Microbiota Flashcards
Intestinal bacteria are responsible for development of immune system; germfree animals will almost entirely lack ….
Intestinal bacteria responsible for development of immune system; germfree animals have almost no secondary lymphoid tissues including mucosal tissues.
Some but not all commensal bacteria can promote development of lymphoid tissues
couple major things that we know the commensals do for us: they develop the secondary immune system. if you have germ free mouse- almost no secondary lymphoid tissues. need bacteria to generate secondary lymphoid tissues (don’t know how yet but know you need it)
mucosal immunity- gut commensals are important for this. IgA coats lots of bacteria in gut, calms them and keeps them from getting in epithelial barrier
-protection from pathogens- keeps pathogens out
Describe how the treatment with antibiotics can affect a patient’s susceptibility to C. difficile.
Clostridium difficile disease. Treatment with antibiotics kill most
commensals, allowing toxin-producing C. difficile to become dominant
Colon is colonized by large numbers of commensal bacteria
Antibiotics kill many of these commensal bacteria
C. diff gains foothold and prod. toxins that cause mucosal injury
Neutrophils and RBC leak into gut between injured epithelial cells
patient w C diff- secrete spores, get all over bed walls instruments everywhere. next patient comes in and here are spores and they eat them and go through stomach and GI tract, now no one home to prevent them from colonizing. make toxins that destroy the epithelial layer and enormous inflammatory disease. if you don’t have antibiotics- then have normal micro biome and don’t get disease. many of us exposed to c.diff. but we don’t get it if we’ve haven’t been exposed to antibiotics
Germfree animals have:
a. secondary lymphoid tissues
b. C. difficile
c. mucosal tissues
d. proliferating B cell follicles
e. responses to B. subtilis more than B. fragilis
E
Slide 10
germ free animal w B. frag. introduced.
other organism B subtilis did stimulate B cells to proliferate and have nice follicles
so not every bacteria will do it.
Discuss how a dose of commensal Bacillus subtilis will affect a mouse model with enteric pathogen Citrobacter rodentium (infect w enteropathogenic E.coli/traveler’s diarrhea)
In mouse model using enteric pathogen Citrobacter rodentium, mice are protected from enteric disease by a single oral dose of the
commensal Bacillus subtilis
if give mouse some of this magic B. subtilis, then infect it with e coli then you have perfectly normal colon.
What regulates Th/Treg
cells?
Describe role of SFB.
Some bacteria promote
TH cells; others
promote Treg cells
Commensal microbiota balances pro- and
anti-inflammatory immune mechanisms
balance w right about to Thelper and Treg-this is immune homeostasis =dont get sick if too much T helper/inflammatory..can end up w disease
SFB can induce Th17 inflammatory cells which are needed to protect against pathogens. (need certain amount of Th17) other bacteria will help induce Treg.
Describe how dysbiosis can alter the balance of Th17/Treg.
How do you get dysbiosis?
Dysbiosis can favor pro-inflammatory
(TH17 and TH1) over
anti-inflammatory (Treg) state
antibiotics is a key reason, diet, toxins will alter microbiome, can have intestinal barrier defects
Th17 cells are needed for protection from pathogenic bacteria, but
overproduction of IL-17 can lead to intestinal inflammation; Th17 cells are
regulated by Treg cells; a “healthy” balance of Th17 and Treg cells is generated by a “healthy” intestinal microbiota. Dysbiosis can favor proinflammatory
status.
Would it be advised to treat IBD with B. subtilis or B. fragilis?
IBD can be treated by Bacteroides fragilis which induces an anti-inflammatory response
Will a T-bet/RAG/KO knockout mouse develop IBD?
T-bet-/- RAG-/- KO mice have altered gut microbiota (dysbiosis) and develop IBD
mouse w no RAG or T-bet… no T and no B cell, no adaptive immunity… these mice have dysbiosis (we know part of immune system you make IgA which helps protect from organisms in gut, without it you have altered gut microbiota and those mice develop IBD) diarrhea and inflamed colon…
take mouse w IBD and do fecal transplant into normal mouse… now that mouse gets IBD. so this shows IBD can be caused by intestinal microbiota. got wrong microbiota- if you have that, that can be transferred… shows micro biome can induce IBD.
IBD likely due to changes in development or
composition of intestinal microbiota (dysbiosis)
Dysbiosis can favor pro-inflammatory
(TH17 and TH1) over
anti-inflammatory (Treg) state
Explain why early life exposure to some microbes can alter
susceptibility to disease, particularly allergy.
(Which cytokines/Ig are increased/decreased?
Bacteria and viruses elicit Th1 responses (IL-2 and IFNg); Th1 responses downregulate Th2
responses (IgE- allergy); insufficient Th1 response due to decreased bacterial and viral infections would increase Th2 response (IgE).
How might depleted microbiota from antibiotics lead to allergy?
normal gut with lots of bacteria - interact w cells, end up w B cells that make IgM and IgG, when treated w antibiotics, not many microbes, when bacteria interact w B cells its a diff response, often you get IgE response (allergic)
Explain how Intestinal bacteria can protect from experimental autoimmune encephalomyelitis
(EAE). Is B. fragilis or B. subtilis more helpful in this scenario?
B. fragilis induces anti-inflammatory Treg cells which provide EAE protection
B. frag. induced DC, which induce Foxp3 reg T cells. T-reg can now protect mouse from EAE
What does fecal transplant from obese TLR5 KO mouse to antibiotic-treated wildtype result in?
How does high fat diet affects innate lymphoid cells? What do they secrete? What results?
Fecal transplant from obese TLR5 KO mouse to antibiotic-treated wildtype resulted in obese mice, showing that the microbiota can cause obesity.
High fat diet induces changes in the microbiota that can promote obesity: High fat diet affects innate lymphoid cells to secrete IL-22 which induces expression of anti-microbial Page 8
peptides which will alter the microbiota.
