15 - Microbial Roles in Metabolism Flashcards
Microbiota
Composition of Microrganisms in the human body
- Distributed throughout the body:
- Oral Cavity
- Upper / Lower Respiratory Tract
- Skin
- GI / Internal tissues
- Urethra / Vagina
Types of SCFAs and how are they produced
Dietary Fiber -> fermented by bacteria
produces:
Butyrate
Acetate
Propionate
Name ONE DRUG whose metabolism is presumed ALTERED by the gut microBIOTA
Digoxin, bacteria shown to lower half life -> INCREASE Digoxin
ACETAMINOPHEN -> TOXICITY
- Gut microbiota produces p-cresol
- which competes w/ APAP to be inactivated by SULT
- APAP is inactivated by SULT (sulfotransferase)
-
side metabolism by CYP2E1 produces NAPQI
- NAPQI is TOXIC
-
side metabolism by CYP2E1 produces NAPQI
ID one mechanism by whick one of microbiota metabolites impacts HOST SIGNALING in the body
SCFA’s are sensed by various
Entero-Endocrine GPCRs
which affect/control Insulin Secretion
which will ultimately Negatively affect
GLUCOSE HOMEOSTASIS
How does the gut microbiota’s action on CHOLINE affect
HUMAN HEALTH?
Altered Choline -> TMA -> TMAO
MAY INCREASE CVD RISK
DEVELOPMENT OF ATHEROSCLEROSIS
SCFAs affects on HUMAN HEALTH
Dietary fiber -> SCFAs -> various GPCRs
-
Endocrine B-Cells -> control insulin secretion
- Glucose Homeostasis
-
Adipocytes -> inhibit Adenylate Cycase expression
- low levels of cAMP
- inhibit LIPOLYSIS
- adipocyte METABOLISM
Difference between Microbiome & MicroBIOTA
Microbiome = GENETIC INFO
encoded within all genomes present in the microbiota
MicrobioTA = TA Human Body
composition of microorganisms in the human body
TMAO Functions
Trimethylamine-N-Oxide
gut microbiome ALTERS Choline -> TMA -> TMAO (in liver)
- HIGH LEVELS in BLOOD are associated with:
-
INCREASED risk of major adverse
- CV & Liver Disease
-
INCREASED risk of major adverse
-
Too much TMAO -> reduced Choline Bioavailability
- -> mimick Fatty Liver Disease
What does it mean that microbioTA can be different between INDIVIDUALS or WITHIN AN INDIVIDUAL
over time
-
TAXONOMIC COMPOSITION / RELATIVE ABUNDANCE
- We can see how SIMILAR or DIFFERENT the bacteria is amoungst individuals
-
PRINCIPAL COORDINATE ANALYSIS
- Similar microbiota are closer together
- Oral / Gut / Skin – grouped seperately
- We see how the microbioTA differs within the individual
- Similar microbiota are closer together
What are recent research approaches that allow for the study of microBIOTA affects on HEALTH
NIH Human Microbiome Project
-
HMP1
- Characterization of the microbiomes of human subjects
- at 5 major body sites using:
- 16S rNA Sequencing
- Metagenomic Shotgun Sequencing
- at 5 major body sites using:
- Characterization of the microbiomes of human subjects
-
iHMP
- Characterization of microbiome and human host from three cohorts of microbiome-associated conditions
- using multiple ‘omics technologies
- Characterization of microbiome and human host from three cohorts of microbiome-associated conditions
How does gut microbiota affect BILE ACIDS?
5-10% of Bile acids are BIOTRANSFORMED by gut microbiota
to produce Secondary Bile Acids:
Deoxycholate,
Lithocholate
ligands for nuclear receptors = FXR,
POSITIVE effect on obesity/metabolic syndromes
Microbiome
GENETIC INFORMATION encoded within all genomes present in the MICROBIOTA
- NIH Human Microbiome Project
- WE are finding a lot of evidence that
- human microbiota have an significant impact on our health
What are the primary metabolites PRODUCED or ALTERED by the gut microBIOTA?
- From Complex Carbs that are digested by GUT Microbiota:
-
SCFAs (short chain fatty acids, from FIBER)
- ultimately has NEGATIVE effects
-
Choline (ALTERED -> TMA -> TMAO)
- NEGATIVE effects, risk of CV/Liver disease
-
Bile Acids (specifically SECONDRARY BA’s)
- POSITIVE EFFECTS, inhibits growth of CDIFF spores
-
SCFAs (short chain fatty acids, from FIBER)
What does Gut Microbiota do to Choline?
Choline is ALTERED by gut microbiota -> TMA
In the liver, TMA can be converted to TMAO
