106 - Gut Microbiota Flashcards
Proportion of faeces that is bacteria
~30%
Type of organism that makes up the majority of GIT microbiome
Anaerobic bacteria
Main phyla of GIT bacteria
Bacteroidetes, Firmicutes, Actinobacteria, Proteobactiera (relatively rare, EG: E coli)
Similarity of microbiota between twins
Under 50% bacterial species shared
Processes that genes from microbiota are important for 1 2 3 4
1) Metabolism
2) Development
3) Immune system
4) Protection against enteropathogens
How can the microbiome aid in development?
Intestinal epithelial cell maturation, angiogenesis, lymphocyte development
Factors influencing GIT microbiota 1 2 3 4 5
1) Mode of birth
2) Age
3) Diet
4) Antibiotics
5) Genetics and environment
6) Chronic inflammation
How can mode of birth affect microbiome?
Vaginal delivery associated with rapid acquisition of Firmicutes, Bifidobacteria.
C-section associated with delayed microbiome development, reduced diversity
How can age affect GIT microbiome?
Diversity increases with age
How can diet affect GIT microbiome?
Breast milk, low fat/fibre-rich, high fat/high sugar all can affect microbiome
Effect of animal-based diets on microbiome
Increases levels of bile-tolerant bacteria (Bacteroides), decreases levels of bacteria that metabolise dietary plant polysaccharides
Two theories explaining why germ-free mice need higher calorie diet to maintain body weight
1
2 i, ii
- The microbiota directly supply nutrients from dietary
substances, (eg vitamin B2, vitamin K, biotin, folate,
CHO from plant sugars – 10% calories) - The microbiota alter metabolic machinery of host cells by:
i) inducing changes in host genes involved in CHO and
lipid metabolism, and
ii) maintaining enterocyte
differentiation and function (short chain fatty acids,
SCFA’s)
How do GIT microbiota have a similar effect between individuals, even if the species distribution varies?
Metabolic pathways remain stable between individuals in a healthy population (calculated by examining 16s rRNA ofgut microbiota)
Gut microbiota metabolism of carbohydrates
Lactose, cellulose, mucins broken down into SCFA
How can gut microbiota lead to synthesis of mucus?
Bacterial degradation of host glycans (mucin, chondroitin, sulphate, etc) elicits synthesis of new glycans by host
How can gut microbiota promote gut wall integrity?
Produce short chain fatty acids from undigestible
carbohydrates (eg butyrate) that maintain enterocyte
differentiation
How can bacteria contribute to adiposity?
1
2
1) Complex carbs metabolised to SCFA (acetate, propionate, butyrate)
2) SCFA inhibit histone deacetylase, and metabolic regulation through binding to GPCR.
Where are Peyer’s patches located?
Small intestine
Where in vili do lymphocytes often sit?
Lamina propria, intraepithelial lymphocytes
Intraepithelial lymphocytes
Gamma/delta T lymphocytes, sit in the gut epithelium
Cells within the GIT that release IL-22
NK cells (NK-22)
Role of IL-22 in the gut
Increase antimicrobial defence, epithelial repair, barrier integrity
Cell subtype that invariant lymphoid cells resemble
Th17
What do mucosal associated invariant T cells detect?
Not completely understood.
Respond to bacterial antigens (EG: riboflavin) presented on an MHC-I-like molecule (are mostly CD8+)
NKT cell receptor
CD1d, presenting lipid antigen
Ways in which DCs in the GIT can sample antigen
1) Directly from gut lumen
2) Indirectly, delivered by goblet cells or M cells
Functions of gut DCs 1 2 3 4
1) In steady state, induce Treg (TGFb), Th2 (anti-inflammatory environment)
2) In inflammatory conditions, induce Th1, Th17
3) Bias B cell isotype switching to IgA
4) Induce mucosal addressin alpha4beta7 on activated T and B cells and receptors for mucosal chemokines
alpha4beta7 ligand
MAdCAM1 (only expressed on HEV, epithelial cells of mucosal tissues)
