The Human Microbiome
The Biology of Microorganisms
• Microorganisms found across all three
domains of life
– Bacteria
– Archaea
– Eukarya
The Biology of MicroorganismsEukarya
• Although we typically think of
members of the domain Eukarya as
being large, multi-celled organisms,
there are in fact many eukaryotic
microbes
• Eukaryotic cells have membrane
bound structures called organelles
– Ex. nucleus, mitochondria,
chloroplasts
• Mitochondria and chloroplasts may
have originally been symbiotic
bacteria
• Microorganisms: protists, algae, fungi
The Biology of Microorganisms –
Bacteria
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Bacteria + archaea = prokaryotes
Most prokaryotes lack membrane bound organelles
Most prokaryotes and a have circular chromosome (and occasionally small circular plasmids)
Prokaryotes use cytoplasmic membrane to generate energy
Bacteria have diverse metabolism:
– Respire on oxygen, nitrate, sulfate, iron and many other compounds
– Can obtain energy from organic carbon, nitrite, ammonia, hydrogen, methane, sulfur, etc.
– Some are photosynthetic
The Biology of MicroorganismsArchaea
• Many are extremophiles
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pH
Temperature
Salinity
Pressure
• Some live under nonextreme conditions
• Structurally different from
bacteria:
– Cell membrane lipid
content
– Cell wall structure
– Flagella structure
Archaea are found in extreme places
such as: (a) swamps and sewage plants
(b) salt lakes (c) deep sea hydrothermal
vents (d) hot springs
The Biology of Microorganisms Viruses
• Not living organisms but
often still labeled as
“microorganisms”
• Have their own genome
• Unable to synthesize their
own proteins, replicate
themselves independently
and have no metabolic
capabilities
• Require the machinery of
the cell that they are
infecting to replicate
themselves.
The Human Microbiome
• For the past 500 million years animals have
hosted microbes in and on their bodies
– Microbes are often harmless and even cooperative
• Microbes help us in defending against pathogens
and help boost our metabolism. In return we
provide them with nutrients and a home
• Human microbiome – collection of microbes
within and on the human body
• Human microbiome varies across different body
sites and from person to person
Questions
1. Describe the differences in metabolism and
structure between bacteria, archaea, and
eukaryotes
2. Why are viruses not considered to be living
organisms?
3. Why do you think that the human
microbiome varies across different body
sites?
The Human Microbiome ProjectHistory
• Human Genome Project
(HGP) complete in 2006
– Led to advances in DNA
sequencing technologies
and bioinformatic methods
• Human Microbiome
Project (HMP) grew from
the HGP and began in
2007
• Main funding from the
National Institutes of
Health
The Human Microbiome Project Goals
1. Develop a set of reference microbial genome sequences
from the human microbiome and begin the preliminary
characterzation of the healthy human microbiome
2. Explore the relationship between disease and changes in
the human microbiome
3. Develop new tools and technology to analyze all the DNA
sequences
4. Create a place to store and share data with others
5. Create a place to store physical samples of DNA and
microorganisms that can be accessed by other researchers
6. Consider the ethical, legal, and social implications of the
research
The Human Microbiome Project –
Methods
• Challenges with sequencing the human
microbiome
– Thousands of different species of microorganisms
– Many of these bacteria are unable to be grown in
a laboratory
The Human Microbiome Project –
Methods
• 16S rRNA gene sequencing
– The 16S rRNA is a component of the 30S subunit
of prokaryotic ribosomes
– Gene encoding the 16S rRNA is often used in
phylogenetic studies in order to identify bacteria
present in a community and to map their
relationship to each other
The Human Microbiome Project –
Methods
16S rRNA sequencing
The Human Microbiome Project –
Methods
• 16S rRNA gene sequencing provides a good
estimate of who is there; however, this data does
not tell scientists about what the microbes could
be doing inside our bodies
• In order to get a better idea of how these
microbes live their lives inside our bodies,
scientists had to turn to metagenomic
sequencing.
• Metagenomics- the study of the total DNA
extracted from an environmental sample
The Human Microbiome Project –
Methods
Metagenomics
Map of the Human Microbiome
• Sites of the body with their own unique
microbiomes
– Skin
– Mouth
– Gastrointestinal tract
– Urogenital tract
Questions
1. What are the two methods that scientists use
to explore the human microbiome? What
information do these methods give us?
2.If you were a scientist working on the Human
Microbiome Project, what questions would you
try to address about the human microbiome?
What Your Microbes do for You
• Fighting off pathogens - Lactobacillus reuteri RC-14
produces one or more molecules that is capable of
inhibiting toxin synthesis by Staphylococcus aureus.
• Iron absorption - studies on mice that that lack gut
microbes suggest that there is a link between the gut
microbiota and the development of iron deficiency.
• Vitamin production – Gut microbes produce vitamin B12,
vitamin B6, vitamin B5, vitamin B3, biotin, tetrahydrofolate,
and vitamin K.
• Antooxidant production - Indole-3-propionic acid is a
powerful antioxidant found in the human body. A group of
GI tract bacteria have been implicated in the
transformation of indole to indole-3-propionic acid.
Questions
1. Why do you think that people take
probiotics? Do you think that they are
beneficial?
2. What might happen to a person who has
taken antibiotics?
Your Microbiome and Your Health
• Studies focus on observing how the microbial
communities of healthy and diseased individuals
differ and how the microbiome fluctuates over
the course of a disease so that a "disease
microbiome" can be established for different
complex conditions
• For many complex diseases it is believed that a
community of microorganisms, rather than one
pathogen, may lead to the development of
disease
Your Microbiome and Your Health
• Diseases associated with
an unhealthy microbiome
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Psoriasis
Skin ulcers
Inflammatory bowel disease
Obesity
Anxiety and depression
Colorectal cancer
Your Microbiome and Your Health
• Microbes may effect how your body
metabolizes druges
• Example: paracetamol and health supplement
metabolism
Questions
1. How do scientists figure out if disease
development is triggered by the
microbiome?
2. What are some ways that doctors could treat
diseases that are known to be associated
with an unhealthy human microbiome?
Personalized Medicine
Personalized medicine - a branch of healthcare
that utilizes a patient's unique clinical, genomic,
historical, and environmental information to
inform both the treatment of disease in that
individual but also to maintain a state of
wellness. The goal of personalized medicine is to
optimize healthcare for each individual rather
than the average person.
Personalized medicine
Personalized medicine
• The bacterial communities within you play a
major role in your body's day-to-day
functioning (or malfunctioning, in some
cases).
• The information known about the interactions
between the microbiome and disease
development and drug metabolism can help
doctors personalize healthcare to not to an
individual but also their microbes.
Questions
1. How does personalized medicine differ from
medical practice currently?
2. How can a person’s microbiome information
be used to personalize their healthcare?