Human Microbiome Flashcards
1) Understand the distribution and abundance of microbes on/in the human body (and which microbes are dominant in each area of the body). 2) Understand the human body as a series of microbial ecosystems 3) Review/know how physiological traits (e.g. fermentation) of select members of our microbiome affect Human health
Microbiome/Microbiota (definition)
all the microbes associated with an organism (such as the human body) OR with a habitat (such as a type of soil).
Holobiont
An organism and all their associated microorganisms
Example of a “simple” microbiome
The microbiome of colonies of microbes (biological soil crusts) growing near a receding glacier in the high Arctic.
Human microbiome: our microbiome consists of…
the bacteria, archaea, viruses, and microeukaryotes that live in and on our bodies
Our microbiome contains ____ as many bacterial cells as human cells
10x
* Bacterial cells: total human cells = 1.3 (about equal)
* Bacterial cells: nucleated Human cells (RBCs removed) = 10:1
* > 10 trillion microbial cells in/on a human
amount of human genes vs. microbial genes
100 or 1000x more microbial genes
* 20,000 human genes
* 20 million microbial genes
bottom line of having 100 or 1000x more microbial genes than human genes
our microbiome provides us with important traits
What things are microbe-free in healthy animals
blood, organs, and cerebrospinal fluid
Our microbiome is necessary for…
optimal function of our body system
What happens if some members of the microbiome overgrow or escape their usual location
they can cause disease
Coevolution with our microbiome
Over millions of years, we coevolved together with bacteria through exposure to what
commensals, soil bacteria, food fermenting bacteria, etc
Which systems in our body have adapted evolutionarily such that they are dependent on these microorganisms in order to function optimally
immune and digestive system
Hygiene hypothesis
Essentially its good not to be too clean
* exposure to commensals, soil bacteria and fermenting bacteria led to a “good” microbiome which = proper development of our immune system
* Sterile, indoor lives and over-cleanliness might be responsible for many conditions such as allergies, chronic inflammatiory disease, and various immunological disorders
How is the normal microbiota of our bodies also viewed as par of our innate immunity to pathogens
By colonizing the available niches of our bodies and releasing primary and secondary metabolites, they make it very difficult for foreign pathogens to colonize our skin and mucosal surfaces.
handwashing removes what % of transient bacteria and what % of resident bacteria
90% of transient bacteria
40% of resident bacteria
Presence of skin microbiota inhibits infection by what
Staphylococcus aureus and other pathogens
Is handwashing good?
Overall, yes, but too many showers or use of antibacterial soup on the whole body can remove helpful bacteria
An epidemiologist investigating an outbreak of bacterial skin infections caused by Pseudomonas aeruginosa discovers that all the affected people were healthy young adults who had attended the same pool party. Testing revealed low levels of P. aeruginosa cells (and other hardy bacteria) in the pool, but that the level of chlorine in the water was three times higher than the recommended concentration. What is the best explanation for the outbreak?
The chorine in the pool killed too many of the natural skin microbiota, thus opening up niches for P. aeruginosa to colonize.
overall point: anything that removes or kills natural skin microbiota makes us susceptible to infection
Why do we compare the human body to a planet
From the perspective of microbes the human body is like a planet with many different environments that are colonized by different microbes. Each region (habitat) of the human body has a unique microbiome
How do we use Prevotella as an example of there not being necessarily the same species of the same genus across different body zones
vagina = Prevotella amnii
gut = Prevotella copri
The mouth, teeth, and throat are dominated by
Teeth has two
Streptococcus
* teeth = Streptococcus and Corynebacterium
The skin is dominated by
Gram + bacteria
* Firmicutes (Staphylococcus)
* Actinobacteria (Propionibacterium, Corynebacterium)
These also dominate the nose since these location are very similar!!
The vagina is dominated by
Lactobacillus
Example of coevolution in the mouth - digestion of starch
In the mouth Streptococcus gordonii captures humans amylases with Amylase binding proteins (Abps) to digest starch extracellularly leading to the production of lactic acid
Main Phyla associated with the human body
- Bacteroidetes: Gram -, mainly break down polymers like cellulose (e.g. Prevotella, Bacteroides)
- Actinobacteria: Gram +, cutibacterium (Prorionibacterium), Corynebacterium, etc
- Firmicutes: both spore formers (Clostridiales), and non-spore formers (Staphylococcus, Streptococcus, Lactobacillus)
Why is the skin the most difficult place for microbes to live
- Dry
- Acidic (pH ~5.5)
- Salt
- Sebum (oily, waxy)
Would you expect to find more gram-positive or gram-negative bacteria on skin (and why)
Gram-positive: thicker cell wall, usually adapted to drier environments
What aspects of the skin are not uniform
- pH
- moisture availability
- temperature
- UV exposure
- O2/CO2
Number of bacterial cells just on skin surface (forhead, armpit, back, forearm)
Forehead: 2x10^5
Armpit: 2x10^6
Back: 3x10^2
Forearm: 1x10^2
Where is the greatest diversity on the human face
inbetween the eye - third eye?
still very big diversity everywhere on the face
Which actinobacterial name can be remebered by thinking of Cuniform writing
Coryneform bacteria (Corynebacterium)
- resemble the wedge shaped characters
Which actinobacterial name can be remebered by Latin cutis = skin, cutin = waxy substancer in the “skin” of plants, and the word cuticle
Cutibacterium
skin propionibacterium are now known as
Cutibacterium
human skin microbiome is Gram…, high…, and Phylum…
Gram +, high GC, Phylum Actinobacteria
What makes up about 80% of the bacteria in hair follicles
Cutibacterium acnes
What can Cutibacterium acnes ferment? Why is this important
can ferment lactic acid to propionate and can ferment glycerol
3 Glycerol -> propionate + acetate + lactate + 2 CO2
* This is important because sebum contains glycerol
Cutibacteriums ability to ferment glycerol to produce propionic acid and other fatty acids does what to pH and the skin
lowers the pH and helps protect the skin from pathogens
* “skin probiotic”
Cutibacterium acnes can also be a bad guy and cause
acne
Sebaceous glands
open into hair follicles and secrete oily/waxy sebum, which lubricates the hair and skin of mammals
In humans, sebaceous glands occur in the greatest number on the
face, scalp, and back
What causes acne
increase production of sebum due to hormonal factors = blockage of duct that can lead to infection by Cutibacterium acnes
Leads to inflammation causing the characteristic acne lesions
Cutibacterium acnes is a commensal bacterium living in hair follicles and can ferment glycerol in sebum to propionate, acetate, and lactate. This reduces the pH of the skin and inhibits the growth of …..
pathogens such as Staphylococcus aureus.
However, when there is excess sebum production, pores can become plugged and C. acnes can become an …..
pathogen by overgrowing and triggering an
inflammatory response.
opportunistic; opportunistic
Relationship between Cutibacterium from skin and Propionibacterium from cheese
While both strains of Propionibacterium, Propionibacterium from cheese are different strains than Cutibacterium from skin - share a fairly recent common ancestor, but have each evolved to the biome that they live in - definitely not within the same genus
also true of the lactic acid bacteria that we talked about earlier in the course, that is strains of Lactobacillus in cheeses and yogurt are not the same strains found in/on the human body
Herbivores in general depend more on……. in their guts compared to omnivores and carnivores
This is similar to
nitrogen fixation; similar to termites that depend on N-fixers to get their protein
How does a cow that eats only dry hay get enough protein?
large fermentation vessel (Rumen) w/ many N-fixing bacteria and archaea
* they convert unusable nitrogen gas into a usable form that helps plants make protein
* when fed into the stomach, acid kills them and releases the amino acids which the cow then absorbs
Location of fermentation chamber in cows and sheep (rumen) vs. humans and horses (cecum and large intestine)
Some animals (e.g. cows, sheep) have their major fermentation chamber (e.g. rumen) before the acidic stomach and some animals (e.g. humans, horses) have their fermentation chamber (cecum and large intestine) after the acidic stomach.
Sites of fermentaiton in animals is also the site of most
N-fixation
What is the equivalent (somewhat) of the Rumen in humans
tiny Cecum
Along the length of the GI tract what increases, what decreases
- microbial biomass increases
- O2 levels decrease
Characteristics of the small intestine
* major bacteria present
* what mainly happens here
* transit time
- Enterococcaceae
- Lactobacillales
- Absorbance of many nutrients
- Short transit time, antimicrobial compounds
Characteristics of the large intestine (Colon)
* major bacteria present
* what mainly happens here
* transit time
- Anaerobic decomposers like Bacteroides and Prevotella
- Break down complex carbs and proteins into products that can be absorbed by the body
- Long transit time
Function of anaerobic decomposers like Bacteroides and Prevotella in the colon
to hydrolyze large glycans (e.g. cellulose and starch) using extracellular enzymes
what makes up 60% of fecal mass
microbial cells
function of anaerobes fermenting sugars in the colon
ferment sugars to short chain fatty acids (e.g. acetate) that feed other microbes and are taken up by our cells
Function of facultative aerobes (e.g. E. coli) in the colon
scavenge all O2 keeping the lumen anaerobic
Function of some fermenters (e.g. some Bacteroidetes) releasing peptides in the colon
peptides act as signals (neurotransmitters) to the brain and nervous system
Main microbe components of the colon (large intestine) - Phylum, Gram, examples
2 main components
* Firmicutes (Gram +, lactobacillus, clostridium, christensenella)
* Bacteroidetes (Gram -, Bacteroides, Prevotella)
also many Proteobacteria (E.coli) and Actinobacteria (Bifidobacterium)
Biochemical/metabolic contributions of intestinal microbes
- vitamin synthesis
- amino acid synthesis
- organic acid production
- breakdown of large polymers using extracellular enzymes
- production of neurological agents
- nitrogen fixation
- gas production
- odor production
Bacteroides & depression
GABA-modulating bacteria of the human gut
* more GABA = less depressed
The most abundant virus in the human colon infects what species
bacteroides
so important in all aspects of the colon
Other than Bacteroides in the colon, where else did we talk about this species being dominant
Soil
* breakdown complex polysaccarides (starch, cellulose)
ON FINAL
Vicuna dung gardens
decomposes, turns into soil and allows things to grow in nutrient poor environments
* dominanted by Bacteroides - but shifted from the anaerobes of the colon to aerobic Bacteroides found in soil
* First thought to be from the Vicuna, but turned out to be aerobic soil Bacteroidetes
Archaea in the colon - mostly? do they work with in tandem with anything else?
Archaea make up 10-30% of microbes in the colon
mostly methanogens (Euryarchaeota)- many of them are living syntrophically with fermentative members of the Clostridiales
Methanogenesis equation
Syntrophic transfer of H2 by ethanol fermenter and methanogen
Ethanol fermenter produces H2 and Acetate, with is taken up by methanogen and used with CO2 to produce CH4
M. smithii (methanogen in colon) is syntrophically associated with what? what does this allow
fermentative Clostridiales (producing H2)
Removal of H2 by M. smithii allows more fermentation and the production of more acetate
Methanogens remove H2 = increased …. = increased …..
More methanogens = more
increased acetate = increased fat production
more flatulence (methane)
Colon microbiome affects what in conjunction with diet
obesity!
- Microbiome from an obese human twin cause mouse to be
- Microbiome from lean human twin caused mouse to be
- Obese mice living with lean mice acquired
- obese
- lean
- lean microbiome and lost weight
Effect of Christensenella minuta on body fat
reduced body fat - correlated with BMI
Christensenella minuta phylum and order
Phylum Firmicutes
Corder Clostridiales
* anti-inflammatory
Are Archaea in the colon aerobic?
No!
Characteristics of Bifidobacterium
Original probiotic
* Actinobacteria
* Named because of Y shape (Bifid)
* Ferment milk-based oligosaccharides (short chain polysaccharides)
* Important in early development of the gut microbiome and infant nutrition
Successiuon of the human microbiome during infancy (breast-fed infant)
- Bifidobacterium decrease as breast feeding stops ~12 months
- Bacteroides increases as diet changes to plant-based saccharides
Bifidobacterium -> Bacteroides
What is Bifidobacterium (Bifidus) added to
yogurt and other foods as a probiotic
Probiotics
- Live microorganisms which confers a health benefit when consumed
Two main genera of probiotics
- Lactobacillus and Bifidobacterium
Ways probioitcs work
- inactivation of bacterial toxins
- competition with pathogens
- up-regulation of immunity
- suppression of inflammation
- promotion of intensinal barrier function
Prebiotics and how they work
Non-digestible food ingredient
* stimulate growth/acitivty of specific bacteria (e.g. Bifidobacterium)
The human virome: what two things are also important members of the human microbiome
Bacteriophage and Archaeal viruses
what aspect of the human virome leads to recycling of nutrient in the gut and may kill some pathogens
lysis of cells
Lysogeny can lead to
good and bad traits
* enhanced triats
* Virulence such as toxins
Thru what mechanism can phage enter our bodies thru the epithelial cells of the colon
transcytosis
Why might transcytosis of phage particles occur
- priming of immune system
- circulating phage to kill bacteria
- digesting phage as food source
- Maybe no reason
Mechanism of Bacteriophage adhering to mucus
- phage adhere to mucus through Ig-like domains
- Adherent phage form anti-microbial layer
- Increased replicative success when adhered to mucus
