The Human Microbiome

The Biology of Microorganisms

• Microorganisms found across all three domains of life– Bacteria– Archaea– Eukarya

The Biology of Microorganisms- Eukarya

• 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

• 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 Microorganisms- Archaea

• Many are extremophiles – pH– Temperature– Salinity– Pressure

• Some live under non-extreme 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 Project- History

• 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– 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?