Intestinal microbiome and inflammation

Question 1

What is gastroenteritis?

Answer 1

Inflammation of the stomach and small intestine.
Loss of fluid and solutes form GIT in excess of 500ml/day (only 1%)

Question 2

What are the causes of gastroenteritis?

Answer 2

Viruses, bacteria and parasites.
Can also be caused by stress, intolerance and drugs.

Question 3

What is diarrhoea classified asa?

Answer 3

A change in stool from the norm to be more runny, not necessarily a specific level.

Question 4

What are the processes that lead to gastroenteritis?

Answer 4

Osmosis
Secretion
Motility
Inflammation

Question 5

How does osmosis cause gastroenteritis?

Answer 5

Osmotic potential across the intestinal mucosa is not maintained (osmotic pull into lumen) rather than water being extracted.
Absorption disorders - intolerance e.g. lactose
Acute pancreatitis.
Viral infection - villi blunting, causes loss of absorption.

Question 6

What is osmotic diarrhoea?

Answer 6

When glucose and lactose enter the large intestine they may be fermented by colonic bacteria so that each molecule is degraded to a number of products, increasing the osmolarity even further.
The volume of water transported into the lumen may be too great for the colon to reabsorb it.

Question 7

How does secretory mechanisms lead to gastroenteritis?

Answer 7

Secretions from the small intestine overwhelm the capacity of colonic reabsorption.
Bacterial enterotoxins increase cAMP levels, which inhibits Cl-/Na+ absorption from the intestine, which induces cellular secretion, and inhibits water absorption.
The glucose/amino acid Na+ channels are not affected, so water can enter this way.

Question 8

How else can secretory diarrhoea be caused?

Answer 8

Excessive activation of intrinsic neurons in pathological conditions may also cause secretory diarrhoea.
Some of these neurons release VIP that increases intracellular cyclic-AMP.

Question 9

How does motility cause gastroenteritis?

Answer 9

Water delivery to the colon at a higher rate than can be absorbed.
Bacterial lipid fermentation causes increase in motility.
Parasitic infection e.g. Giardia, can lead to hypermotility

Question 10

How can defective ion transport cause diarrhoea?

Answer 10

Active transport of Na+ is a major determinant of the osmotic transport of water from the lumen into the blood, so inhibitors of Na+ transport will inhibit water transport to cause diarrhoea.
Bile acids inhibit Na+ absorption in the colon if they are not absorbed in the terminal ileum.
Fat malabsorption causes fermentation of lipids in the colon to produce toxins that inhibit Na+ absorption.

Question 11

What is bacterial gastroenteritis?

Answer 11

Caused by E.Coli, C.Diff, and salmonella.

Question 12

What is E.coli?

Answer 12

Produces toxins which adheres to the epithelia and prevents water absorption.

Question 13

What is C.Diff?

Answer 13

This is antibiotic related.
Antibiotics do not kill C.diff, but kills many other bacteria, so there is more room and nutrients for C.diff to proliferate, and causes diarrhoea and dehydration.

Question 14

How does E.Coli cause diarrhoea?

Answer 14

Colonisation: E.coli stick to epithelia.
Produces ETEC enterotoxins, increase intracellular cGMP and cAMP, stop intestinal fluid uptake, increased secretion of water - leading to diarrhoea.

Question 15

How can you quantify bacteria?

Answer 15

Original sample is diluted so there are only a few bacteria in the sample.
Count the CFUs - colony forming units.
Then multiply by the amount it has been diluted to see how much bacteria was in the original sample.
The agar plate with the most original type of bacteria is likely to be the cause of the disease.

Question 16

What is viral gastroenteritis?

Answer 16

Caused by rotavirus or noravirus.
Spread more in winter because more time is spent inside so more susceptible to exposure.

Question 17

What is rotavirus?

Answer 17

RNA virus.
Causes mucosal damage, which means less water is absorbed.
Malabsorption
Enterotoxin which increases secretion.
Reduces glucose co-transport of electrolytes.

Question 18

What is noravirus?

Answer 18

RNA virus
Villi blunting
Malabsorption
Replication in enterocyte.
More water remains in GIT.

Question 19

What is parasitic gastroenteritis?

Answer 19

Caused by giardia parasite.
Often asymptomatic.
Increases gastrointestinal motility - so things aren’t absorbed properly.

Question 20

What is IBD?

Answer 20

Inflammatory bowel disease.
Inflammatory GIT, mainly in the small and large intestines, but can be anywhere.

Question 21

What causes IBD?

Answer 21

Genetic defects
Environment - smoking, diet, medications, microbiota.
Intestinal barrier can have compromised permeability due to goblet cells, paneth cells and from autophagy.
Immune response - cytokines, effector cells and regulatory cells.

Question 22

What is the mechanism in IBD?

Answer 22

The mucosal barrier of the GIT has punctures, segmented, leaky, things leaking through from lamina propria.
Bacteria from microbiome leach into cells, which initiates inflammatory immune response.
Bacteria becomes less diverse and there is less bacteria.

Question 23

What is the genetic causes of IBD?

Answer 23

NOD2 receptor recognises bacteria in the mucosal layer, and signals to immune system to regulate immune response.
In IBD, mutated NOD2 receptor, recognise bacteria but cannot control immune response i.e. to say that bacteria being there is fine.

Question 24

What is UC?

Answer 24

Ulcerative colitis, a form of IBD.
Begins in the rectum extends proximally to involve the entire colon.
Only affects the mucosal layer of epithelium.
Smoking prevents it.

Question 25

What is CD?

Answer 25

Crohn's disease Can affect any part of the GIT, but is usually in the small intestine near the appendix. Transmural inflammation - affects all the epithelial layers. Can cause diabetes, MS, asthma, psoriasis.

Question 26

What is the treament of UC?

Answer 26

Anti-inflammatory therapies. Immunosepressives. Steroids during remission. These dampen the inflammatory response. Colectomy, add stoma, due to localised in colon.

Question 27

What is the treatment for CD?

Answer 27

Diet Antibiotics Immunosuppressives and anti-inflammatory agents. Cannot do colectomy as CD can be anywhere along the GI tract, but could consider segmental resections.

Question 28

What are the microorganisms in the microbiome?

Answer 28

Bacteria Phages Archaea Fungi

Question 29

What are the functions of the intestinal microbiome?

Answer 29

Pathogen resistance/ antimicrobial action Nutrient metabolism Immunomodulation Colonic cell maintenance Mental well being

Question 30

Where is the microbiome?

Answer 30

More bacteria as you go distally down colon as environment is more favourable for bacteria in colon, higher pH, less bacteria to suppress bacterial growth, so more growth. No oxygen in colon - anaerobic bacteria can grow.

Question 31

Where does bacteria grow?

Answer 31

Grow in the digesta of the colon, in the lumen, or stick to the mucosa and grow niches there.

Question 32

What is the antimicrobial action of the microbiome?

Answer 32

Bacteria in microbiome take up space and nutrients - colonisation, stops new bacteria being produced as can't grow - colonisation resistance. Taking anti-microbials removes the bacteria so new bacteria can grow.

Question 33

What is the immunomodulation of the microbiome?

Answer 33

Acquire mothers microbiome during birth, exposed to more bacteria throughout life, immune system is learning that some bacteria is ok so is not responsive. Children born by c-section, or only eat certain food, or not exposed to bacteria, immune system is not trained, so immune response and inflammation - IBD.

Question 34

How is the microbiome linked to mental wellbeing?

Answer 34

Neurotransmitters and hormones produced by microbiome, influence feelings and depression.

Question 35

What are the bacteria in the microbiome?

Answer 35

Bacillota phyla and Bacteriodota phyla.

Question 36

How is the composition of bacteria in the microbiome altered?

Answer 36

Diet Medications Age - acquire microbiome as you grow, stable from age 15, then declines in composition later in life.

Question 37

What are the types of enterotypes?

Answer 37

Bacteriodes enterotype Prevotella enterotype Ruminococcus enterotype Enterotype can be changed through diet, and not directly causing disease. Can also be continuous between populations.

Question 38

How can enterotypes be a good biomarker?

Answer 38

Can be used to predict the likelihood of acquiring a disease and the response to treatment.

Question 39

What is faecalibacterium prausnitzii?

Answer 39

Faecalibacterium prausnitzii produces uterate - short chain fatty acid, for maintaining mucosa and neurotransmission. It also metabolises fructo-oligosaccharides, pectin and inulin, which the digestive system cannot digest. In IBD it is absent.

Question 40

What is akkermansia muciniphilia?

Answer 40

Sticks to mucosal surface and degrades mucin (mucous like compound that separates bacteria from host cells). Metabolites are acetate and propionate Linked to obesity and is reduced in IBD.

Question 41

What is the importantance of short chain fatty acids in energy balance?

Answer 41

Increased oxygen uptake and blood flow. Function as an energy source. Improved barrier function.

Question 42

What is the importance of SCFAs in HDAC inhibition?

Answer 42

Mucus production and protection. Oxidative stress reduction. NF-kB suppression and Treg differentiation. Apoptosis, proliferation and differentiation.

Question 43

What is the importance of SCFAs in gene-protein reaction activation?

Answer 43

Chemokine and cytokine production. Adhesion molecule and chemotaxis suppression. NF-kB suppression and Treg differentiation. Apoptosis, proliferation and differentiation.

Question 44

What are the SCFAs in the microbiome?

Answer 44

Short Chain Fatty acids Butyrate, propionate, acetate.

Question 45

What is a healthy microbiome?

Answer 45

Undertakes its function Resistant to perturbation - stable, doesn’t let new bacteria into the community Diverse and rich Different for different people Eubiosis

Question 47

What is eubiosis?

Answer 47

The ecosystem serves the host. It is a state of balanced equilibrium.

Question 48

What is dysbiosis?

Answer 48

The community of bacteria changes and the ecosystem is detrimental to the host.

Question 49

How is dysbiosis related to IBD?

Answer 49

Eubiosis - then two hit trigger - genetics, damage to mucosa, change in diet etc, causes dysbiosis and IBD.

Question 50

What are prebiotics?

Answer 50

Food that the body cant digest, but the bacteria are nourished by it e.g. fibrous vegetables , pulses and grains.

Question 51

What are probiotics?

Answer 51

Contain living organisms, bacteria is directly introduced into microbiome. e.g. yoghurts

Question 52

What is FMT?

Answer 52

Faecal microbial transplantation - transplant whole microbiome from donor into patient, replaces their microbiome.

Question 53

Why do probiotics not work?

Answer 53

Microbiome stops introduction of bacteria So bacteria that is consumed from probiotics is excreted out. The stomach will also kill bacteria.

Question 54

What are the uses of FMT?

Answer 54

Faecal material from healthy people, to transfer healthy bacteria. e.g. for UC, who have lost the ability to use the toilet, but FMT can cure this. e.g. for C.Diff, antibiotics would make it worse, as removes healthy bacteria, but FMT if effective.

Question 55

What can FMT transfer?

Answer 55

SCFAs improve epithelium integrity - unknown if transfer of SCFA or bacteria-producing SCFAs. Bile salts Viruses Enhanced efficacy when prepared in an anaerobic environment.

Question 56

What are the limitations of FMT?

Answer 56

Invasive delivery routes - colonoscopy. Not sure what a healthy microbiome is, or how FMT works. Hard to regulate and produce. Risk of pathogenic transmission. And donors should have strict criteria.