Human Microbiome

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Human Microbiome is the current project in Research field. The importance of Microorganisms in the human body, the importance and novel roe of the microorganisms on a human body is very effective and helpful. Fecal Transplantation is a unique and helpful technique to cure a dreadful disease naturally by means of microorganisms or introducing the normal flora in to the body again.

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Human Microbiome

  1. 1. OUTLINE OF TALK  What is meant by Human Microbiome  Describe the factors and processes that influence community assembly and composition  Importance of Human microbiome  Gut Microbiota and its importance  Clostridium difficile  Fecal Transplantation  Conclusion
  2. 2. Goal of my Talk • To make you all generally conversant in the language of microbiomes and metagenomics • To provide examples of how microbial communities affect health and cure diseases • To give practical examples of how medical interventions interact with the microbiome and change outcomes
  3. 3. THE HUMAN MICROBIOME The Human Microbiome: The Undiscovered Country
  4. 4. What is the Human Microbiome Microbe : Tiny living organism, such as bacterium, fungus, protozoan, or virus Microbiome : Collectively all the microbes in the human body; a community of microbes Biofilm : A community of microbes that live together on a surface A metagenome: the collection of genes/genomes in an environmental
  5. 5. The Problem : Who am I Vs. Who are we The Human Genome Project started in 1990 Provides a basis to understand how the human genome relates to health and disease However, the number of microbial cells is 10 times more than human cells in a human being
  6. 6. MICROBES ARE ALL OVER US There are millions of microbes per square inch on your body Thousands of different species on the skin alone some thrive on dry patches of the elbow, others thrive in moist environment of armpit It is estimated that there are more microbes in your intestine there are human cells in your body
  7. 7. Sites that harbor a normal flora: Skin and mucous membranes Upper respiratory tract Gastrointestinal tract Outer opening of urethra External genitalia Vagina External ear canal External eye (lids, conjunctiva)
  8. 8. We are Covered with Microbes ? How dense they are? External Ear Nose Who are they? Sinuses Where did they come from? Eyes Mouth Do they all matter? Pharynx Democracy? Dictatorship? Skin Socialism Enteric tract Can they be moved? Vagina Transplanted? Adjusted? Do they change when I am sick? When they change do they make me sick?
  9. 9. What factors determine the species composition of normal flora in the human body?
  10. 10. Skin regions are like geographic regions of Earth
  11. 11. HOW MANY DIFFERENT ORGANISMS ARE NORMALLY IN OUR BODY? • Mouth ; > 600 Species • Skin : > 600 Species • Intestine : (Cecum/ colon) : 8,000 genera • Vagina : > 200 Species
  12. 12. A microbe’s view of us Skin Bacterial cells outnumber your body cells 10:1 and comprise up to 4-6 lbs of your body mass
  13. 13. Benefits of the normal flora 1. Synthesize and excrete vitamins Vitamin K and Vitamin B12 2. Prevent colonization by pathogens competing for attachment sites or for essential nutrients 3. May antagonize other bacteria the production of substances which inhibit or kill non-indigenous species(nonspecific fatty acids, peroxides, bacteriocins). 4. Stimulate the development of certain tissues i.e., intestines, certain lymphatic tissues, capillary density 5. Stimulate the production of cross-reactive antibodies. Low levels of antibodies produced against components of the normal flora are known to cross react with certain related pathogens, and thereby prevent infection or invasion.
  14. 14. Yes How? No Why ?
  15. 15. • Microbes can communicate each other by chemical language • They interact each other by signals and respond to the signals by using chemical language • This Phenomenon is called “ Quorum Sensing” • Quorum Sensing signals are called auto inducers • All auto inducers are chemical language signals to one another. • Quorum Sensing is a system of stimulus and response correlated to population density. Many species of bacteria use quorum sensing to coordinate gene expression according to the density of their local population .(wiki)
  16. 16. GOALS OF THE HUMAN MICROBIOME PROJECT • Determine if there are sets of microbes common to each human • Understand if changes in our microbiota result in different states of health or disease • Develop new technologies for studying complex microbial and studying complex microbial systems within their natural environments • •Begin to deal with the legal ethical and social complications that may arise with human microbiome
  17. 17. THE CONCEPT OF A CORE MICROBIOME
  18. 18. WHAT DO THE MICROBES DO FOR US? • Provide the ability to harvest nutrients and • Produce additional energy otherwise inaccessible to the host. • Produce vitamins • Metabolize xenobiotics • Provide resistance to tumor and cancer leading neoplasms • Assist in developing a mature immune system
  19. 19. Let’s focus on the microbial community in the gut: How is the community assembled? How does community composition affect function?
  20. 20. INTESTINAL MICROBIOME • >1,000 species but most in adults are from 2 phyla: Firmicutes and Bacteroidetes • Outnumber human somatic cells by factor of 102 • Total Weight: 1-2 kg • 60% of total fecal content • Concentration: ~1012/gram in colon • •Total #: ~1014
  21. 21. Where are all the organisms? O’Hara and Shanahan (2006) EMBO Reports
  22. 22. THE HUMAN GUT FLORA DiBiase, et al. Mayo Clin Proc 2008;83:460-469
  23. 23. When Microbes entered in the humans body? Is it starts in the Mother’s Womb? Or? after the birth ?
  24. 24. THE MICROBIOME: WHO’S THERE? • Early gut colonization has four phases • Phase 1: Sterile gut • Phase 2: Initial acquisition: vagina, feces, hospital • Phase 3: Breast feeding or bottle-feeding (different) • Breast fed more bifidobacteria (up to 90% of flora) • Bottle fed more diverse; more Bacteroides , and Clostridial species • Phase 4: Start of solids; move to adult flora • Bifidobacteria remain key flora into adulthood Ley, Peterson, Gordon. Cell 2006 ;124:837 Ley, et al. PNAS. 2005, 102: 11070 Edwards, et al. Br J Nutr. 2002
  25. 25. Lina.et,al 2012 Primary Succesion in the The gut environment selects its microbiota
  26. 26. MATURATION OF THE MICROBIOME DURING THE 1ST YEAR OF LIFE Development of the Human Infant Intestinal Microbiota Palmer C,Bik EM,DiGiulio DB,Relman
  27. 27. THE MICROBIOME: WHO’S THERE? • Adult Microbiome: − Increasing diversity of flora as we age − In some newer PCR (16S rRNA) studies, up to 92% of the flora in adults were “novel” species • Serial stool collections show remarkable stability by an individual − Greatest concordance with twins − Less concordance with households − Host genetic influence unexplored. McCartney and Gibson in Gastrointestinal Microbiology, 51-73, 2006
  28. 28. METABOLOMICS • Study of the metabolites and small molecules that the body and gut bacteria produce. • New area of science • Broader than proteomics • Includes bacteria products with our own genetic products • Pioneered by Jeremy Nicholson and Jeff Gordon
  29. 29. GUT FLORA AND METABOLISM • Microbial genomes enhance our metabolic activity • May indirectly or directly effect our metabolism • The colon is very active metabolically • 20-70 gms of carbons and 5-20 gms of protein/day • Over 100 kcal per day! • Mass of colonic microbiome = single kidney • Metabolically as active as the liver Hooper, et al. Annu Rev Nutr, 2002
  30. 30. GUT FLORA AND THE BRAIN Collins and Bercik in GASTRO 2009;136:2003–2014
  31. 31. Fecal Microbiota Transplants (FMT)
  32. 32.  Clostridium difficile also known as "CDF/cdf", or "C. diff", is a species of Gram-positive spore-forming bacterium that is best known for causing antibiotic-associated diarrhea(AAD).  While it can be a minor normal component of colonic flora, the bacterium is thought to cause disease when competing bacteria in the gut have been wiped out by antibiotic treatment.  In severe cases, C. difficile can cause "pseudomembranous colitis," a severe inflammation of the colon.
  33. 33. Inflammation  Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants  The classical signs of acute inflammation are pain, heat, redness, swelling, and loss of function. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process.
  34. 34. LITTLE-KNOWN FECAL TRANSPLANT CURES WOMAN'S BACTERIAL INFECTION “After surviving a near-fatal car accident, Kaitlin Hunter found herself battling a devastating bacterial infection in her colon that also threatened her life. The persistent infection was beaten through a little-known technique involving the transplant of fecal matter from Hunter's mother... Following the July procedure, "I've been so happy," said Hunter, 20, of Marietta, Georgia. "I'm cured." Why did this work? What happened in Katie’s colon?
  35. 35. Procedure: FMT TJ.BOOD ET.AL  Donar History (Similar to blood donation ) Obtain stool sample, homogenize with saline and filter  How to Administer  Nasogastric Tube  Enema  Colonoscope  Perform 6-24 hrs of obtaining the sample  Future: Frozen Samples, Lyophilized Powders, Capsules..??
  36. 36. • Fecal microbiota transplantation (FMT) also known as a stool transplant is the process of transplantation of fecal bacteria from a healthy individual into a recipient. It has been proven to be a highly effective treatment for patients suffering from Clostridium difficile infection (CDI), which produces effects ranging from diarrhea to pseudomembranous colitis.
  37. 37. BACTERIOTHERAPY Clostridium difficile-associated diarrhea (CDAD) - usually results from prior antibiotic treatment and persistant disruption of gut microbiota - can be severe, even causing death J Clin Gastroenterology (2010) 44:354-360
  38. 38. CONCLUSIONS • The human microbiome and the Microbiome Project: research just beginning… • Gut flora by their genes, by-products, and metabolic activity influence our metabolism, weight, activity, immunity, health and disease. • Manipulation of gut flora may be an integral part of weight loss programs and different disease treatments in the future.
  39. 39. CONCLUSIONS • Future studies must focus on the mechanisms that influence of our gut flora. • Studies must be place to controlled and high quality research should be done. • Truly need translational science to work at the levels of the petri dish, genomics, and clinical outcomes. • Hope much much more to come!

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