Lecture 19: Microbiota Flashcards
Approximately how many different kinds of bacteria live in the large intestine?
1000
How are commensal gut bacteria beneficial to us?
1) provide energy by metabolizing dietary polysaccharides
2) provide vitamins
3) required for development of immune system (secondary lymphoid tissue)
4) protect from pathogenic bacteria
True or false: if you don’t have commensals, you don’t develop secondary lymphoid tissue
TRUE
Why are antibiotics dangerous?
they kill the resident commensal bacteria (therefore making them one of the best ways to change the microbiota)
Why is C. diff so common in hospitals?
because patients are on antibiotics so their gut microbiota is compromised/wiped out. C. diff travels via spores and gains a foothold/produces toxins that cause mucosal injury
Once C. diff has an entry way to the gut epithelium, what happens?
causese mucosal injury and neuts and RBCs leak into the gut between injured epithelial cells
connective tissue degradation leads to colitis and pseudomembrane formation
What is the ONE gut species that has been identified as important?
Bacills subtilis
What are probiotics?
bacteria that promote the gut colony to help with digestion, etc
How was b. subtilis experimentally proven to be important?
given to a mouse and it protected it from traveler’s diarrhea (aka E. coli)
How do commensals protect from intestinal inflammation?
balance of pro and anti-inflammatory immune reactions
some bacteria promote Th cells while others promote Treg cells
Which gut bacteria increases levels of FoxP3? (aka Tregs)
B. fragilis
What is dysbiosis?
an abnormal microbiota (changed by antibiotics, diet or sleep) can favor pro-inflammatory (Th17 and Th1) over anti-inflammatory (Treg) state
What is Inflammatory Bowel Disease/Crohn’s/ulcerative colitis?
diseases that come out of dysbiosis - doesnt seem to be pathogen associated but commensal bacteria initiate it (T cell mediated inflammatory response due to stimulation by microbial antigens)
no good treatment
How was IBD determined to be a disease caused by commensals and not autoimmune?
knock out T-bed and RAG (no T or B cells), do a fecal transplant from that mouse into a WT one and it develops IBD
Which gut bacteria is particularly important in commensal bug diseases like IBD?
B. fragilis (induces Tregs)
In addition to IBD, what other disturbances can gut microbes cause?
allergies, autoimmunity, metabolic syndrome
Why has a decline in infectious diseases paralleled a rise in immune disorders?
hygiene hypothesis
True or false: incidence of allergy is increased in children given antibiotics in the first year of life
TRUE
How did science figure out that intestinal microbes can protect from allergy?
had a normal mouse —> gave it antibiotics then exposed it to dust mite allergen (got allergies)
Why is a decrease in early exposure to bacteria and infection a risk factor for developing allergy?
bacteria and viruses elicit Th1 responses (via IL2 and IFNy)
Th1 responses downregulate Th2 responses (which produce IgE)
therefore, insufficient Th1 response due to decreased bacteria/viral infection would INCREASE Th2 response
In simpler terms, what is the immunological basis for the hygiene hypothesis?
Th2»Th1 when not exposed to bacteria and viruses
How do commensals play a role in allergy?
they regulate Th1 and Th2 responses
How can microbiota protect from autoimmune diseases like MS?
exploit B. fragilis to induce Tregs (generates tolerogenic DCs which can tone down the immune system and subdue autoreactivity)
How can intestinal microbiota cause metabolic syndrome?
transfer of gut microbiota from TLR5-/- mouse to antibiotic (gut compromised) treated WT, get obese WT mouse
