8. Human Microbiome Flashcards
what is a microbiome?
all of the living Microorganisms in an environment
Microbiome vs microbiota
microbiome
- the entire habitat including the Microorganisms their genomes and the surrounding environmental conditions
microbiota
- the microorganisms present in a defined environment
what is one health?
studies looking at the link and interactions between humans, animals and the environment with disease
The importance of environmental biomes
without microorganisms we wouldn’t be here
bacteria and fungi are everywhere and are essential to life
what are the 3 host-microbe interactions?
Commensalism = one party benefits, the other is neutrally affected
Mutualism = both parties benefit
Parasitism = one party benefits, the other is harmed
what is a core microbiota?
a common set of microorganism that are present in a set of host eg all humans
- shared similarities within species but still individualised
- changes over time but many microorganisms present for many years
what can the core microbiota help us identify?
dysbiosis - the state of disease
can be used for diagnosis and monitoring can be used for prophylaxis
what do microorganisms acquired from birth develop into?
a distinct microbiome through environmental and genetic factors
what does a healthy microbiota look like?
- attached to the epithelial cells
- forms a protective layer on top of the cell
- produce antimicrobial peptides as prophylaxis and to keep the microbiota in check
what happens with depleted microbiota?
- less protection
- bacteria can get through the epithelial barrier
- cause disease
what can disrupt the normal microbiota?
- exposure to antibiotics
- changes in health or immunity
- hormonal changes
- local trauma
what microorganisms tend to be in the skin microbiome?
- Staphylococcus aureus
- Pseudomonas
- Streptococcus
what microorganisms tend to be in the Ear microbiome?
- Staphylococcus
what bacteria are mostly in the internal microbiota?
gram negatives and anaerobes
what microorganisms tend to be in the Oropharynx microbiome?
- Staphylococcus
- Viridans streptococci
- neisseria
what microorganisms tend to be in the stomach microbiome?
- helicobactor
what microorganisms tend to be in the small intestines microbiome?
- Lactobacillus
- bacteroides
- enterobacteriaceae
what microorganisms tend to be in the large intestines microbiome?
- Bacteroides
- fusobacterium
- E. coli
- Proteus
- klebsiella
- peptostreptococcus
- Enterococcus
what microorganisms tend to be in the vagina microbiome?
- Lactobacillus
- gardnerella vagunalis
- candida
Strep. Pneumonia
- infects the nasopharynx
- gram positive diplococci
- pneumolysin that breaks down cells
- causes meningitis and sepsis
- it has a range of effect depending where it is found
Pneumonia
- bacterial, viral or fungal
- viral pneumonia is a big problem
- most pneumonia causing microorganisms we can carry as commensals with no problem
what are biofilms?
an aggregate of microorganisms attached to a surface and/or each other, often embedded in a self produced matrix consisting of extracellular polymeric substances
why are bioflims a preferred mode of growth for microorganisms?
- the matrix is a protective physical barrier
- micro niches form with anaerobes on the inside of the biofilm and aerobes on the outside
- quorum sensing can occur easily
- sharing of plasmids and genetic information is easy and efficient
what are the 5 stages of biofilm formation?
- attachment - van Der Waals or ionic forces
- colonisation
- production of matrix - recruit proteins and microbes
- maturation
- dispersion - breakdown of the matrix and leaving the biofilm
Oral microbiota
- numerous different surfaces so everyone will have a different microbiota
- over 1000 microbial species in total
- mostly harmless
- some help break down food and aid digestion
- with out them pathogenic bacteria we inhale or ingest would be able to enter and infect the mouth
Parts of a healthy oral microbiome
- streptococcus
- actinomyces
- veilonella
disease-associated parts of the oral microbiome
- porphyromonas gingivalis
- treponema denticola
- tannerella forsythia
what is a red complex bacteria?
the presence of one these bacteria indicates the beginning of an infectious disease
what do primary colonisers bind to in the mouth to establish a community?
- sialic acid residues
- ß 1,4- linked galactose
what do secondary colonisers bind to?
similar receptors to the primary colonisers just on the primary bacteria not the host cells
example of secondary coloniser
Fusobacterium nucleatum
- considered a bridging microbe for the maturation of the biofilm and community
Oral disease: tooth decay/gum disease
- biofilm pockets that produce acids and break down enamel
- S. mutans
- C. albicans
- P. Gingivalis
Oral diseases: denture associated stomatitis
- C. albicans
- streptococci
- P. aeruginosa
Oral diseases: cancers
- C. albicans and other candida
- HPV 16 + 18
- Fusobacterium
- Clostridium
- Haemophilus
- enterobacteriaceae
Oral diseases: candidosis
- yeast/fungal
- caused by a disruption of community balance allowing one or more organism to grow uncontrolled
- almost always an underlying host predisposing factor
what can effect the amount of growth of disease organisms in the microbiome?
- the presence of other organisms
- presence of a specific organism
- metabolites
- chemicals
what can reduce pathogenicity of a C. albicans infection?
adding a specific bacteria like P. Gingivalis
what are the benefits of the oral microbiomes?
- produce amylase and protease to break down foods
- reduce colonisation of opportunistic pathogens
- contribute to oral health and overal health through metabolic by products
Respiratory tract microbiota
- host tolerance and clearance
- microbiome exclusion
- 1000s of fungal spores inhaled everyday but the microbiota prevents infection
Healthy components of the respiratory microbiome
- S. epidermidis
- viridans group streptococci
- Corynebacterium spp
- propionibacterium spp
- haemophilus spp
disease associated components of the respiratory microbiome
- S. pneumoniae
- S. pyogenes
- H. influenzae
- M. catarrhalis
link between the oral and respiratory microbiota
some opportunistic pathogens colonise the oral cavity as a means to get into the respiratory tract. things like intubation can the cause infection
need to monitor transmission between the 2 sites
GI tract mircobiome
- intestines = most colonised
- density gradient increasing from gut to large bowel
- gut = transient colonisation due to pH barrier
- 90-95% of the large bowel are anaerobes
Microorganism components of the stomach
- lactobacilli
Microorganism components of the small bowel - duodenum
- lactobacilli
- streptococci
Microorganism components of the small bowel - ileum
- enterbacteria
- bacteroides spp
Microorganism components of the large bowel
- bacteroides spp
- fusobacterium spp
- strep. faecalis
- E. coli
- Lactobacillus
- staph. aureus
Microorganism components of the rectum
- bacteroides spp
- bifidobacteria
- coliforms
host-microbe interactions - C.diff
- can be carried asymptomatically for long periods
- life threatening infections in the absence of other microbes
- treatment with broad spectrum antibiotics reduces microbiome diversity and colonisation
- C. diff thrives and takes over causing infection with toxins causing tissue damage
- spore forming so very resistant to treatment
- treat with antibiotics or faecal transplants
faecal transplants
spray the inside of the colon with extra bacteria
this can help reduce symptoms but doesn’t get rid of the spores
microbiome monitoring
- commercial companies offering at home analysis
- core microbiome profiling and looking for specific pathogens and normal ranges
- still in its infancy and screening for specifics
Microbiome and influence on drug efficacy
Positive:
form of a drug that is converted to its active form by Microorganisms in the gut
Negative:
Eggerthella lenta (in 40% of the population) can break down and inactivate digoxin that is used for heart failure
- increase the dose
- treat with antibiotics as well to reduce the bacteria?
Microbiome and drugs: multi-layer antimicrobial administration
- several layers of liposome coating with different antimicrobials in different layers
- targeted disruption of the membrane releases the next layer
- put certain drugs in the hydrophobic and hydrophilic areas
- good at tackling resistance and biofilms
the microbiome and the brain
the gut’s Microorganisms are known to impact neurological conditions such as:
1. Alzheimer’s
2. Parkinsons - E. coli curl protein causing protein misfolding
3. motor neurone disease - akkermansia muciniphila make vit B, aiding symptoms
4. Autism- possible infection during pregnancy
5. Anxiety
what are keystone microorganisms?
the microorganisms that even at low abundances can remodel a healthy benign community/microbiome into a disease causing microbiome through dysbiosis
OR those that are missing from a community can result in dysbiosis
generally reserved for pathogenic microorganisms
Example of a keystone pathogen
P. gingervalis
remodelling effects on the microbiome and the host
indirectly using the host immune system
OR
directly
how do we determine the microbiome?
- community profiling - taxonomical
- functional profiling - the role of microorganisms
- Ecological profiling - abundance, interactions, patterns
- Stability and variability
- NGS of 16S rRNA for bacteria and 18S rRNA for fungi (these have bias)
Next Gen Sequencing problems
if you don’t have the sequence you cannot determine if the sequence is present and 70% of the microbiota cannot be cultured to be sequenced
what are the unknowns about the microbiota?
- there is so much we don’t know about species/genera/phyla are present as not all can be cultured
- most may rely on other microbes to grow or have specific environmental conditions/supplementation
Probiotics vs prebiotics
Probiotics = microbes for healthy guts?
- not much scientific benefit
Prebiotics = foods for healthy guts?
- yes very good for you
