The microbiome of the liver Flashcards
How many bacterial species do humans carry?
10 trillion
How does the collective number of bacterial genomes compare to humans?
10:1
How many different species of bacteria/fungi/viruses exist?
> 1000
What did the discovery of the microbiome lead to?
The field of epigenetics
How many bacterial phyla are known?
Over 50
How many bacterial phyla are found in the gut?
6
List the 6 bacterial phyla found in the gut
Bacteroidetes
Firmicutes
Actinobacteria
Proteobacteria
Verrucomicrobia
Fusobacteria
Compare the number of genes found in the human genome and the human microbiome
23 000 genes in human genome
+ 1 000 000 genes in human microbiome
Microbial species and abundance stays the same throughout the GI tract
TRUE or FALSE
FALSE
Microbial species and abundance change over the length of the GI tract
Where are most of the bacteria found in the gut?
In the colon
What happens to the abundance of bacteria as you go further up the GI tract?
Decreases
The more - the microbiota, the better
Diverse
What is a major risk factor for cirrhosis?
Alcohol
Healthy individuals who consume alcohol show evidence of bacterial translocation
The relative abundance of phyla at most sites tends to be consistent across individuals
TRUE or FALSE
TRUE
Where is the composition of microbiota more variable between individuals?
Vaginal microbiota
Which phyla predominate in the colon?
Bacteroidetes
Firmicutes
What is dysbiosis?
Perturbation in composition, function or organisation of the microbiota
Related to various conditions
Which factors contribute to dysbiosis?
Environmental factors
Age
Genetics
What are the main consequences of liver disease?
Hepatic encephalopathy
Ascites
Spontaneous bacterial peritonitis
How do we know that bacteria play an important part in the progression of liver disease?
Patients positive for bacterial DNA in the blood have decreased survival of liver disease
Bacterial population in patients with liver disease is markedly different to controls
What is an important factor about the role of bacteria in liver disease?
The role changes depending on the stage of liver disease
Initially = progression of cirrhosis and fibrosis
Once the patient develops cirrhosis = increases chances of developing hepatic encephalopathy and spontaneous peritonitis
Examplea of how bacterial populations are different in liver disease patients compared to control
Less diversity
Abnormal bacterial species found in the gut - bacteria from mouth found in the liver
Increased population of ammonia-producing bacteria
How is the innate immune system linked to cirrhosis?
PAMPs and DAMPs activate immune cell receptors
These lead to the assembly of the inflammasome
Activates CASP-1 and leads to secretion of cytokines
Which inflammasome is thought to be activated in liver disease?
AIM2 inflammasome
How does cholesterol/ethonal trigger the immune response against the liver?
High cholesterol can trigger hepatocyte steatosis
Ethanol can result in hepatocyte death
These alter the composition of gut microbiota, which results in increased microbial translocation to portal blood and elevated liver exposure to PAMPs
What is a common PRR in immune cells?
TLR4
How was TLR4 used in cirrhosis investigations?
Bile ligation was performed on mice to induce liver cirrhosis
Mice with TLR4 knockout were protected from liver cirrhosis
Antibiotics sterilised the gut = protective. This concretised the role of the innate immune system in fibrosis
How is the survival of cirrhotic patients on prophylaxis?
Improved survival
What are fecal transplants currently used for?
C. difficile
Considering controversial treatment for cirrhosis patients
What are probiotics?
Live microbes
When administered in adequate amounts confer a beneficial health effect on the host
Examples of probiotics
Lactoballicus
Bifidobacterium
List the desirable features a bacteria must have to become a probiotic
Non-pathogenic
Resistant to gastric acid
Produce antibacterial substances
Able to resist antibacterial mechanisms in the gut
Can avoid effects of peristalsis
Resistant to bile acid
What are prebiotics?
Substrates for specific bacteria which influences what grows in the gut
Instead of implanting bacteria directly into the microbiome
What type of gut bacteria are there?
Commensals
Pathogens
What is required for gut health to be maintained?
Balance between commensals and pathogens
What is the problem with growing bacteria found in the gut?
Only 10-20% can be grown in a lab
What is used to identify bacterial species?
16s sequences
Well conserved aspects of bacterial structures
Unique to each species
What are the problems with 16s sequencing?
Bacteria contain more than one 16s ribosomal sequence
16s sequencing does not tell you anything about the bacterial function
Can’t determine the number of genes carried by the bacteria
What technologies help determine microbiota function?
Metabolomics
Metagenomics
Metatranscriptomics
