Microbiome

Question 1

Microbiome

Answer 1

The entire community of microbes (and their genes) that live in and on the human body

Question 2

What is Akkermansia muciniphila involved in?

Answer 2

Preventing mice from being overweight

Question 3

TMAO

Answer 3

Trimethylamine N-oxide previously shown to accelerate atherosclerosis
Phosphatidylcholine is converted to TMAO only when microbes exist in the gut
Vegans produced less TMAO when given phosphatidylcholine (their gut microbes did not produce it)

Question 4

DMB

Answer 4

Dimethyl butanol
Found in several foods (olive oil, balsamic vinegar, grape seed oil)
Blocks the conversion of choline to TMA

Question 5

Germ free mice display….

Answer 5

Increased motor activity and reduced anxiety

Question 6

Why do we use fecal transplants?

Answer 6

To treat recurrent C diff infections

They are much more effective than antibiotics

Question 7

Early studies looking at drug metabolism by the gut microbiome observed..

Answer 7

Biotransformation of drugs after incubation of intestinal contents ex vivo
Biotransformation was eliminated when pre-treated with antibiotics or when looking at germ free mice

Question 8

Digoxin

Answer 8

Cardiac glycoside used to treat heart function abnormalities

Binds the Na/K ATPase transporter in cardiac myocytes

Question 9

How is digoxin inactivated?

Answer 9

Inactivated through chemical reduction to dihydrodigoxin in some patients
Inactive form removed when given antibiotics
Reduction/inactivation requires specific strain of E. lenta (DSM2243)
Reduction rate is increased when in the presence of microbiome community

Question 10

Arginine and digoxin

Answer 10

Stimulates E. lenta growth BUT lowers % reduction of digoxin

Hypothesis is that Arg is needed for microbe growth, but when it is present you dont need to reduce the drugs

Question 11

Irinotecan

Answer 11

Chemotherapeutic for colorectal cancer

Given intravenously in inactive form (pro-drug)

Question 12

Irinotecan metabolism and excretion

Answer 12

Given intravenously in inactive form (pro-drug)
Metabolized by carboxylesterases in tissues and serum into active form (SN-38)
SN-38 glucuronidated in the liver to SN-38-G and is excreted as bile into intestinal lumen

Question 13

What does the microbiome do to irinotecan?

Answer 13

Conversion of SN38-G back to SN-38 in the intestine via microbial beta-glucuronidase
Results in toxic levels and severe diarrhea

Question 14

How do you eliminate microbial effects on irinotecan?

Answer 14

Give inhibitor 1
Targets the microbial beta-glucuronidase
Stops the reactivation