Lecture 14 The Gastrointestinal System PT1 - Structure & Microorganisms

Question 1

How does our gut microbiota help protect against infection

Answer 1

– Outcompete invaders for nutrients
– Reduce availability of attachment
sites
– Produce antimicrobial peptides
e.g. bacteriocins, colicins
– Stimulate host cells to produce
anti-microbial peptides
– Immune regulation
– Maintain anaerobic environment

Question 2

Other GIT Defence Mechanisms

Answer 2

– Acidity in stomach pH 4: limits
organisms reaching small intestine
– Pancreatic enzymes/juices
– Bile from liver via gall bladder
– Intestinal motility: peristalsis
– Mucosal villous lining: protective,
antimicrobial
– GIT immune response

Question 3

Transmission of Microbial Diseases of the GIT

Answer 3

1. Via common vehicles – Water / Food
   * Contaminated with microorganisms and/or preformed toxin
   * E.g. Salmonella, botulism
2. Faecal/Oral route
   * Spread from person-to-person
   * Shed then ingested faecal microbes
   * E.g. Typhoid, Polio

Question 4

Food poisoning – Major cause of gastrointestinal disease
(infection vs intoxication)

Answer 4

• INFECTION: microbe is ingested, colonises the GIT, then replicates
  and can cause disruption to the lining of the GIT, eg. Salmonella
  gastroenteritis
• INTOXICATION: bacteria produce toxins in the food before it is
  ingested eg. botulism, Staphylococcus aureus food poisoning

Question 5

Non-diarrhoeal vs Diarrhoeal GIT Microbial Disease

Answer 5

Examples

Non-diarrhoeal disease:
* Botulism: Clostridium botulinum (LT14)
* Typhoid fever: Salmonella enterica serovar typhi (LT14)
* Polio: poliovirus (LT15)

Diarrhoeal disease:
* Amoebic dysentery: Entamoeba histolytica (protist) (LT15)
* Giardiasis: Giardia intestinalis (protist) (LT15)
* Gastroenteritis: bacterial vs viral: Salmonella vs norovirus (LT15)

Question 6

Botulism: Clostridium botulinum

Answer 6

Toxigenic C. botulinum: Gram +ve, anaerobe,
endospore former

Transmission:
* Infection: consumption of food/water
contaminated with endospores of toxigenic
strains of C. botulinum > germinate and
produce toxin in gut
* Intoxication: consumption of food
contaminated with preformed toxin

Impact low due to good food hygiene practices:
Aust: <10 cases in last 5 years
Around110 cases/yr in US

Question 7

Botulism: Symptoms

Answer 7

Bacteria produce a neurotoxin – causes paralysis
Symptoms result from muscle paralysis caused by the
toxin produced by the bacteria, eg. difficulty swallowing,
difficulty breathing, muscle weakness, double vision,
slurred speech
Additionally, symptoms in foodborne botulism can include
vomiting, nausea, stomach pain, diarrhea
For foodborne botulism, symptoms occur within 12-72
hours of toxin ingestion
If untreated, up to 5% of patients will die
(respiratory/cardiac failure) within a few days

Question 8

Botulism: Clostridium botulinum virulence mechanisms

Answer 8

AB Neurotoxin – extremely potent toxin
- Protease that selectively cleaves synaptic proteins, prevents release of
neurotransmitter acetylcholine > muscles cannot contract
- Spore formation (survival), ability to germinate and metabolise in GIT

Question 9

Botulism: Clostridium botulinum pathogenesis

Answer 9

Ingest toxin directly OR resistant endospores (eg. infant botulinum)
* low pH of stomach triggers spore germination
* vegetative cells produce toxin in GIT, released on cell lysis

Toxin passes through GIT lining and enters bloodstream
* targets neuromuscular junction
* toxin endocytosed into neuronal cells
* affects synaptic proteins to prevent acetylcholine release
* muscle paralysis

Question 10

Botulism: Clostridium botulinum diagnosis and treatment

Answer 10

Diagnosis:
 Symptoms – muscle weakness, drooping eyelids
 Test for toxin in serum/stool/food
 Culture C. botulinum from stool or food

Treatment:
 Antitoxin; botulism immune globulin to treat infants
 Induced vomiting, enema
 Mechanical ventilation to assist breathing

Question 11

non + diarrhoeal (salmonella?)

Answer 11

Non-diarrhoeal:
1. Salmonella enterica subspecies enterica serovar typhi
* Typhoid fever
2. Salmonella enterica subspecies enterica serovar paratyphi
* Paratyphoid fever (similar to typhoid, less severe, less common)

Diarrhoeal disease:
1. Salmonella enterica subspecies enterica (non-typhoidal serovars)
* Gastroenteritis (Salmonellosis)
* Undercooked poultry, meat, egg etc

Question 12

typhoid Fever: Salmonella enterica serovar typhi

Answer 12

Salmonella enterica subspecies enterica serovar typhi: invasive strain;
Gram-ve, facultative Enterobacteriaceae, intracellular pathogen

Transmission:
* Humans only known carriers of Salmonella enterica serovar typhi
* Consumption of food/water contaminated with human faeces
* Person-to-person contact

Impact:
* 9 million infected/yr, ~110,000 deaths globally (WHO 2019 data)
* Risk where populations lack clean water and adequate sanitation
* Priority infection: WHO/Gates Foundation ‘Coalition against Typhoid’

Question 13

Typhoid Fever: Salmonella enterica serovar typhi: diagnosis and symptoms

Answer 13

Symptoms:
* Fever, rash (‘rose spots’), weakness
* Stomach pains, severe headache
* If untreated can result in death (intestinal hemorrhage/
perforation, sepsis)

Diagnosis:
* Culture from stool
* Culture from a normally sterile site (blood or bone marrow:
100% specificity)
* Molecular testing (PCR, whole genome sequencing)
* Serological tests (rapid, lower sensitivity/specificity)

Question 14

Typhoid Fever: Salmonella enterica serovar typhi: treatment and control

Answer 14

Treatment:
* Antibiotics
* Multi-drug resistance an increasing problem
* In few countries up to 70% isolates XDR (mostly ~10%)
Control:
* Sanitation, hand washing
* Travel advice: “Boil it, cook it, peel it, or forget it”
* Vaccine: oral (live attenuated) or injection (purified
antigen)
* These vaccines do not provide long-lasting immunity

Question 15

Salmonella typhi virulence mechanisms

Answer 15

– Adheres to SI: specialised fimbriae
– Invades SI via M cells: flagellin
– Can then spread to lymphoid tissue,
blood, liver and gall bladder

Pathogenicity islands:
– Mobile genetic elements on the chromosome,
encode multiple virulence genes
– E.g. secretion systems
– SPI-1 (pathogenicity island): invasion of
non-phagocytic cells

Question 16

Salmonella typhi virulence mechanisms detail

Answer 16

Evades immune system:
Polysaccharide capsule: Vi antigen:
* shields O antigen (LPS) from antibodies
* intracellular pathogen: survives in
macrophages, inhibits phagocytosis

Damages host:
Typhoid toxin produced intracellularly
AB toxin -> interferes with immune cell function
-> Typhoid fever symptom development
Chronic carriage linked to gall bladder cancer

Question 17

Q: What are the major sections of the gastrointestinal tract (GIT)?

Answer 17

A: The GIT includes the esophagus, stomach, small intestine (duodenum, jejunum, ileum), large intestine (caecum, colon, rectum), and anus​.

Question 18

Q: What are the functions of the GIT?

Answer 18

A: Digestion, nutrient absorption, and waste excretion.

Question 19

Q: Name two diseases associated with the gastrointestinal tract.

Answer 19

A: Botulism (non-diarrheal, caused by Clostridium botulinum) and Typhoid Fever (caused by Salmonella enterica serovar typhi)​​.

Question 20

Q: Where are the largest number of microbes found in the GIT?

Answer 20

A: The large intestine (LI)​.

Question 21

Q: How does the gut microbiota differ between the small intestine (SI) and large intestine (LI)?

Answer 21

A: The small intestine has fewer microbes due to its fast transit time and acidic environment, while the large intestine has more microbes because of the slower transit time and anaerobic environment​​.

Question 22

Q: How does the normal gut microbiota protect against infection?

Answer 22

A: It outcompetes pathogens for nutrients and attachment sites, produces antimicrobial substances (e.g., bacteriocins), maintains a healthy pH and oxygen environment, and supports the immune system​​.

Question 23

Q: What can happen when there is a disruption in the gut microbiota (dysbiosis)?

Answer 23

A: Dysbiosis can lead to an increased risk of infection, inflammation, and diseases like inflammatory bowel disease (IBD)​.

Question 24

Q: What is the difference between bacterial, viral, and protist infections in the GIT?

Answer 24

A:
Bacterial infections (e.g., Salmonella): Often cause gastroenteritis, resulting in inflammation, diarrhea, and abdominal pain.

Viral infections (e.g., norovirus): Lead to viral gastroenteritis with symptoms like vomiting and watery diarrhea.

Protist infections (e.g., Giardia): Can cause giardiasis, leading to prolonged diarrhea and malabsorption​.

Question 25

Q: What are the symptoms of non-diarrheal infections like botulism and typhoid fever?

Answer 25

A:
Botulism: Muscle paralysis, difficulty swallowing, double vision, and difficulty breathing due to neurotoxin effects​.
Typhoid Fever: Fever, weakness, rash, and headache​​.

Question 26

Q: How are gastrointestinal diseases like typhoid fever and botulism transmitted?

Answer 26

A:
Typhoid fever: Spread via contaminated food or water (faecal-oral route)​.
Botulism: Spread by ingestion of food contaminated with botulinum spores or preformed toxin​.

Question 27

Q: What are key virulence factors of Salmonella typhi?

Answer 27

A:
Specialized fimbriae for adherence to the intestine.
Invades non-phagocytic cells via pathogenicity islands (SPI-1).
Vi antigen: Polysaccharide capsule that evades immune detection​​

Question 28

Q: How is botulism diagnosed and treated?

Answer 28

Diagnosis: Based on symptoms (muscle paralysis), testing for toxin in stool or food.
Treatment: Antitoxin, mechanical ventilation, and induced vomiting​.

Question 29

Q: What measures can prevent typhoid fever?

Answer 29

A: Sanitation, handwashing, and vaccination (oral or injected vaccines)​.

Question 30

Q: What natural defenses protect the gastrointestinal tract from infection?

Answer 30

A:
Acidity in the stomach (low pH kills microbes).
Pancreatic enzymes and bile (digest and neutralize pathogens).
Peristalsis (movement of the GIT flushes out microbes).
Mucosal lining (secretes antimicrobial substances)​.

Question 31

Q: How does diet affect the composition of the gut microbiota?

Answer 31

A high-fiber diet supports a diverse and healthy microbiota, while a low-fiber, high-fat diet can lead to dysbiosis​.

Question 32

Q: What are the metabolic products of microbiota fermentation of fiber?

Answer 32

A: Short-chain fatty acids (SCFAs), such as butyrate, acetate, and propionate, which support gut health​.

Question 33

1. Why are there more microbes in the large intestine compared to the rest of the GI tract?

Answer 33

A:
Slow transit time in the large intestine allows more colonization.
Neutral pH and anaerobic conditions support diverse microbial growth.
More nutrients available from undigested food.

Question 34

2. What are the main causes of person-to-person spread of gastrointestinal diseases caused by microbes?

Answer 34

A:
Faecal-oral transmission through contaminated food, water, or surfaces.
Poor hygiene, like not washing hands.
Direct contact with infected individuals or shared environments (e.g., bathrooms).

Question 35

3. Explain how botulism could be both an infection and an intoxication.

Answer 35

A:
Infection: C. botulinum bacteria grow in the body (e.g., infant or wound botulism), producing toxin in vivo.
Intoxication: Ingestion of preformed toxin in contaminated food (foodborne botulism).

Question 36

4. Why did Typhoid Mary not develop symptoms of typhoid fever?

Answer 36

A:
Asymptomatic carrier: Mary harbored Salmonella typhi in her gallbladder, but her immune system controlled the infection without causing symptoms.
She spread the bacteria through food she prepared, even though she didn’t feel ill.

Question 37

5. Describe the intracellular activity of Salmonella typhi.

Answer 37

A:
Attachment: Uses fimbriae to attach to M cells in the intestines.
Invasion: Injects effector proteins via a type III secretion system, inducing endocytosis.
Survival: Forms a Salmonella-containing vacuole (SCV) to survive and replicate inside host cells.
Spread: Invades macrophages and spreads to organs like the liver and gallbladder.