L5: Gut Microbiome and Cancer and Cancer Immunotherapy (D. Philpott) Flashcards

1
Q

microbiome

A

theatre of activity + community of microorganisms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

microbiota

A

assemblage of microorganisms present

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

largest diversity and number of bacetria

A

colon
2 main phyla: Firmicutes and Bacteroidetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

development of microbiota

A

fetus sterile until birth
vaginal delivery vs cesarean delivery dictate which type of organisms first colonize the infant
infant: milk consumption and solid food introduction
toddler: full adult diet –> adult-like microbiota

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

dysbiosis

A

altered microbiota - associated with disease
compositional and functional changes
IBS, GI cancers, T1Diabetes, infectious disease, T2Diabetes, obesity, atherosclerosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

factors that might impact microbiota composition

A

diet, lifestyle, antibiotics, hygiene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

how do we assess composition of microbiota

A

through 16s rRNA amplicon sequencing
16s rRNA is the RNA portion of the ribosome - highly conserved in all bacteria (specific to bacteria) V4 region, PCR
this can help us understand which gene is associated with which bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

metagenomic shotgun sequencing

A

more expensive but more info about functionality of microbiome
take fecal matter - sequence everything

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

using germ-free mice to study contribution of microbiota to host health and disease

A

born and raised in sterile conditions, HEPA filter
have a tendency to consume more calories, weigh less (bacteria important for breaking down food), live longer
very little IgA, no development of GALT, very few T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

role of microbiota in allogeneic hematopoietic stem cell transplantation

A

simpson index high diversity correlated with survival for patients with blood cancers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

simpson index, alpha diversity

A

a measure of how well represented each taxon is relative to others
high diversity = healthy microbiota

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

role of microbiota in allogeneic hematopoietic stem cell transplantation: use of antibiotics

A

decreased diversity = greater mortality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

ICI (Immune checkpoint inhibitors) efficacy correlates with…

A

mutation burden
high levels of PD-L1 expression
profile of gut microbiota

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

cancer patients treared with ICI got antibiotics

A

led to decreased OS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

role of the microbiota in anti-PDL1 cancer therapy

A

JAX microbiome has a specific abundance –> associated with greater CD8 T cell infiltration of tumors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

role of microbiota in anti-CTLA4 cancer therapy

A

Didn’t work in germ-free mice= microbes are crucial for efficacy of therapy
Antibiotics similarly reduced efficacy of anti-CTLA4

17
Q

role of microbiota in humans treated with ICIs

A

Transfer of responder microbiota compared to nonresponder microbiota into germ-free mice correlates with response to anti-PD1
Greater CD4/ fewer Tregs in tumors
Prove causation of these microbes of promoting efficacy of cancer therapy

18
Q

how do microbes impact ICI outcomes - caveats with microbial studies

A

Increase levels of CD8 + T cells
Alterations of tumor microenvironment (bacterial translocation and infiltration of tumor)
Cross reactive antigens (anticancer or antimicrobial T cell response boosts ICIs)

19
Q

ways to modulate gut microbiota to improve ICI outcomes

A

Fecal microbial transplants
Probiotics/ bacteria consortia
Pre-biotics -metabolites for bacteria to break down complex carbohydrates
Postbiotics

20
Q

knowing that microbiome affects tumor progression, describe the strategy to mitigate any microbial effects on your animal experiments. How would you ensure your strategies worked

A
  • Co-house animals
  • Give antibiotic treatment then FMT for desired microbiome
  • Do 16S rRNA sequencing/shotgun sequencing to ensure microbiomes are the
    same from each mouse strains