Lecture 6- Human Microbiome III

Question 1

Immune system basics

Answer 1

Two types;
*innate= non-specific
*adaptive= specific

Question 2

Innate immune system

Answer 2

*physical barriers; skin, organ and mucosal layers
*chemical barriers; stomach acid, lysozyme in the eye
*innate response; inflammatory response cells; mast cells, neutrophils, macrophages + NK cells
- no memory
- fast response
- cells are non-specific

Question 3

Adaptive system

Answer 3

• slower
• macrophage engulfs bacteria + presents its antigen to helper T + cytotoxic T cells
  *CT cells= kill organisms
  *helper T cells recruit B cells= replicate and generate antibodies
  *those tagged with antibodies= set for destruction
• antibodies = immunoglobulins
• cytokines can be released which impact on host cells

Question 4

Immune system interactions

Answer 4

-evolved with resident skin microbes
-skin microbiota, epithelial cells + innate and adaptive arms of the immune system communicate
*keratinocytes = communicate by sensing microorganisms; pattern recognition receptors-identify pathogen-associated molecular patterns

Question 5

Immune system interactions

Answer 5

-binding of PAMPs to PRRs triggers innate immune responses
*secretion of antimicrobial peptides
*kill fungi, bacteria + parasites
-some antimicrobial peptides= controlled by members of the skin microbiota

Question 6

Skin

Answer 6

-focuses on staphylococcus aureus
Antibiotics produced by staphylococcus sp = prevent aureus colonization
*S epidermidis= inhibits S aureus biofilm formation
*production of the serine protease glutamyl endopeptidase (ESP)
- induce antimicrobial peptide production by skin cell = kill S.aureus

Question 7

Skin pathogens

Answer 7

*S.hominis= produces lantibiotics- combine with human antimicrobial peptides to decrease S.aureus colonisation

*Propionbacterium acnes= enhance S.aureus biofilm formation through production of coproporphyrin III

Question 8

Heart disease

Answer 8

*CAD= chronic inflammatory disorder- narrowing of the coronary artery due to plaque formation
^= blocking/reducing oxygen rich blood supply to the heart- may lead to heart attack
*microbiome analysis = presence of oral bacteria in atherosclerotic plaque samples

Question 9

Role of oral microbes

Answer 9

-secrete proteins, peptides and proteases
-altering the host actin cytoskeleton in the gingival epithelium = causes inflammation
-allows bacteria to enter the bloodstream
-numerous types of oral bacteria form biofilms within atherosclerotic plaques = causes CAD

Question 10

Immune response

Answer 10

-secreted proteins activate the immune system = causing inflammation
-cytokines-mediated = associated with CAD
-proteases = activate the complement system generating an inflammatory response

Question 11

Oral microbiota CAD links

Answer 11

-organisms= secrete proteins, peptides + proteases found in the gingival crevice
^ leads to oral microbial entry to the bloodstream

Question 12

Urinary genital tract

Answer 12

-key area for transmission of a number of diseases
-normal microflora
-female menstrual cycle has an impact

Question 13

Vagina

Answer 13

-vagina colonised soon after birth
-during reproductive life= vaginal epithelium contains glycogen due to the actions of circulating estrogens
*lactic acid bacteria predominates= able to metabolise the glycogen to lactic acid
*lactic acid= inhibit colonisation by none lactic acid bacteria

Question 14

Preterm birth

Answer 14

-delivery before 37 weeks of gestation
^Common cause of neonatal morbidity
-half of PTB linked to changes in vaginal microbiota

Question 15

Preterm vs full term

Answer 15

-changes in the vaginal microbiome associated with PTB
-^due to microorganisms travelling from vagina to uterus
-more likely to have increased abundance of; sneathia amnii, prevotella, lachnospiraceae + saccharibacteria; associated with low levels of vitamin D

Question 16

The GI microbiome + health

Answer 16

-highly diverse environment + normal flora
-microbiota play important roles in health

Question 17

Short chain fatty acids

Answer 17

-products of fermentation of dietary fibre in the GI tract
-do not possess the enzymes necessary to produce SCFAs from fibre
-loss of SCFA- producing bacteria linked to T1D, T2D, liver cirrhosis, IBD + atherosclerosis

Question 18

IBD

Answer 18

-complex chronic conditions
-heterogeneity in treatment response
-microbiome implicated in disease outcomes; multiple factors + faecal transplants attempted

Question 19

IBDMDB (inflammatory bowel disease multi’omics database)

Answer 19

Control individuals without IBD
Profiles of microbial microbiota + wider microbiome; mapping both active and quiescent periods of disease

Question 20

IBD

Answer 20

-nearly all microbiome properties change in either activity/stability during disease
-large scale shifts in microbiota over a few weeks - seen in patients with IBD

Outcomes;
-microbiome reverted to a baseline composition when the disease is not active
-IBD patients had microbiome + immune responses that were less stable than none IBD control group
-shifts in microbiome signalled changes in symptoms; both negative and positive

Question 21

Key indicators

Answer 21

Slide 25

Question 22

Gut/brain protection

Answer 22

*meninges= 3 membranes that protect the brain and spinal cord
-range of immune cells are found in the meninges

*plasma B cells= produce antibodies in response to infections
*meningeal plasma B cells= produce IgA (associated with the gut) also positioned next to important blood vessels
*meningeal IgA= originated in the intestine and migrated to the meninges = removal of these cells allowed infection to spread to the brain from the blood

Question 23

The gut brain axis links to disease

Answer 23

Numerous PRRs activate the inflammasome (inflammation pathways)
-some depressive disorders link to this
*inhibition of capase-1 attenuates inflammation + anxiety like behaviours and modulates the composition of gut microbiota

Question 24

Liver dysfunction

Answer 24

-influences immunity + metabolism of gut + a range of organs
-brain malfunction due to *hepatic encephalopathy + kidney disorders= observed in patients with liver ailments
-impaired brain function= seen in patients with advanced liver diseases
-decreased metabolism of ammonia associated with liver failure also associated with HE
-CVD of the heart + blood vessels = associated with fatty liver + other liver disorders

Question 25

Gut-liver axis

Answer 25

*dysbiosis= increases gut permeability = microbial metabolites reach the liver
-affect hepatic immunity + inflammation
- immune cells activated by these metabolites = reach liver through lymphatic circulation
- liver= influences immunity and metabolism in multiple organs
-released bile acids + other metabolites into biliary tract= can enter the systemic circulation

Question 26

Gut microbiome + liver diseases

Answer 26

*non-alcoholic fatty liver disease + non-alcoholic steatohepatitis = associated with gut dysbiosis
-higher abundance of escherichia coli + bacteroids= in the gut of NAFLD patients
-all bacteria are increased during cirrhosis
-pro + prebiotics = improve liver disease symptoms

Question 27

Type 2 diabetes

Answer 27

-associated with statically changes in fasting plasma glucose
-pro/pre/synbiotic supplementation = improved glucose homeostasis in diabetic patients