Human Microbiome - An Evolving Clinical Frontier
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The evolving role of Human Microbiome in health and disease Dr. B Ravinder Reddy Hyderabad, India
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Human Microbiome - An Evolving Clinical Frontier
- 1. B. Ravinder Reddy MS, FRCS (Edinburgh), FRCS (Glasgow) Gastrointestinal Surgeon Human Microbiome A New Clinical Frontier Gastrointestinal Surgeon Care Hospital, Banjara Hills, Hyderabad Honorary Professor – Applied Nutrition National Institute of Nutrition, Hyderabad Fourth National Certificate Course on Hospital Infection Control September 2016 B. Ravinder Reddy
- 2. Hospital Acquired Infections B. Ravinder Reddy
- 3. • Introduction • Evolution of Microbiome Human Microbiome A New Clinical Frontier • Evolution of Microbiome • Role of Microbiome in Health • Role of Microbiome in Diseases • Therapeutic Manipulation of Microbiome B. Ravinder Reddy
- 4. Knowing the Human Microbiome B. Ravinder Reddy
- 5. Human Microbiome A New Clinical Frontier Introduction B. Ravinder Reddy
- 6. Human Cells: 37.2 Trillion; Human Genes: 21000 B. Ravinder Reddy Bianconi E. An estimation of the number of cells in the human body. Annals of Human Biology. 2013;40(6):463–471 Alison Abbott. Nature News January 2016 . doi:10.1038/nature.2016.19136
- 7. Microorganisms: 40 Trillion; Genes: > 3 Million B. Ravinder Reddy Structure, function, diversity of healthy human microbiome. NATURE June 2012
- 8. Cells Outnumbered by 1:3 Genes Outnumbered by 1:300 70 kg Person 2.2 kg Present Everywhere B. Ravinder Reddy 2.2 kg Microbiota Metabolism Equals that of Liver
- 9. Discovered 340 years ago – 50 Phyla Are Known Humans contain < 10 phyla (average about six phyla) B. Ravinder Reddy Taxonomic variations. Nature Review Genetics 2012;13:260 - 270 Data from 250 healthy individuals Each point represents one microbial community from one body site on one person (Knight Lab)
- 10. Human Microbiome Common Phyla Actinobacteria Bifidobacterium G+ve Bacteroidetes Bacteroides G –ve B. Ravinder Reddy Firmicutes Clostridium G+ve Proteobacteria Rare Phyla: Cyanobacteria, Fusobacteria, etc. E coli, etc G –ve
- 11. Human Microbiome Common & Rare Phyla B. Ravinder Reddy Taxonomic variations. Nature Review Genetics 2012;13:260 - 270
- 12. Skin Microbiota Murray PR, Rosenthal KS, Human Microbiome in Health & Disease Medical Microbiology 8th Edition, 2016B. Ravinder Reddy
- 13. Different Sites Different Phyla & Species B. Ravinder Reddy Taxonomic variations. Nature Review Genetics 2012;13:260 - 270
- 14. Human Microbiome A New Clinical Frontier Evolution B. Ravinder Reddy
- 15. Microbes Shaped Our Evolution B. Ravinder Reddy Michael Shapiro. Gut Microbiota and Host Evolution – Scaling Up Symbiosis Trends in Ecology & Evolution. 2016; 31(7): 539-549
- 16. Evolution of Human Microbiome - Factors B. Ravinder Reddy Cho I, Blaser MJ. The Human Microbiome. Goldman-Cecil Medicine 25th Edition, 2016
- 17. Factors affecting microbiota - birth to adulthood Breast-fed Formula-fed Solid food Healthy Healthy Malnutrition Antibiotic exposure Obese Elderly 65 – 80 yrs Elderly 100 + yrs Cho I, Blaser MJ. The Human Microbiome. Goldman-Cecil Medicine 25th Edition, 2016 B. Ravinder Reddy Firmicutes Bacteroidetes Actinobacteria Proteobacteria Others Unborn Baby Toddler Adult Elderly
- 18. Predictors of skin microbiota B. Ravinder Reddy Structure and function of the human skin microbiome. Trends in Microbiology. December 2013, Vol. 21, No: 12
- 19. Factors affecting microbiota - birth to adulthood Maternal Prenatal - Environmental - Antibiotics - Diet - Illness - Epigenetics - Delivery – ND vs. CS - Cutaneous contact - Breast feeds - Bottle feeds - Iatrogenic exposures Neonate Newborn Cho I, Blaser MJ. The Human Microbiome. Goldman-Cecil Medicine 25th Edition, 2016 B. Ravinder Reddy
- 20. Factors affecting microbiota - birth to adulthood Early Childhood - Exposure to new strains - High community-instability - Rapid increase in diversity - Response to diet - Illness & development Adult Life Cho I, Blaser MJ. The Human Microbiome. Goldman-Cecil Medicine 25th Edition, 2016 - Differentiated microbiota - Community stability - Slow rate of change - Susceptible to diet - Illness, senescence B. Ravinder Reddy
- 21. Human Microbiome A New Clinical Frontier Health Effects B. Ravinder Reddy
- 22. Healthy Effects of Microbiota B. Ravinder Reddy The gut microbiota – masters of host development and physiology Nature Reviews Microbiology 2013
- 23. Microbiota helps in maturation of GIT Reduced Mucus Thickness Altered Mucus Properties Microbiota Increases Mucus B. Ravinder Reddy The gut microbiota – masters of host development and physiology Nature Reviews Microbiology 2013 Reduced AMP & IgA Increased AMP, IgA & Tolerance
- 24. Microbiota: Protect from Intestinal Infections Murray PR, Rosenthal KS, et al. Human Microbiome in Health & Disease Medical Microbiology 8th Edition, 2016 B. Ravinder Reddy I. Microbiota, II. Mucus Layer, III. Epithelium
- 25. Other benign bacteria Mucus layer inner Fecalibacterium PrausnitziFiber F. prausnitz and/of absent fiber Opportunist microbes, toxins Disrupted Microbiome & Reduced mucus layer Mucus layer outer B. Ravinder Reddy Scientific American. March 2015 Resident Peacekeeper
- 26. Gut-Brain Axis B. Ravinder Reddy
- 27. CNS, SNS, PNS Intestinal Lumen MicrobiotaMicrobiota Diet Water, Vitamins, Electrolytes Nutrients & Metabolites Toxins. MAMPs: Infection Cellular Organization of Neuroimmune Interactions in the GIT Trends in Immunology. 2016 B. Ravinder Reddy
- 28. Various Genomes Vs Metabolic Functions in Human Gut Human Bacteria Achaea B. Ravinder Reddy Human Microbiome Project: Structure, function and diversity of the healthy human microbiome. Nature 2012, 486:207-214
- 29. Microbiota Plays a Significant Role in Immunity B. Ravinder Reddy Human Microbiome in Health & Disease. Medical Microbiology 8th Edition, 2016 Protects From Infectious Diseases
- 30. Microbiota Can Protect From Acute & Chronic Skin Diseases Dynamics of skin microbiome interactions B. Ravinder Reddy Structure and function of the human skin microbiome. Trends in Microbiology. December 2013, Vol. 21, No: 12
- 31. Production of Short Chain Fatty Acids B. Ravinder Reddy Lumen Outer Mucin Layer Inner Mucin Layer Gut Mucosa Acetate Butyrate Propionate B Ravinder Reddy. Noncaloric Benefits of Carbohydrates. The Importance of Nutrition as an Integral Part of Disease Management. Karger Publications©2015. ISBN 978-3-318-05499-6.
- 32. Microbiota Maintains Gastrointestinal Integrity B. Ravinder Reddy Human Microbiome in Health & Disease. Medical Microbiology 8th Edition, 2016
- 33. Urinary Excretion < 0.5 mg/d Portal venous return > 95% biliary secretion Biliary secretion (pool x cycles) (3 g x 4 – 12 cycles) = 12 – 36 g Synthesis 0.2 – 0.6 g/d Bile Acid Metabolism Fecal excretion 0.2 – 0.6 g/d Primary BA Intestinal Bacteria Secondary BA B. Ravinder Reddy Secondary BA Protects: Clostridium infections Human Microbiome in Health & Disease. Medical Microbiology 8th Edition, 2016
- 34. Benefits of MACROBIOTA Baracktrema Obamai Food allergies Autoimmune diseases B. Ravinder Reddy Baracktrema Obamai Human Microbiome in Health & Disease. Medical Microbiology 8th Edition, 2016
- 35. Human Microbiome A New Clinical Frontier Diseases Caused B. Ravinder Reddy
- 36. Adipose tissue Increased TG Increased inflammation Liver Increased inflammation Brain Increased satiety Altered fermentation Increased energy harvest Altered Microbiota B. Ravinder Reddy Epithelium Increased permeability Reduced PYY, GLP-1 Increased inflammation Muscle Reduced fatty acid oxidation Increase in NCD Human Microbiome in Health & Disease. Medical Microbiology 8th Edition, 2016
- 37. Liver-Gut Axis Dysregulated Bile Acids Diseases Liver Hepatitis A, B, C Alcoholic hepatitis Alcoholic fatty liver Non-alcoholic fatty liver Non-alcoholic steatohepatitis Primary & secondary cirrhosis Malignant tumours of the liver Altered Physiology Liver Hepatitis A, B, C Alcoholic hepatitis Alcoholic fatty liver Non-alcoholic fatty liver Non-alcoholic steatohepatitis Primary & secondary cirrhosis Effects on Altered Microbiome Dysbiosis Malignant tumours of the liverPrimary & secondary cirrhosis Malignant tumours of the liver Implications of microbiota and bile acids in liver injury and regeneration. Journal of Hepatology 2015 (6) 1502 - 1510 Intestines Inflammation Immune activation Intestinal dysmotility Bacterial overgrowth Intestinal permeability Bacterial translocation Intestines Ileitis Gastroenteritis Ischemic colitis Short bowel syndrome Ischemic bowel disease Irritable bowel syndrome Inflammatory bowel disease B. Ravinder Reddy
- 38. Effects on Altered Microbiome in Women B. Ravinder Reddy
- 39. Lifestyle Diet Hygiene Hyperimmunity - IL – 6 Immunodeficiency - NOD2 Antibiotics Altered intestinal Effects on Altered Microbiome & Conditions Metabolic dysfunction - IL – 6 - IL – 12 - TNF - NOD2 - IL – 10 Metabolic dysfunction Altered intestinal microbiota The gut microbiota – masters of host development and physiology. Nature Reviews Microbiology 2013 B. Ravinder Reddy
- 40. Inflammation Inflammatory Bowel Disease Cancer, Diabetes Summary slide B. Ravinder Reddy
- 41. Human Microbiome & Obesity 12 obese unrelated adults on FAT-R or CARB-R low calorie diets B. Ravinder Reddy
- 42. Human Microbiome & CVD Carnitine Wang et al Nature 2011 Tang, Wang NEJM 2013 B. Ravinder Reddy
- 43. TMAO alters cholesterol metabolism - multiple compartments Koeth et al. Nature Medicine 2013 B. Ravinder Reddy
- 44. Fat, bile and gut microbes Dietary fat can alter bile composition and so favour the growth of pro-inflammatory gut microbes. Peter J Turnbaugh. NATURE Volume 487 July 2012 B. Ravinder Reddy
- 45. Smoking Alcohol Exercise Lifestyle Diet Xenometabolites High Fat & Low Fiber High Protein High Choline Medications NSAIDS Etc Microbiome & Cancer Promotion B. Ravinder Reddy Bile Acids Phyto- chemicals Choline Metab Fiber SCFA Altered Microbiome Dysbiosis Inflammation B. fragilis E. faecalis E. coli Cancer Polyps Oncogenic Promotion Immuno- senescence
- 46. Host Genetics Host Microbiome Microbiome & Cancer Promotion Innate Immunity Phagocytosis Autophagy Increased in Enterobacteria Species, etc B. Ravinder Reddy Inflammation Ulceration/Fibrosis Metaplasia Cancer
- 47. Gut Bacteria Impaired microvilli function Altered Microbiome in Critical Illness B. Ravinder Reddy Systemic Spread Bacterial Overgrowth Blood Vessel Gut Microbiota in Health and Disease . Physiology Reviews 2010
- 48. StressLeaky Gut Blood Vessel Altered Microbiome in Critical Illness B. Ravinder Reddy Gut Bacteria Red Blood Cells Gut Microbiota in Health and Disease . Physiology Reviews 2010
- 49. Persistent InflammationDysbiosis Altered Microbiome NAFLD Energy (SCFAs) Firmicutes Fatty Liver Implications of microbiota and bile acids in liver injury and regeneration. Journal of Hepatology 2015 (6) 1502 - 1510B. Ravinder Reddy Disregulated Bile Acids Choline/TMA Pathway • Cirrhosis • HCC
- 50. Potential Consequences of NAFLD Cancers B. Ravinder Reddy Implications of microbiota and bile acids in liver injury and regeneration. Journal of Hepatology 2015 (6) 1502 - 1510
- 51. Altered Skin Microbiome in Necrotising Infections Lactobacillus Streptococcus pyogenes Lipoteichoic acid Lactic Acid B. Ravinder Reddy Destroys Lipoteichoic Acid Gut Microbiota in Health and Disease . Physiology Reviews 2010
- 52. Immune System Intestinal Diseases Effects on Altered Microbiome Jun Wang. The Human Microbiome & Personalized Medicine Genomics and Personalized Medicine. 2009. Chapter 14, 166 - 172 Obesity, Diabetes (T2) CVD, Cancer, Liver & Autoimmune Diseases Development of resistance to antibiotics B. Ravinder Reddy
- 53. Role of Microbiome in Diseases Diseases of all systems & B. Ravinder Reddy Most organs Gut Microbiota in Health and Disease . Physiology Reviews 2010
- 54. Human Microbiome A New Clinical Frontier Manipulation B. Ravinder Reddy
- 55. Therapy By Manipulation of Microbiome Probiotics B. Ravinder Reddy Gut Microbiota in Health and Disease . Physiology Reviews 2010
- 56. Therapy By Manipulation of Microbiome Fecal Microbial Transplant B. Ravinder Reddy
- 57. Therapy By Manipulation of Microbiome Fecal Microbial Transplant B. Ravinder Reddy Bojanova DP, Bordenstein SR . Fecal Transplants: What Is Being Transferred?. PLoS Biol 14(7): 2016
- 58. Therapy By Fecal Microbial Transplant Clostridium difficile infections Hospital acquired infections Infections due to multi drug resistant organisms B. Ravinder Reddy The Human Microbiota Novel Targets for Hospital Acquired Infections & Antibiotic resistance Annals of Epidemiology 2016 (26) 342 - 347
- 59. Fecal Composition & Transplant What is being transferred? B. Ravinder Reddy Bojanova DP, Bordenstein SR . Fecal Transplants: What Is Being Transferred?. PLoS Biol 14(7): 2016
- 60. Human Microbiome A New Clinical Frontier Summary B. Ravinder Reddy
- 62. Individualised & VariesIndividualised & VariesIndividualised & VariesIndividualised & Varies
- 63. Essential for healthy development,Essential for healthy development, metabolism & immunitymetabolism & immunity
- 64. Influenced byInfluenced by diet, exercise & medicationsdiet, exercise & medications
- 65. Deviation can cause diseases:Deviation can cause diseases: infectious & noninfectious & non--infectiousinfectious
- 66. Microbial transplant & probioticsMicrobial transplant & probiotics is promising in many diseasesis promising in many diseases
- 68. Further Reading Nutrition Workshop Series Vol. 82 Published Date October 2015 B. Ravinder Reddy
- 70. VenkiVenkiVenkiVenki RamakrishnanRamakrishnanRamakrishnanRamakrishnan, President, President, President, President More than ever, science must beMore than ever, science must beMore than ever, science must beMore than ever, science must be central to all our lives!central to all our lives!central to all our lives!central to all our lives! VenkiVenkiVenkiVenki RamakrishnanRamakrishnanRamakrishnanRamakrishnan, President, President, President, President
- 71. g{tÇ~ lÉâg{tÇ~ lÉâg{tÇ~ lÉâg{tÇ~ lÉâ dr.bravinder.reddy@carehospitals.com www.drbravinderreddy.com