16. introduction to the Gut Microbiota Flashcards
when is our GUT MICROBIOTA ESTABLISHED
in first few years of life
(but fragile)
(especially first 10 days)
our MICROBIOTA CO-EVOLVE with…
the IMMUNE SYSTEM
MICROBIOTA GENE SET is how many times the HUMAN GENOME
150X
MICROBIOTA are IMPACTED by
*DIET
- ENVIRONMENT
- HOST GENOTYPE
- AGE (fragile again later in life)
- DISEASE
- type of birth, type of feed (breastfeed)
- Inflammation
how is a FETUSES FIRST FAECES - MECONIUM
STERILE
no microbiomes
on DAY 2 of life which BACTERIA could be isolated
- COLIFORM BACTERIA eg E. COLI (first colonisers)
- LACTOBACILLI (in breast milk and vagina)
- ENTEROCOCCI
STRAINS of which BACTERIA can be found on DAY 3
BACTEROIDES
which BACTERIA be found on 5TH DAY
BIFIDOBACTERIA
GUT MICROBIOTA SHAPES INTESTINAL…
IMMUNE SYSTEM
how is GUT MICROBIOTA is HEALTHY INDIVIDUALS
- HIGHER TAXONOMIC DIVERSITY (number and relative abundance of species in a community)
- HIGHER GENE DIVERSITY
- Microbial communities are important for DEVELOPMENT and STABILITY of IMMUNITY
- HOST-MICROBIOTA MUTUALISM
- Bacteria CONTROLLED BY the INTESTINAL BARRIER (mucus) and underlying MUCOSAL IMMUNE COMPARTMENT
what is meant by HOST-MICROBIOTA MUTUALISM
2 ORGANISMS of DIFFERENT SPECIED CO-EXIST
& each individual BENEFITS from the ACTIVITY OF THE OTHER
- relationship where both benefit from each other
what are BACTERIA in our GUT MICROBIOTA CONTROLLED BY
INTESTINAL BARRIER and UNDERLYING MUCOSAL IMMUNE COMPARTMENT
name the 6 MAJOR PHYLA (level of classification or taxonomic rank)
90%:
- FIRMICUTES
- BACTEROIDETES
lower numbers:
- ACTINOBACTERIA
- PROTEOBACTERIA (can become pathogenic)
- FUSOBACTERIA
- VERRUCOMICROBIA
what are the DOMINATING BACTERIA in the DISTAL GUT especially Ascending and Transverse COLON
FIRMICUTES and BACTEROIDETES
how is the MUCUS LAYER in the COLON
2 LAYERS
Inner: free from bacteria
Outer: legislator of HOST-MICROBIAL INTERACTIONS (bacteria present)
& CONTINUOUS
2 MUCUS LAYERS in the COLON are ORGANISED by which MUCIN GLYCOPROTEIN
MUC2 MUCIN
which COLON MUCUS LAYER has BACTERIA
OUTER LAYER
WHERE is MUCUS CONTINUOUS / DISCONTINUOUS
stomach?
small intestine?
colon?
CONTINUOUS in STOMACH & COLON
DISCONTINUOUS in SMALL INTESTINE (for efficienct absorption)
why are HIGH FRUIT, LEGUME and FIBRE DIETS beneficial for GUT HEALTH
more GRAM+ bacteria
more saccharolytic species (anaerobic)
(& less pathogenic intestinal bacteria)
HIGH SCFA LEVELS (short-chain fatty acids)
SCFAs are a subset of FATTY ACIDS with how many CARBON MOLECULES
6 OR LESS
SCFAs in bowel
ACETATE
PROPIONATE
BUTYRATE (main source of energy)
SCFAs from bowel are taken up into circulation and then FURTHER METABOLISED by…
LIVER
what can you get from ANUMAL BASED DIET
HARMFUL BRANCHES ISO- SCFAs
where are SCFAs ABSORBED
LARGE INTESTINE
SCFA UPTAKE by which TRANSPORTER/RECEPTOR
MCT (monocarboxylate) TRANSPORTER/RECEPTOR
how can SCFA be ABSORBED
- MCT TRANSPORT/RECEPTOR - transcellular
or - DIFFUSION through APICAL MEMBRANE
and TIGHT JUNCTIONS
MAJOR SOURCE of ENERGY for the BOWEL
BUTYRATE
BUTYRATE (BT)also acts as
POTENT INHIBITOR of HISTONE DEACETYLASES (HDAC)
ENHANCES TUMOUR SUPPRESSOR GENE EXPRESSION
- ANTI-CANCER agent
SCFA RECEPTORS are what type of receptors
G-PROTEIN COUPLED
SCFA RECEPTORS REGULATE..
METABOLIC ACTIVITY of gut MICROBIOTA and act as sensors for ENERY EXPENDITURE / CONTROL energy
- link metabolic activity of gut microbiota with host body energy homeostasis
also SENSE NUTRIENTS - SCFA LEVELS
SCFA RECEPTORS can also MODULATE…
IMMUNE SYSTEM
- IMMUNOMODULATORY
SCFA entering PORTAL VEIN under-go …. by the LIVER
FIRST-PASS METABOLISM
within LIVER, SCFA may enter a number of METABOLIC PATHWAYS depending on their metabolic state ie:
- ACETATE and BUTYRATE may be CONVERTED into ACETYL-CoA and used to FORM:
LIPIDS and KETONE BODIES - CITRIC ACID CYCLE used to produce:
GLUCOSE by GLUCONEOGENESIS - ACETATE may pass into PERIPHERAL CIRCULATION and can be DETECTED in PERIPHERAL BLOOD
what can ACETATE and BUTYRATE be used to FORM in the LIVER
LIPIDS and KETONE BODIES (by conversion into Acetyl Co-A)
or (as well as propionate)
GLUCOSE in citric acid cycle (gluconeogenesis)
how does HIGH FERMENTABLE DIET (FRUIT,LEGUME,VEGETABLE, FIBRE) affect BACTERAL DIVERSITY
HIGH BACTERIAL DIVERSITY
(more SCFA production)
low diversity in high fat, sugar, animal protein diet (and more amino acid metabolism and more iso SCFAs)
DYSBIOSIS (imbalance) is the ALTERATION in MICROBIOME caused by CHANGES IN..
- MICROBIOTA COMPOSITION
- MICROBIAL METABOLIC ACTIVITY
- SHIFT in LOCAL DISTRIBUTION of COMMUNITIES of MICROBES
when can MICROBIAL BALANCE be tipped towards PATHOGENIC STRAINS (PATHOBIONTS)
(lose homeostasis)
REDUCED DIVERSITY
LOSS of BENEFICIAL MICROBES (SYMBIONTS)
PATHOBIONT EXPANSION
examples of FACTORA that SHAPE INTESTINAL MICROBIAL COMPOSITION
- CHRONIC INFLAMMATION (IBS,IBD, colorectal cancer, liver disease)
- METABOLIC DYSFUNCTION (ie diabetes, obesity)
- IMMUNODEFICIENCY
- HYPERIMMUNITY
- ANTIBIOTICS
- LIFESTYLE (extreme exercise)
- DIET
- HYGIENE