W4 19 gastrointestinal infections

Question 1

Structure of the gut - gut microbiome is complex!

Answer 1

Stomach
Duodenum
Jejunum
Ileum
Colon/large intestine

Question 2

What influences whether the balance between the microbes and the host are healthy or pathological?

Answer 2

Genes, food, drugs

Question 3

What is the composition of the gut microbiome in a healthy situation?

Answer 3

In health, the composition of the gut microbiome is associated with:
- a higher mucus layer thickness
- the production of Antimicrobial signals
- different short-chain fatty acids like butyrate and propionate = essential for survival of certain bacteria in the gut and important for energy, metabolism and digestion

Question 4

What does the healthy composition of the gut microbiome maintain in the gut?

Answer 4

• contributes to reduce food intake and improve glucose metabolism
• maintain appropriate immune defence
• maintain anaerobic condition in the gut lumen

Question 5

What happens if the balance gets disrupted in the gut microbiome, eg during metabolic disorders?

Answer 5

Changes in the gut microbiome are linked with:
- a lower mucus thickness
- decreased Antimicrobial defence
- change in short-fatty acid production - decreased butyrate and propionate production

Question 6

What can decrease butyrate and propionate production cause?

Answer 6

Inflammation, higher blood glucose levels and a wide range of disease

Question 7

What do the changes in the microbial environment and metabolites cause? (good image pg212)

Answer 7

Induce a leakage of pathogen associated molecule patterns (PAMPs) such as the lipopolysaccharide (LPS) that are increased in the blood, and trigger low-grade inflammation

Question 8

What diseases can cure when the gut microbiotia gets out of balance?

Answer 8

Obesity
Metabolic syndrome
C. difficile infection
Colorectal cancer
IBD
Psychiatric disorders

Question 9

What are some physical and chemical host defences in the GIT?

Answer 9

Enzymes in saliva and small bowel
Acidic environment of stomach - low pH only allows few bacteria to survive
Bile in small bowel
Physical movement of gut preventing close approximation with intestinal wall
Mucosa lining and mucin

Question 10

What are some immune system/internal defences from the host?

Answer 10

Secreted IgA
Peyers patches

Question 11

What is gastroenteritis and what is it caused by?

Answer 11

Most common infections, by bacteria, viruses or parasites
Mainly caused by contaminated crops or drinking water, or food poisoning

Question 12

Symptoms of gastroenteritis

Answer 12

Loss of aperture
Fever
Nausea/vomiting
Diarrhoea
Abdominal cramps
- leads to dehydration

Question 13

Give some examples of the viruses, bacteria, toxins and parasites causing acute gastroenteritis, and food/travel associated diarrhoea

Answer 13

Viral: rotavirus, norovirus
Bacterial: E. coli, salmonella
Toxins: C. difficile, Staph aureus
Parasitic: Cryptosporidium parvum

Question 14

How does food and travel-associated diarrhoea occur?

Answer 14

Spread from contaminated food or water
(Same organisms as before causing)

Question 15

What is salmonella and what can it cause?

Answer 15

Major cause of food poisoning (chicken, eggs)
Most common = S enteritidis- usually self-limiting diarrhoeal illness. Not pleasant but not serious.
Most severe = S typhi/S paratyphi. Typhoid and paratyphoid causes severe life-threatening sepsis, requires antibiotic treatment - ciprofloxacin or ceftriaxone

Question 16

How is salmonella diagnosed?

Answer 16

Stool culture - on agar. Black colonies formed
Blood cultures- high risk infections

Question 17

What is Helicobacter pylori?

Answer 17

A pathogen responsible for gastritis and peptic ulcers, and a risk factor for gastric cancer

Question 18

What in the oral cavity might function as a reservoir for H pylori?

Answer 18

Periodontal pockets (from chronic perio)

Question 19

Give some properties of H pylori

Answer 19

Gram negative, spiral, curved bacillus
Strict growth requirements
Microaerophillic - tolerates oxygen at a lower than atmospheric concentration
Motile - has flagella
Urease positive

Question 20

What does being urease positive mean for H pylori?

Answer 20

Normally, contact with the stomach acid keeps the mucin lining the epithelial cell layer in a spongy gel-like state, which is impermeable to the bacterium.
However H pylori released urease which neutralises the stomach acid, causing the mucin to liquify so that the bacterium can swim through it.

Question 21

How is H pylori tranmitted?

Answer 21

Either oral-oral or faecal-oral
Incubation period abt 5-10 days

Question 22

What does the H pylori infection cause?

Answer 22

Bacterial infection causes chronic gastritis, and duodenal ulcer disease
Inflammatory response

Question 23

What are the clinical features of H pylori infection?

Answer 23

Epigastric oain
Nausea, vomiting
Haematemesis - vomiting blood
Blood-stained or dark stools
Symptoms usually resolve despite persistence of infection

Question 24

How can you diagnose H pylori infection?

Answer 24

Often requires endoscopy and biopsy
Culture
Diagnostic kits - urease breath kits, test of biopsy sample
Serology - test the presence of antibodies in blood

Question 25

Does everyone with H pylori infection get ulcers?

Answer 25

No

Question 26

How do you manage/get rid of a H pylori infection (it’s not easy)?

Answer 26

Combination therapy:
2 antibiotics from: amoxicillin, metronidazole, clarithromycin, tetracycline
Proton pump inhibitor: omeprazole, lansoprazole

Question 27

Properties of Clostridium difficile infection

Answer 27

Gram positive, anaerobic bacillus
Endoscope former

Question 28

What happens when conditions are bad for C. difficile?

Answer 28

Eg in an oxygen rich environment with no nutrients and is starving, it will start to form a spore as a survival mechanism (not fungal spore).
(It can survive oxygen, high temperatures, disinfectants, antibiotics etc)

Question 29

What happens to C. difficile when the conditions are better again for it?

Answer 29

In our gut there are certain signals that the spore can sense and germinate and become a living growing toxin-producing C. difficile cell again.

Question 30

What happens in a lifecycle of C. difficile infection?

Answer 30

It grows in the vegetative state, divides by binary fission, replicates, makes toxins
SPORES CRITICAL FOR DISEASE TRANSMISSIN!

Question 31

How can the transmissive spores enter the body?

Answer 31

Spores can survive in soil, door handles etc
Easy to ingest
Travel through the stomach, get into the intestine and get cues to become vegetative cells again.

Question 32

What do the toxins produced by vegetative cells do?

Answer 32

Toxins attack our cells
Cause diarrhoea - leads to pseudomembranous colitis
If we have a healthy gut microbiome the bacteria won’t germinate and cause disease

Question 33

How can C. difficile be antibiotic induced?

Answer 33

If someone is already in a dysbiosis state, broad spectrum antibiotics will be given, killing many types of bacteria even good bacteria. So C. difficile will start to colonise, produce toxins and cause disease.

Question 34

What are the clinical features of C. difficile infection?

Answer 34

Can range from mild disease to bad sickness:
- mild self limiting diarrhoea
- pseudomembranous colitis
- toxic megacolon
- abdominal cramping
- fever
Might be asymptomatic carriers

Question 35

What different ways can C. difficile be diagnosed?

Answer 35

Chom-ID plate (time consuming)
Cell culture to determine cytotoxicity (img pg220) (time consuming)
Quick test - apply stool sample. Follow up with ELISA or PCR

Question 36

What do the quick test for C. difficile results mean? (Pg221)

Answer 36

1 line present means test is positive for antigen and bacteria is present, but no toxin - some strains don’t produce the toxin in which case pt has something else, or the stain has toxin genes but hasn’t yet produced it
2 lines mean it is present and producing the toxin
No lines means it is negative and the bacteria is not present

Question 37

How do we manage patients with C. difficile infection? - first line?

Answer 37

Isolate the patient to stop spread
Antibiotic therapy: metronidazole (might not work used in milder cases), vancomycin (soused in more severe but resistant strains are a worry), fiadaxomicin (works well but exp)
(Prevention better than cure tho)

Question 38

What are some alternative to antibiotic therapies for C. difficile infection?

Answer 38

Prebiotics and probiotics
Absorbents for toxins - to eliminate them from the gut
Faecal transplants
Immunotherapy - active or passive immunisation