Lecture 19: Microbiota

Question 1

Approximately how many different kinds of bacteria live in the large intestine?

Answer 1

1000

Question 2

How are commensal gut bacteria beneficial to us?

Answer 2

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

Question 3

True or false: if you don’t have commensals, you don’t develop secondary lymphoid tissue

Answer 3

TRUE

Question 4

Why are antibiotics dangerous?

Answer 4

they kill the resident commensal bacteria (therefore making them one of the best ways to change the microbiota)

Question 5

Why is C. diff so common in hospitals?

Answer 5

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

Question 6

Once C. diff has an entry way to the gut epithelium, what happens?

Answer 6

causese mucosal injury and neuts and RBCs leak into the gut between injured epithelial cells

connective tissue degradation leads to colitis and pseudomembrane formation

Question 7

What is the ONE gut species that has been identified as important?

Answer 7

Bacills subtilis

Question 8

What are probiotics?

Answer 8

bacteria that promote the gut colony to help with digestion, etc

Question 9

How was b. subtilis experimentally proven to be important?

Answer 9

given to a mouse and it protected it from traveler’s diarrhea (aka E. coli)

Question 10

How do commensals protect from intestinal inflammation?

Answer 10

balance of pro and anti-inflammatory immune reactions

some bacteria promote Th cells while others promote Treg cells

Question 11

Which gut bacteria increases levels of FoxP3? (aka Tregs)

Answer 11

B. fragilis

Question 12

What is dysbiosis?

Answer 12

an abnormal microbiota (changed by antibiotics, diet or sleep) can favor pro-inflammatory (Th17 and Th1) over anti-inflammatory (Treg) state

Question 13

What is Inflammatory Bowel Disease/Crohn’s/ulcerative colitis?

Answer 13

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

Question 14

How was IBD determined to be a disease caused by commensals and not autoimmune?

Answer 14

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

Question 15

Which gut bacteria is particularly important in commensal bug diseases like IBD?

Answer 15

B. fragilis (induces Tregs)

Question 16

In addition to IBD, what other disturbances can gut microbes cause?

Answer 16

allergies, autoimmunity, metabolic syndrome

Question 17

Why has a decline in infectious diseases paralleled a rise in immune disorders?

Answer 17

hygiene hypothesis

Question 18

True or false: incidence of allergy is increased in children given antibiotics in the first year of life

Answer 18

TRUE

Question 19

How did science figure out that intestinal microbes can protect from allergy?

Answer 19

had a normal mouse —> gave it antibiotics then exposed it to dust mite allergen (got allergies)

Question 20

Why is a decrease in early exposure to bacteria and infection a risk factor for developing allergy?

Answer 20

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

Question 21

In simpler terms, what is the immunological basis for the hygiene hypothesis?

Answer 21

Th2»Th1 when not exposed to bacteria and viruses

Question 22

How do commensals play a role in allergy?

Answer 22

they regulate Th1 and Th2 responses

Question 23

How can microbiota protect from autoimmune diseases like MS?

Answer 23

exploit B. fragilis to induce Tregs (generates tolerogenic DCs which can tone down the immune system and subdue autoreactivity)

Question 24

How can intestinal microbiota cause metabolic syndrome?

Answer 24

transfer of gut microbiota from TLR5-/- mouse to antibiotic (gut compromised) treated WT, get obese WT mouse

Question 25

True or false: high fat diet induces changes in the microbiota which can promote obesity

Answer 25

TRUE (give microbiota from obese twin to lean twin, make lean twin obese)

Question 26

True or false: gut bacteria from thin humans can protect mice from obesity

Answer 26

TRUE if given low-fat diet (lean-associated microbiota can prevent obesity in mice with obese-associated microbiota. Can only do so much, however, as lean microbiota could not prevent obesity on a high fat diet)

Question 27

True or false: gut microbial dysbiosis is associated with IBD, T2DM, and necrotizing enterocolitis

Answer 27

TRUE

Question 28

What are 4 things that influence gut microbiota?

Answer 28

1) host genetics
2) lifestyle
3) early colonization (ex: birth in hospitals)
4) medical practices (ex: hygiene)

Question 29

What are 3 big causes of dysbiosis?

Answer 29

1) antibiotics
2) diet (especially high fat)
3) early childhood experience (hygiene hypothesis)
4) model of delivery (vaginal vs. cesarian - more allergy with C section babies)

Question 30

What effect does antibiotic treatment have on cancer therapy?

Answer 30

impairs it! (watch mice with antibiotics in their drinking water and their tumor size does not shrink)

Question 31

What are the 5 key points of the lecture?

Answer 31

1) commensals can suppress inflammatory responses and protect from diseases in intestine and other organs
2) protection is mediated by balancing Th1 and Th17 with Treg
3) dysbiosis of gut commensals likely contributes to chronic inflammatory diseases
4) dysbiosis caused by diet, antibiotics, stress, possible early childhood exposure to commensals
5) antibiotics that kill commensals have a NEGATIVE influence on cancer drug effectiveness