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.

2. 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

3. 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

4. THE HUMAN
MICROBIOME
The Human Microbiome: The
Undiscovered Country

5. 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

7. 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

8. 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

9. 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)

10. 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?

11. What factors determine the species composition of
normal flora in the human body?

12. Skin regions are like geographic regions of Earth

13. HOW MANY DIFFERENT ORGANISMS
ARE NORMALLY IN OUR BODY?
• Mouth ; > 600 Species
• Skin : > 600 Species
• Intestine : (Cecum/ colon) : 8,000
genera
• Vagina : > 200 Species

14. 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

15. 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.

16. Yes
How?
No
Why ?

17. • 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)

22. 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

23. THE CONCEPT OF A CORE
MICROBIOME

24. 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

25. Let’s focus on the microbial community in the gut:
How is the community assembled?
How does community composition affect function?

26. 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

27. Where are all the organisms?
O’Hara and Shanahan (2006) EMBO Reports

28. THE HUMAN GUT FLORA
DiBiase, et al. Mayo Clin Proc 2008;83:460-469

29. When Microbes entered in the
humans body?
Is it starts in the Mother’s
Womb?
Or? after the birth ?

30. 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

32. Lina.et,al 2012
Primary Succesion in the
The gut environment selects its microbiota

33. MATURATION OF THE MICROBIOME
DURING THE 1ST YEAR OF LIFE
Development of the Human Infant Intestinal Microbiota
Palmer C,Bik EM,DiGiulio DB,Relman

34. 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

35. 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

36. 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

37. GUT FLORA AND THE BRAIN
Collins and Bercik in GASTRO 2009;136:2003–2014

38. Fecal Microbiota Transplants
(FMT)

39.  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.

40. 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.

41. 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?

42. 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..??

43. • 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.

44. 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

45. 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.

46. 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!