The concept of the human microbiome was first suggested by Joshua Lederberg, who coined the term ‘‘microbiome, to signify the ecological community of commensal, symbiotic, and pathogenic microorganisms that literally share our body space’’
3. The concept of the human microbiome was first suggested
by Joshua Lederberg, who coined the term ‘‘microbiome, to
signify the ecological community of commensal, symbiotic,
and pathogenic microorganisms that literally share our body
space’’
Human Microbiome Project (HMP) resources, including 600
microbial reference genomes, 70 million 16s sequences, 700
metagenomes, and 60 million predicted genes from healthy
adult microbiomes
The Human Microbiome Project
(HMP) is one of the largest
biological projects of all time
4. An international meeting was held in Paris in November 2005
to discuss such an effort
This meeting, hosted by the French National Institute for
Agricultural Research (INRA) and chaired by Dusko Ehrlich, led
to the recommendation that a Human Intestinal Metagenome
Initiative (HIMI) be undertaken to define more completely the
human intestinal microbiome in health and disease
Directly following the Paris meeting, the NIH held discussions
about the merits of initiating an NIH-sponsored HMP to study the
human microbiome broadly by examining at least four body sites
(the gastrointestinal tract, the mouth, the vagina, and the skin)
History
5. Where is the microbiome located, and
what is it doing?
The human is exposed to the outside world, there is a
microbial community. That means the entire surface of
the skin, and the lining of the nasal passages, lungs,
digestive and microbial cummunities. Some of these
communities are extremely dense and other more sparse.
What the microbiome is doing also varies from place to
place and many of its function have not yet been worked
out
6.
7. Bacterial distribution by body site
This figure shows the distribution by body site of bacteria that have
been sequenced under the HMP or are in the sequencing pipelines.
8.
9.
10. What is the relationship between the
microbiome, health and disease?
There have been many studies that show a correlation between
certain mixtures of microbes and certain disease states, but
evidence that any particular microbial community actually
cause a particular disease is still limited
The early history of microbiology was dominated by the quest
to identify the microbes responsible for disease, and find ways
to stop them
Identification and study of causative agent was the first step in
developing ways to prevent and cure infectious diseases
11. How Many different organism are normally in our
body?
Mouth : > 600 species
Skin : > 600 species
Intestine : (Cecum/colon) > 800 genera
Vegina : > 600 species
12. The participants were four large-scale
sequencing centers supported by NIH
1. The Baylor College of Medicine
2. The Broad Institute
3. The J. Craig Venter Institute
4. The Washington University School of
Medicine (Washington)
13. These will include 32 tribes as well - from Changpa in Ladkah to
Warli in Maharashtra and Mankidia in Odisha, and from Ao in
Nagaland to Koya in Telangana
After collecting the samples, scientists will sequence the genome
of these microorganisms
The HMP is a collaborative effort between 11 research institutes
and universities across the country, both public and private,
including the All India Institute of Medical Sciences in New Delhi,
the Insitute of Advanced Study in Science and Technology in
Guwahati and Symbiosis International University in Pune
The study is being led by Pune’s National Centre for Microbial
Resource (NCMR), which is part of the National Centre for Cell
Science
Human microbiome project: India
14. launched in 2008 to use culture independent methods to
characterized the microbial community living within us or
on us
10x more cell than we have (mostly in the GI tract)
100 x more genes than we have
Our microbes are mostly bacteria but include archaea,
eukaroyotes and viruses
15. 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
Program received $170 million in funding by the NIH
Common Fund from 2007 to 2016
16. HMP is not a single project, but rather a
summation of multiple projects that are now
being launched, concurrently, in multiple
areas of the world, including the USA (as
part of the next phase of NIH’s Roadmap
Initiative), the European Union, and Asia
HMP will address some of the most inspiring,
vexing and fundamental questions in 21st
century science
Importantly, it promises to break down the
artificial barriers between medical and
environmental microbiology
17. (1) To take advantage of new, high-throughput technologies to
characterize the human microbiome more fully by studying
samples from multiple body sites from each of at least 250
‘‘normal’’ volunteers
(4) The ultimate objective of the HMP is to demonstrate that
there are opportunities to improve human health through
monitoring or manipulation of the human microbiome
The goals of the HMP are:
(2) To determine whether there are associations between
changes in the microbiome and health/disease by studying
several different medical conditions
(3) To provide both a standardized data resource and new
technological approaches to enable such studies to be
undertaken broadly in the scientific community
18. 1. Develop a reference set of microbial genome sequences and
to perform preliminary characterization of the human
microbiome
2. Explore the relationship between disease and changes in
the human microbiome
3. Develop new technologies and tools for computational
analysis
4. Establish a resource repository
5. Study the ethical, legal, and social implications of human
microbiome research
Phase One (2007-2014)
In 2013, the HMP1 ended with over 14
terabytes of data from 300 individuals.
19. It creates datasets of biological properties from both the
microbiome and the host, focusing on three different topics
Onset of Type 2
Diabetes
Onset of
Inflammatory Bowel
Disease (IBD)
Pregnancy &
Preterm Birth
Much of our understanding of the human microbiome
comes from culture-based approaches using the 16S rRNA
technology
It is estimated that as much as 20% to 60% of the human-
associated microbiome, depending on body site, is
uncultivable
20. “These sugars are not broken down by the infant,” said Prof
John Cryan, a neuropharmacologist and microbiome expert
from University College Cork. Instead, microbes in the
baby’s gut do the job
Studies have suggested that these differences could be one of
the reasons why babies born by caesarean section have a
higher risk of conditions including asthma and type 1
diabetes
Some say we should be seen as a holobiont, a term that
reflects the intimate, co-dependent relationship humans have
with microbes
21. 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 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
22. Findings
• Microbes contribute more genes responsible for human
survival than humans' own genes. It is estimated that
bacterial protein-coding genes are 360 times more abundant
than human genes
• Microbial metabolic activities; for example, digestion of fats;
are not always provided by the same bacterial species. The
presence of the activities seems to matter more
• Components of the human microbiome change over time,
affected by a patient disease state and medication
• However, the microbiome eventually returns to a state of
equilibrium, even though the composition of bacterial types
has changed
23. Achievements
1. New predictive methods for identifying active transcription
factor binding sites
2. Identification, on the basis of bioinformatic evidence, of a
widely distributed, ribosomally produced electron carrier
precursor
3. Time-lapse "moving pictures" of the human microbiome
4. Identification of unique adaptations adopted by segmented
filamentous bacteria (SFB) in their role as gut commensals.
SFB are medically important because they stimulate T helper
17 cells, thought to play a key role in autoimmune disease
Achievements
24. 5. Identification of factors distinguishing the microbiota of
healthy and diseased gut
6. Identification of a hitherto unrecognized dominant role of
Verrucomicrobia in soil bacterial communities
7. Identification of factors determining the virulence
potential of Gardnerella vaginalis strains in vaginosis
8. Identification of a link between oral microbiota and
atherosclerosis
9. Demonstration that pathogenic species of Neisseria
involved in meningitis, sepsis, and sexually transmitted
disease exchange virulence factors with commensal species