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TAS Gastroenterology > Genetic And Environmental Factors In Gut Disease ✅ > Flashcards

Genetic And Environmental Factors In Gut Disease ✅ Flashcards

1
Q

How many bacteria are there in the gut?

A

> 10^14

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2
Q

Of what phyla do 90% of the normal gut bacteria belong to?

A
  • Gram -ve bacteria

- Gram +ve bacteria

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3
Q

What are gram -ve bacteria also known as?

A

Bacteriodes

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4
Q

What are gram +ve bacteria also known as?

A

Firmicutes

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5
Q

What phyla are the remaining 10% of normal gut bacteria made up of?

A
  • Proteobacteria

- Actinobacteria

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6
Q

Give 2 examples of proteobacteria?

A
  • E coli

- H pylori

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7
Q

What are the normal bacteria in the gut important for?

A

Regulation of innate and adaptive immune system

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8
Q

What bacterium is important in the regulation of the innate immune system?

A

Bacteriodes thetaiotaomicron

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9
Q

What does Bacteriodes thetaiotaomicron regulate?

A

Antimicrobial peptide, e.g. angiogenin, in the intestinal epithelium

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10
Q

How does Bacteriodes thetaiotaomicron regulate antimicrobial peptides?

A

Through direct activation of Toll-like receptors (TLR) on Paneth cells

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11
Q

Where are Paneth cells found?

A

In the crypts of Lieberkuhn

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12
Q

What do Paneth cells secrete?

A
  • Defensins
  • Lysozyme
  • Phospholipid A2
  • Anti-tumour necrosis factor
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13
Q

What is the importance of the substances secreted by Paneth cells?

A

They are all involved in intestinal antimicrobial activity

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14
Q

What are the adaptive immune functions of the gut determined by?

A

Specific bacteria

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15
Q

What cells are involved in the adaptive immune response of the gut?

A
  • Intraepithelial lymphocytes
  • T regulatory cells
  • Th17 cells
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16
Q

How is genetic susceptibility in inflammatory bowel disease demonstrated?

A

Higher rates in other family members of patients

17
Q

What evidence is there to suggest that the environment plays a significant role in inflammatory bowel disease?

A
  • Incomplete concordance between monozygotic twins

- Higher incidence in immigrants who move to high prevalence countries

18
Q

What is the concordance rate of inflammatory bowel disease in monozygotic twins?

A

44-58%

19
Q

What has been identified as a susceptibility gene for inflammatory bowel disease?

A

NOD2/CARD15 gene

20
Q

What has the NOD2/CARD15 gene been shown to have a central role in?

A

The regulation of the innate immune system

21
Q

What has a genome-wide association study identified regarding the NOD2/CARD15 gene?

A

Over 160 loci, with 110 of these loci shared between UC and Crohn’s disease

22
Q

What significant overlap has been demonstrated regarding the loci of the NOD2/CARD15 gene?

A

Other diseases, including psoriasis, T1DM, ankylosing spondylitis, and primary immune deficiencies

23
Q

What has been found regarding the intestinal microbiome in patients with inflammatory bowel disease?

A

There are alterations in the intestinal microbiome in patients with inflammatory bowel disease, both at diagnosis and subsequently

24
Q

What treatment is based on the idea that the intestinal microbiome is altered in patients with inflammatory bowel disease?

A

Faecal transplants

25
Q

Have faecal transplants be proven to work in inflammatory bowel disease?

A

Preliminary studies have shown a reduction in symptoms in some individuals

26
Q

How does coeliac disease typically present?

A
  • GI symptoms
  • Poor growth
  • Malnutrition
27
Q

How are an increasing number of children being diagnosed with coeliac disease?

A
  • Following presentation without GI symptoms

- Following screening in high risk groups

28
Q

When can coeliac disease develop?

A

Any time during childhood or adulthood

29
Q

What does the term ‘coeliac iceberg’ mean?

A

There are many undiagnosed, relatively asymptomatic people with coeliac disease

30
Q

What genes are involved in coeliac disease?

A
  • HLA-DQ2

- HLA-DQ8

31
Q

What % of patients with coeliac disease have HLA-DQ2 or DQ8?

A

95%

32
Q

What is the negative predictive value of testing for HLA-DQ2 or DQ8 in suspected coeliac disease?

A

Close to 100%

33
Q

What % of the population are HLA-DQ2 or DQ8 positive?

A

40%

34
Q

Who is at an increased risk of coeliac disease?

A
  • Those with first degree family members affected

- Patients with T1DM, autoimmune liver disease, Down’s or Turner’s syndrome

35
Q

What evidence is there for environmental factors being involved in the development of coeliac disease?

A

Absence of complete concordance in monozygotic twins

36
Q

What is the concordance rate for coeliac disease in monozygotic twins?

A

70-85%

37
Q

What environmental factors are associated with coeliac disease?

A
  • Low birth weight
  • Neonatal infection
  • Artificial feeding in infancy
  • High socio-economic status

TAS Gastroenterology (17 decks)

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