Human Microbiome Flashcards
(13 cards)
Define microbiota
the microorganisms living on and in the body
Define microbiome
the collective genomes harvoured by the microbiota
Define core microbiome
a set of shared genes found in a given habitat in all humans
Define an ecological landscape
A mosaic of interacting ecosystems or habitats (at any scale) in which areas are spatially heterogeneous in at least one key factor
What is an example of an ecological landscape?
the stomach microbiome, typically populated by Prevotella, streptococcus, veillonella, and helicobacter - secretion of stomach acid, digestion of macromolecules
What are three biologically relevant numbers?
100 trillion symbiotic microbes in and on every person
95% located in the GI tract
1.3x more microbes than human cells
What are nine likely functions for the microbiome in human physiology?
Digestion of otherwise inaccessible nutrients
Vitamin synthesis
Protection from pathogens
Regulation of innate and adaptive immunity
Metabolic rate
Metabolism of xenobiotics
Odour
Behaviour
Cardiac size
What is an example of our gut microbiota protecting us from pathogens?
Bacteroidia and Clostridia species turn non-digestible polysccharides into SCFAs
Acetate, propionate, butyrate
These stimulate regulatory T-cells, which suppress inflammation by producing IL-10 and limiting expansion of CD4+ effector T cells
How does antibiotic use lead to loss of competitive exclusion?
Normal intestinal microbiota prevent C diff from colonizing and surviving in the lower GI tract
Compete for localized colonization sites, essential nutrients and metabolites, conversion of stuff to compounds inhibitory to C diff
Commensal bacteria are eliminated, spores germinate in response to bile acids
What is the pathogenesis of C diff?
six steps
C diff spores and vegetative cells are ingested
Most vegetative cells are killed in stomach acids
Spores survive acidic environment
C diff spores germinate in the small bowel upon exposure to bile acids
Flagellae facilitate c diff movement, a polysaccharide capsule discourages phagocytosis
C diff multiples in the colon
Gut mucosa facilitates adherence to the clonic epithelium
What is the mechanism of TcdA and TcdB?
five steps
Combined repetitive oligopeptide repeat (CROP) domain binds to cell surface receptors
Toxin is endocytosed and the crop domain facilitates transport of cysteine protease domain (CPD) and glucosyl transferase domain (GTD)
Binding of host IP6 activates the CPD
Activated GTD glycosylates RHO and RAC GTPases, which inactivates them
Disfunction of tight junctions and loss of tissue integrity
What is the mechanism of CDT?
Binary toxin
Binds to the LSR receptor and is internalized
CdtB creates a poire in the endosome that facilitates the release of CdtA
CdtA inhibits actin polymerization via ribosylation of actin
Causes fibronectin protrusion, increasing attachment sites for C diff
How does an FMT treat CDI?
Involves instilling normal flora from a healthy donor into the colon of a patient suffering from rCDI
Restores competitive exclusion and has been shown to be highly effective at treating rCDI
