This presentation include microbiome involve in human health and disease. classification and categorization of microbiota is aslo given.Anatomical area in which these microbes present.

1. Human Microbiome in Health and Disease
Shivanshu Bajaj
M.Pharmacy (Pharmacology)
SPER , Jamia Hamdard

2. CONTENT
1) Introduction
2) Categorization of microbiota
3) Human microbiome project
4) Analytical techniques
5) Classification of microbiome
6) Anatomical areas
7) Role of microbiome in human health
8) Role of microbiome in human diseases
9) References

3. INTRODUCTION
The human microbiota/microbiome is the aggregate of microorganisms
that resides on or within any of a number of human tissues and biofluids
It includes –
Skin Mammary glands
Placenta Seminal fluid
Uterus Ovarian follicles
Lung Saliva
Oral mucosa Conjunctiva
Biliary gland Gastrointestinal tracts.

4.  Microbiota include bacteria, archaea, fungi, protists and viruses.
 Though micro-animals can also live on the human body, they are
typically excluded from this definition.
 The human microbiome refers specifically to the collective genomes of
resident microorganisms.
Categorization of Microbiome-
1. Commensal – they co-exist without harming the host
2. Mutualistic – both host and microbe are benefited
3. Non-pathogenic – they harm the host by producing metabolites. For ex :-
metabolites produced, like trimethylamine, which the human body
converts to trimethylamine N-oxide via FMO3-mediated oxidation

6. Relative numbers-
In 2014, the American Academy of Microbiology published that approximately 37.2
trillion microbial cell, meaning that the ratio of microbial-to-human cells, if the
original estimate of 100 trillion bacterial cell, is closer to 3:1
Human Microbiome Project –
The Human Microbiome Project (HMP) was a United States National Institutes of
Health (NIH) research initiative to improve understanding of the microbial
flora involved in human health and disease. Launched in 2007, the first phase
(HMP1) focused on identifying and characterizing human microbial flora. The
second phase, known as the Integrative Human Microbiome Project (iHMP)
launched in 2014 with the aim of generating resources to characterize
the microbiome and elucidating the roles of microbes in health and disease states.

7. Phase One (2007-2014)
The HMP1 included research efforts from many institutions.The
HMP1 set the following goals:
• Develop a reference set of microbial genome sequences and to
perform preliminary characterization of the human microbiome
• Explore the relationship between disease and changes in the
human microbiome
• Develop new technologies and tools for computational analysis
• Establish a resource repository
• Study the ethical, legal, and social implications of human
microbiome research

8. Phase Two (2014-2016)
In 2014, the NIH launched the second phase of the project, known
as the Integrative Human Microbiome Project (iHMP). The goal of
the iHMP was to produce resources to create a complete
characterization of the human microbiome, with a focus on
understanding the presence of microbiota in health and disease
states. The project mission, as stated by the NIH, was as follows:
The iHMP will create integrated longitudinal datasets of biological
properties from both the microbiome and host from three different
cohort studies of microbiome-associated conditions using multiple
"omics" technologies.

9. Achievements-
• Development of new database systems allowing efficient organization, storage,
access, search and annotation of massive amounts of data. These include IMG,
the Integrated Microbial Genomes database. Genomes Online Database(GOLD),
for monitoring the status of genomic and metagenomic projects worldwide and
their associated metadata.
• Development of tools for comparative analysis that facilitate the recognition of
common patterns, major themes and trends in complex data sets.
• Development of new methods and systems for assembly of massive sequence
data sets. Novel algorithms have been developed for improving the quality and
utility of draft genome sequences.
• Assembly of a catalog of sequenced reference genomes of pure bacterial strains
from multiple body sites, against which metagenomic results can be compared.
• Establishment of the Data Analysis and Coordination Center (DACC), which serves
as the central repository for all HMP data.

10. Study –
The problem of elucidating the human microbiome is essentially identifying
the members of a microbial community which includes bacteria,
eukaryotes, and viruses. This is done primarily using DNA-based studies,
though RNA, protein and metabolite based studies are also performed.
Studies can be performed using different techniques –
I. Shotgun Sequencing
a) Collection of sample and DNA extraction
b) Preparation of library and sequencing
c) Metagenome assembly
d) Contig binning
II. Marker gene analysis
III. Phylogenetic analysis

12. Classification of Microbiome –
1) Bacteria
a) Firmicutes
b) Bacteroidetes
c) Proteobacteria
d) Verrumicrobia
e) Actinobacteria
f) Fusobacteria
g) Cyanobacteria
2) Archaea
a) Methanogen
3) Fungi
a) Yeast
b) Candida
c) Malassezia
4) Viruses
a) Bacteriophages

13. BACTERIA
Class Sub-class Type Present at Benefits Disease
Firmicutes bacillus and
clostridium
Gram +ve Gut flora energy
resorption
diabetes and
obesity
Bacteroidetes
(opportunistic
pathogen)
Chlorobi, Fibro
bacteres
Gram-ve symbiotic
species in GIT
metabolic
conversions of
complex sugar
and proteins
obesity and irrit
able bowel
syndrome.
type1 and type-
2 diabetes
Proteobacteria Escherichia, Sal
monella, Vibrio,
Helicobacter, Y
ersinia, Legione
llales
Gram-ve Gut ,placenta,
lower tract
Metabolism
and in placenta
Inflammation in
women lower
tract

14. Archaea
Class Sub-class Type Present at Benefits Disease
Methanogen Methanobrevi
bacter smithii
Hydrogen
metabolizer
Human gut Microbial
fermentation
and yield
energy
Obesity
CVS problem
Type-2 diab
Colon cancer
Methanosph
aera
stadtmanae
Hydrogen
metabolizer
Human gut Convert
methanol to
methane
-

15. Fungus
Class Sub-class Type Present at Benefits Disease
Yeast Ascomycota
and
Basidiomycot
a
Commensal
and single
celled
GIT Balance flaura
Gut activity
Opportunistic
infection
Candida C. Albicans
C.ascalaphida
rum
C. Amphixiae
Commensal Vagina
Skin
Genitals
GIT
GUT
Glucose and
maltose to gas
and acid
Fungal infection
Opportunistic
infection

16. Anatomical areas
Skin
• A study of twenty skin sites on each of ten healthy humans found 205
identified genera in nineteen bacterial phyla, with most sequences assigned
to four phyla :-
Actinobacteria (51.8%), Firmicutes (24.4%), Proteobacteria (16.5%),
and Bacteroidetes (6.3%).
• A large number of fungal genera are present on healthy human skin, with
some variability by region of the body; however, during pathological
conditions, certain genera tend to dominate in the affected region. For
example, Malassezia is dominant in atopic dermatitis and Acremonium is
dominant on dandruff-afflicted scalps.

17. Conjunctiva
• A small number of bacteria and fungi are normally present in
the conjunctiva. Classes of bacteria include Gram-positive cocci
(e.g., Staphylococcus and Streptococcus ) and Gram-negative rods and
cocci (e.g., Haemophilus and Neisseria ) are present.
• Fungal genera include Candida, Aspergillus, and Penicillium.
• The lachrymal glands continuously secrete, keeping the conjunctiva
moist, while intermittent blinking lubricates the conjunctiva and washes
away foreign material. Tears contain bactericides such as lysozyme, so
that microorganisms have difficulty in surviving the lysozyme and settling
on the epithelial surfaces.

18. GUT
• In humans the composition of gut flora is established during birth.
• Birth by Cesarean section or vaginal delivery also influences the gut's
microbial composition.
• Babies born through the vaginal canal have non-pathogenic, beneficial gut
microbiota similar to those found in the mother. However, the gut
microbiota of babies delivered by C-section harbors more pathogenic
bacteria such as Escherichia coli and Staphylococcus and it takes longer to
develop non-pathogenic, beneficial gut microbiota

19. Urethra and bladder
The genitourinary system appears to have a microbiota which
is an unexpected finding in light of the long-standing use of
standard clinical microbiological culture methods to
detect bacteria in urine when people show signs of a urinary
tract infection.
As of 2017, sequencing methods were used to identify these
microorganisms to determine if there are differences in
microbiota between people with urinary tract problems and
those who are healthy

20. Vagina
• Vaginal microbiota refers to those species and genera that colonize the vagina. These
organisms play an important role in protecting against infections and maintaining vaginal
health..
• The most abundant vaginal microorganisms found in premenopausal women are from
the genus Lactobacillus, which suppress pathogens by producing hydrogen peroxide and
lactic acid.
• Bacterial species composition and ratios vary depending on the stage of the menstrual
cycle.
• Ethnicity also influences vaginal flora. The occurrence of hydrogen peroxide-producing
lactobacilli is lower in African American women and vaginal pH is higher.
• Other influential factors such as sexual intercourse and antibiotics have been linked to
the loss of lactobacilli.[
• Changes in the normal, healthy vaginal microbiota is an indication of infections, such
as candidiasis or bacterial vaginosis. Candida albicans inhibits the growth
of Lactobacillus species, while Lactobacillus species which produce hydrogen peroxide
inhibit the growth and virulence of Candida albicans in both the vagina and the gut.

21. Role of microbiota in Human Health
1. Symbiotic relationship: Interaction between two different
organisms living in close physical association, typically to
the advantage of both).
2. Shaping and maintaining immunity –
 Innate immunity
 Adaptive immunity

23. Gut Microbiota in Health- innate
immunity
• Produce pathogen associated
Molecular patterns (PAMPs) and
metabolic by products and
regulate intestinal immune
responses
• PAMPs are recognized by pattern
recognition receptor (PRR)-
bearing cells of the innate
immune system and many
epithelial cells

24. Gut Microbiota
in Health:
Adaptive
immune system
• Microbiota stimulation
leads to B cell switch to
IgA, regulatory T cell
induction, T cell
differentiation to Th17

25. Protective function (barrier effect)
• Compete and adhere to the attachment sites in the
brush border of intestinal epithelial.
• Compete for available nutrients.
• Produce antimicrobial (bacteriocins).
All of this will prevent attachment and subsequent entry of
pathogenic bacteria into the epithelial cells

27. Role of microbiota in
Disease

28. Density ,
diversity,and activity
of gut bacteria
Age ,
genetics ,
stress ,
physiological
processes ,
anatomical
structure and
physiology of
digestive
tract
Diet ,
prebiotics
,probiotics ,
antibiotic
usage , illness ,
lifestyle , living
environment
Health
Diseases
External influence
Internal host
properties

30. Dysbiosis: Proposed mechanisms leading to disease
• Genetic and environmental factors induce impaired barrier
function
• Overgrowth of pathogenic bacteria; inhibition of protective
bacteria
• Translocation of bacteria and bacterial products
• Immune activation and proinflammatory cytokine production
• Chronic inflammation leads to tissue destruction and
complications
• Leaky gut hypothesis

33. 1) Gastric diseases
a) Gastric cancer
b) Gastritis
c) Ulcer
d) Ulcerative colitis
e) Crohns disease
2) Liver disease
a) Non-alcoholic liver disease
b) Non-alcoholic steatohepatitis
3) Neurodegenerative disease
a) Alzheimer due to oxidative stress
b) Parkinson
4) Metabolic disorder
a) Obesity
b) Diabetes

34. Dysbiosis and diseases
• Diseases of the GUT
– Malabsorption syndrome
– Malignancies: Colorectal cancer
– Inflammatory Bowl disease (IBD)
– Irritable Bowl syndrome
– Diarrheal diseases
– Clostridium Difficile Infection (CDI)
• Non-mucosal diseases
– Obesity and metabolic syndrome
– Malignancies: liver cancer, breast cancer
– Complications of liver cirrhosis
– Allergic conditions
– Autoimmune disorders (T1DM, arthritis etc)
– Abnormalities of the gut-brain axis- Autism and
other neurological disorders
– Obesity and other metabolic disorders
– Chronic fatigue syndrome

35. Malabsorption syndrome
• In health: The bacterial growth is restricted in the upper small bowel under the
influence of acid and motility.
• Factors predisposing to bacterial overgrowth:
Surgical, anatomical, motor (scleroderma & DM), hypochlohydra (atrophic gastritis, post
gastrectomy)
• Consequences of bacterial overgrowth:
– Fat malabsorption due to:
• Bacteria deconjugation of bile acids which allows free bile acids to be
reabsorped decrease luminal bile acid concentration ---limit micelle
formation.
• Patchy mucosal damage by bacteria or toxic effects of FFA
– CHO and protein malabsorption due to mucosal damage or
bacterial metabolism of these nutrients.
– B12 malabsorption: B12 is utilized by the bacteria, in contrast
bacteria produces folic acid.

36. GIT malignancies: Colorectal cancer
Colonic bacteria may initiate cancer through:
1- Production of carcinogens from diets rich in meat and fat (nitroso
compounds).
2- Elevation in damage to DNA of colonic cells by dietary carcinogens
(heterocyclic aromatic amines found in cooked meat).
3- Abnormalities in repair can lead to neoplastic transformations
4-Microbial metabolism can produce by-products toxic to epithelium;
5- Disproportionate pro-inflammatory signalling at the GIT mucosa, leads to
increased sloughing and repair of epithelium, which can ultimately lead to
neoplasia and malignancy.
6-Certain microbial species can have direct or indirect (through host cell
activation) cytotoxic effects on cells

40. From Next time Don’t feel Lonely….cause you have some friends inside
you to take care of yourself……

41. REFERENCE
1. Human Microbiome and Its Association With Health and Diseases, ASMAA A.
ALTHANI,1,2 HANY E. MAREI, DOI: 10.1002/jcp.25284
2. The human microbiome in health and disease : hype or hope , Gwen Falony,
Doris Vandeputte , International Journal of Clinical and Laboratory Medicine
3. Sherwood, Linda; Willey, Joanne; Woolverton, Christopher (2013). Prescott's
Microbiology (9th ed.). New York: McGraw Hill. pp. 713–721.
4. "NIH Human Microbiome Project defines normal bacterial makeup of the body".
NIH News. 13 June 2012.
5. H Human Microbiome Working Group (2009). "The NIH Human Microbiome
Project". Genome Res. 19 (12): 2317–2323. doi:10.1101/gr.096651