Lecture 8 - Manipulating the Microbiota Flashcards
3 characteristics of disease-associated microbiota
- reduced diversity
- reduced metabolism
- reduced O2 –> increased anaerobes
3 methods to convert disease-associated to homeostastic microbiome
- FMT
- probiotics
- prebiotics
2 characteristics of health-associated microbiome
- increased CD8+ T cell stimulation
- altered metabolic profile
3 ways that homeostatic microbiome is converted to health-associated microbiome
- drugs
- probiotics
- prebiotics
is it easier to convert from disease-associated to homeostasis OR homeostasis to health-associated? why?
easier to convert from disease-associated to homeostasis
homeostatic microbiome is already established so harder to leave this state
when can C. diff infect microbiome?
when there’s loss of diversity –> C. diff can develop
how does C. diff damage GIT?
releases toxins that damage epithelial cells
why do most antibiotics not work for C. diff?
naturally resistant
usual treatment for C. diff and consequence
antibiotics that can kill C. diff –> but this will continue depleting microbiota making them even more susceptible to infection after treatment
what is a better treatment than antibiotics for C. diff?
FMT
is FMT only helpful for C. diff infection?
no, also helps other bacteria!
other bacterial infection that can be treated with FMT?
vancomycin-resistant enterococcus
describe FMT in allogeneic hematopoietic stem cell transplant
- microbiome is compromised in HPSC transplant and becomes susceptible to other infections
- did autologous FMT and microbiome returned to normal
what is autologous FMT?
stool sample before antibiotics, then give back stool after treatment
when is autologous FMT helpful?
when you know a treatment will severely mess up microbiota
benefit of FMT
straightfoward
4 downsides of FMT
- standardization issues
- safety issues
- colonization issues
- administration
why is standardization an issue with FMT?
cannot standardize! samples always different
what are the safety concerns with FMT?
- don’t know what you’re transplanting (don’t know all microorganisms)
- unclear what is a “healthy” donor
what are the colonization issues with FMT?
microbiota has been wiped out so the new microorganisms will colonize but might not actually colonize! the transplanted bacteria may be taking up space and preventing new bacteria from developing –> less diversity
issue with commercial probiotics
bacteria survive GIT and then get excreted –> rarely colonize host
diversity in microbiome after antibiotic treatment:
FMT vs nothing vs probiotics
FMT: microbiota diversity returned to what it was before antibiotics
nothing: takes longer to return but eventually returned to what it was before antibiotics
probiotics: diversity never returns to what it was before antibiotics
why might probiotics help C. diff? (3)
- bacteria can modify bile acids to make SECONDARY bile acids that inhibit C. diff germination
- bacteria will anti-bacterial components
- bacteria will compete for nutrients
what type of drugs are most helpful for recurrent C. diff infection?
live bacteria therapeutics
