIY Science (Citizen science)American Gut Projecthttp://humanfoodproject.com/americangut/
    63. 63. Your FinalIdeas
    64. 64. Please continue our conversation …Share comments and ideasFollow the buzz on Twitter: #microbiomeList of recommended references available at:www.caroltorgan.com/microbiome-sports/Thank you for participating!

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