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 â Applied Nutrition
National Institute of Nutrition, Hyderabad
Fourth National Certificate Course on Hospital Infection Control
September 2016
B. Ravinder Reddy
3. âą Introduction
âą Evolution of Microbiome
Human Microbiome
A New Clinical Frontier
âą Evolution of Microbiome
âą Role of Microbiome in Health
âą Role of Microbiome in Diseases
âą Therapeutic Manipulation of Microbiome
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):463â471
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 â 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 âve
B. Ravinder Reddy
Firmicutes
Clostridium G+ve
Proteobacteria
Rare Phyla: Cyanobacteria, Fusobacteria, etc.
E coli, etc G âve
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
15. Microbes Shaped Our Evolution
B. Ravinder Reddy
Michael Shapiro. Gut Microbiota and Host Evolution â 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 â 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 â 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
22. Healthy Effects of Microbiota
B. Ravinder Reddy
The gut microbiota â 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 â 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
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
33. Urinary
Excretion
< 0.5 mg/d
Portal venous return
> 95% biliary secretion
Biliary secretion (pool x cycles)
(3 g x 4 â 12 cycles) = 12 â 36 g
Synthesis
0.2 â 0.6 g/d
Bile Acid Metabolism
Fecal excretion
0.2 â 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
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
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
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
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