L5: Gut Microbiome and Cancer and Cancer Immunotherapy (D. Philpott) Flashcards
microbiome
theatre of activity + community of microorganisms
microbiota
assemblage of microorganisms present
largest diversity and number of bacetria
colon
2 main phyla: Firmicutes and Bacteroidetes
development of microbiota
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
dysbiosis
altered microbiota - associated with disease
compositional and functional changes
IBS, GI cancers, T1Diabetes, infectious disease, T2Diabetes, obesity, atherosclerosis
factors that might impact microbiota composition
diet, lifestyle, antibiotics, hygiene
how do we assess composition of microbiota
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
metagenomic shotgun sequencing
more expensive but more info about functionality of microbiome
take fecal matter - sequence everything
using germ-free mice to study contribution of microbiota to host health and disease
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
role of microbiota in allogeneic hematopoietic stem cell transplantation
simpson index high diversity correlated with survival for patients with blood cancers
simpson index, alpha diversity
a measure of how well represented each taxon is relative to others
high diversity = healthy microbiota
role of microbiota in allogeneic hematopoietic stem cell transplantation: use of antibiotics
decreased diversity = greater mortality
ICI (Immune checkpoint inhibitors) efficacy correlates with…
mutation burden
high levels of PD-L1 expression
profile of gut microbiota
cancer patients treared with ICI got antibiotics
led to decreased OS
role of the microbiota in anti-PDL1 cancer therapy
JAX microbiome has a specific abundance –> associated with greater CD8 T cell infiltration of tumors