Genetic And Environmental Factors In Gut Disease ✅ Flashcards
How many bacteria are there in the gut?
> 10^14
Of what phyla do 90% of the normal gut bacteria belong to?
- Gram -ve bacteria
- Gram +ve bacteria
What are gram -ve bacteria also known as?
Bacteriodes
What are gram +ve bacteria also known as?
Firmicutes
What phyla are the remaining 10% of normal gut bacteria made up of?
- Proteobacteria
- Actinobacteria
Give 2 examples of proteobacteria?
- E coli
- H pylori
What are the normal bacteria in the gut important for?
Regulation of innate and adaptive immune system
What bacterium is important in the regulation of the innate immune system?
Bacteriodes thetaiotaomicron
What does Bacteriodes thetaiotaomicron regulate?
Antimicrobial peptide, e.g. angiogenin, in the intestinal epithelium
How does Bacteriodes thetaiotaomicron regulate antimicrobial peptides?
Through direct activation of Toll-like receptors (TLR) on Paneth cells
Where are Paneth cells found?
In the crypts of Lieberkuhn
What do Paneth cells secrete?
- Defensins
- Lysozyme
- Phospholipid A2
- Anti-tumour necrosis factor
What is the importance of the substances secreted by Paneth cells?
They are all involved in intestinal antimicrobial activity
What are the adaptive immune functions of the gut determined by?
Specific bacteria
What cells are involved in the adaptive immune response of the gut?
- Intraepithelial lymphocytes
- T regulatory cells
- Th17 cells
How is genetic susceptibility in inflammatory bowel disease demonstrated?
Higher rates in other family members of patients
What evidence is there to suggest that the environment plays a significant role in inflammatory bowel disease?
- Incomplete concordance between monozygotic twins
- Higher incidence in immigrants who move to high prevalence countries
What is the concordance rate of inflammatory bowel disease in monozygotic twins?
44-58%
What has been identified as a susceptibility gene for inflammatory bowel disease?
NOD2/CARD15 gene
What has the NOD2/CARD15 gene been shown to have a central role in?
The regulation of the innate immune system
What has a genome-wide association study identified regarding the NOD2/CARD15 gene?
Over 160 loci, with 110 of these loci shared between UC and Crohn’s disease
What significant overlap has been demonstrated regarding the loci of the NOD2/CARD15 gene?
Other diseases, including psoriasis, T1DM, ankylosing spondylitis, and primary immune deficiencies
What has been found regarding the intestinal microbiome in patients with inflammatory bowel disease?
There are alterations in the intestinal microbiome in patients with inflammatory bowel disease, both at diagnosis and subsequently
What treatment is based on the idea that the intestinal microbiome is altered in patients with inflammatory bowel disease?
Faecal transplants
