The microbiome of the liver

Question 1

How many bacterial species do humans carry?

Answer 1

10 trillion

Question 2

How does the collective number of bacterial genomes compare to humans?

Answer 2

10:1

Question 3

How many different species of bacteria/fungi/viruses exist?

Answer 3

> 1000

Question 4

What did the discovery of the microbiome lead to?

Answer 4

The field of epigenetics

Question 5

How many bacterial phyla are known?

Answer 5

Over 50

Question 6

How many bacterial phyla are found in the gut?

Answer 6

6

Question 7

List the 6 bacterial phyla found in the gut

Answer 7

Bacteroidetes

Firmicutes

Actinobacteria

Proteobacteria

Verrucomicrobia

Fusobacteria

Question 8

Compare the number of genes found in the human genome and the human microbiome

Answer 8

23 000 genes in human genome

+ 1 000 000 genes in human microbiome

Question 9

Microbial species and abundance stays the same throughout the GI tract

TRUE or FALSE

Answer 9

FALSE

Microbial species and abundance change over the length of the GI tract

Question 10

Where are most of the bacteria found in the gut?

Answer 10

In the colon

Question 11

What happens to the abundance of bacteria as you go further up the GI tract?

Answer 11

Decreases

Question 12

The more - the microbiota, the better

Answer 12

Diverse

Question 13

What is a major risk factor for cirrhosis?

Answer 13

Alcohol

Healthy individuals who consume alcohol show evidence of bacterial translocation

Question 14

The relative abundance of phyla at most sites tends to be consistent across individuals

TRUE or FALSE

Answer 14

TRUE

Question 15

Where is the composition of microbiota more variable between individuals?

Answer 15

Vaginal microbiota

Question 16

Which phyla predominate in the colon?

Answer 16

Bacteroidetes

Firmicutes

Question 17

What is dysbiosis?

Answer 17

Perturbation in composition, function or organisation of the microbiota

Related to various conditions

Question 18

Which factors contribute to dysbiosis?

Answer 18

Environmental factors

Age

Genetics

Question 19

What are the main consequences of liver disease?

Answer 19

Hepatic encephalopathy

Ascites

Spontaneous bacterial peritonitis

Question 20

How do we know that bacteria play an important part in the progression of liver disease?

Answer 20

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

Question 21

What is an important factor about the role of bacteria in liver disease?

Answer 21

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

Question 22

Examplea of how bacterial populations are different in liver disease patients compared to control

Answer 22

Less diversity

Abnormal bacterial species found in the gut - bacteria from mouth found in the liver

Increased population of ammonia-producing bacteria

Question 23

How is the innate immune system linked to cirrhosis?

Answer 23

PAMPs and DAMPs activate immune cell receptors

These lead to the assembly of the inflammasome

Activates CASP-1 and leads to secretion of cytokines

Question 24

Which inflammasome is thought to be activated in liver disease?

Answer 24

AIM2 inflammasome

Question 25

How does cholesterol/ethonal trigger the immune response against the liver?

Answer 25

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

Question 26

What is a common PRR in immune cells?

Answer 26

TLR4

Question 27

How was TLR4 used in cirrhosis investigations?

Answer 27

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

Question 28

How is the survival of cirrhotic patients on prophylaxis?

Answer 28

Improved survival

Question 29

What are fecal transplants currently used for?

Answer 29

C. difficile

Considering controversial treatment for cirrhosis patients

Question 30

What are probiotics?

Answer 30

Live microbes

When administered in adequate amounts confer a beneficial health effect on the host

Question 31

Examples of probiotics

Answer 31

Lactoballicus

Bifidobacterium

Question 32

List the desirable features a bacteria must have to become a probiotic

Answer 32

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

Question 33

What are prebiotics?

Answer 33

Substrates for specific bacteria which influences what grows in the gut

Instead of implanting bacteria directly into the microbiome

Question 34

What type of gut bacteria are there?

Answer 34

Commensals

Pathogens

Question 35

What is required for gut health to be maintained?

Answer 35

Balance between commensals and pathogens

Question 36

What is the problem with growing bacteria found in the gut?

Answer 36

Only 10-20% can be grown in a lab

Question 37

What is used to identify bacterial species?

Answer 37

16s sequences

Well conserved aspects of bacterial structures

Unique to each species

Question 38

What are the problems with 16s sequencing?

Answer 38

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

Question 39

What technologies help determine microbiota function?

Answer 39

Metabolomics

Metagenomics

Metatranscriptomics