Microbiome Flashcards
The human microbiome includes what? (3)
Prokaryotes
Eukaryotes
Viruses
Different in number of bacterial genes vs. human genes?
100:1
Different in number of microbial cells vs. human cells?
Same number
7 diseases that involve the microbiome?
- Obesity
- Inflammatory bowel disease
- Cancer
- Atherosclerosis
- Rheumatoid Arthritis
- Psoriasis
- Gut-Brain Axis (behaviour/mental illnesses)
4 factors that shape the gut community?
Host genetics
Food
Microbial Exposures
Pharmaceuticals
Difference between microbiomics vs. traditional microbiology?
Microbiology : study a single species
Microbiomics : analysis of entire community, skip isolation of bacteria
What is the leptin gene useful for?
satisfy cravings, inhibits desire to eat
When knocking out the leptin gene in mice, what happens to the bacteria content of Akk. muciniphila?
It decreases
When introducing a high fat diet to mice, what happens to bacteria content?
Decreases
What happens to fat mass gain in mice when you add a probiotic to an already high fat diet?
What about normal diet?
High fat : probiotic decreases fat mass gain
Normal : not much difference
What molecule accelerate atherosclerosis?
TMAO : Trimethylamine N-oxide
How is TMAO produced?
When can phospha be converted to TMAO
Which enzyme is involved?
Phosphatidylcholine (from diet) converted to choline, then to TMA in gut flora (TMA lyase), then to TMAO in liver
Can only be converted when microbes exist in the gut
What reduces TMAO levels? (2)
Antibiotics
Vegan diet
What has shown to block TMA lyase? Where is this molecule found?
DMB (dimethyl butanol)
Found in foods (olive oil, balsamic vinegar, grape seed oil)
Abnormal gut function can lead to what type of CNS changes?
Stress/disease:
- Behavior, cognition, emotion, nociception
- Levels of inflammatory cells/mediators
- Intestinal dysbiosis
How are germ free mice different from normal mice?
Locomotor activity increased
Anxiety decreased
What is more effective in curing C. Difficile infection : fecal transplants or vancomycin antibiotic?
Fecal transplant
What did early studies on drug metabolism show in regard to ex vivo drugs?
How was this eliminated?
Ex vivo : incubation of drugs in stool can cause biotransformation into bacteria.
Biotransformation eliminated when pre-treating with antibiotics and germ-free mice.
Name a drug involved in converting prodrug to active metabolite
prontosil
Prontosil is an ________ against _______ infections
Antibacterial
Streptococcal
Does prontosil have antibacterial effects in vitro?
No
Prontosil has reduced activity when… ?
Pre-treating with other antibiotics
Prontosil is converted to ________ by which enzyme?
Sulfanilamide
Azoreductase
Name a drug involved in converting active metabolite to inactive metaoblite
Digoxin
Digoxin is a _____ _____ used to treat… ?
Cardiac glycoside
Heart function abnormalities
Digoxin binds to what? where?
human Na+/K+ ATPase transporter
Cardiac myocytes
When is digoxin inactivated? Which strain is necessary?
Chemical reduction to dihydrodigoxin Eggerthella Lenta (DSM2243)
How to remove inactive form of digoxin?
Antibiotics
What happens to reduction rate of digoxin when E.Lenta is in the presence of gut microbia?
Reduction increases, better metabolism
Effects of arginine on E.Lenta and digoxin metabolism?
Increases bacteria
Digoxin metabolism decreases
Name a drug that converts drug/metabolite into toxic metabolite
Irinotecan
Irinotecan is a ________ for what?
Chemotherapeutic
Colorectal cancer
How is irinotecan given and in which form?
IV
Inactive form
How is Irinotecan metabolized? Where?(2) Into which form?
By carboxylesterases
Tissues and serum
Active form (SN-38)
How is SN-38 excreted?
Glucuronidated in liver to SN-38-G
Excreted as bile into intestinal lumen
What effect does beta-glucuronidase have on SN-38-G?
Converts SN-38-G back to SN-38 in the intestine
Toxic levels of SN-38, diarrhea
How can you treat toxic levels of SN-38 by beta-glucuronidase? (2)
Antibiotics
Target BG directly with inhibitor
