Lc4: commensal microbes

Question 1

cellular microbes of the human body

Answer 1

fungi
protists
bacteria
archaea

Question 2

fungi

Answer 2

yeasts (unicellular - division by budding)
molds (multicellular - (a)sexual repdroduction

Question 3

protists

Answer 3

• Phylogenetically diverse, mostly unicellular, lack tissue organization
• Important components of many terrestrial, aquatic, and marine ecosystems, contribute to nutrient cycling
• Many are parasitic in humans and animals
• Include:
  o Algae (photosynthetic, possess cell wall produce main part of planet’s oxygen)
  o Protozoa (many motile by presence of e.g., flagella, cilia, pseudopodia)
  o Slime molds

Question 4

archaea vs bacteria

Answer 4

Nucleus –> A:no B:no
membrane bound organelles –> A:no B:no
chromosome –> single circular DNA
cell wall –> A: no peptidoglycan
DNA machinery –> A:eukaryote like
environment –> A:extreme B:everywhere

Question 5

taxonomy - Dear King Phillip Calls Out For Good Soup

Answer 5

domain
phylum
class
order
family
genus
species

Question 6

host-microbe interactions

Answer 6

• Commensals –> organisms that are normally found on those parts of the body exposed to the external environment
• Symbionts –> organisms that are normally found on those parts of the body exposed to the external environment and have a mutually beneficial relationship with their host
• Opportunistic pathogens –> An organism that can cause an infection in individuals with abnormal host defences.
  o Commensals can be opportunistic pathogens
• Pathogens –> organisms that cause infections in an individual with normal host defences

Question 7

microbiota niches

Answer 7

sterile: blood and organs
colonized: skin, RT, GI and UT

Question 8

skin

Answer 8

• Different niches depending on environmental conditions
  o Oily less diverse than dry skin
• Cutibacterium acnes digests lipids from hair follicles (subaceous glands) to create a low pH which is prevents infections of pathogens
  - other strains produce inflammatory agents that may cause acne
• S. epidermidis
  o Secrete antimicrobial peptides
  o Increase tight junction tightness

Question 9

RT

Answer 9

• Environmental conditions (pH, humidity, oxygen level) determine microbiota composition
• Nasal microbiota resembles skin microbiota
• Many viruses also present in upper RT
• Oropharynx most densely populated
• Lower RT long thought to be sterile

Question 10

GI

Answer 10

• Bacteria:
  o 500-1000 different bacterial species
  o 30-40 species make up 99% of total population
• Archea: only three archeal species discovered so far
• Viruses: 10-100 species, many to infect bacteria (bacteriophages)
• Fungi/yeast: 10-100 species (many of which we eat, e,.g. Baker’s yeast)
• Parasite egg’s: better not!
• Unique composition in each individual!
• Increasing numbers from stomach to colon
• Complexity also increases towards colon (slow transit time)
• Anaerobes outnumber aerobes in distal GI tract
• 100 billion (1013-1014) microbes ~1,5 kg
• Low pH in stomach limits bacterial growth
• Bile acids and pancreatic juice in proximal intestine limit bacterial growth

Question 11

small intestine mucus

Answer 11

• 1 loose and permeable layer
• consists of mainly MUC2 (highly glycosylated mucin)
• glycocalyx: membrane bound mucins
• in crypts the mucus is very dense to protect stem cells

Question 12

colon mucus

Answer 12

• 2 layers –> resembles crypts of small intestine
• deep layer is impermeable to microbes

Question 13

metabolic effect of GI microbiota

Answer 13

bacteria ferment:
- starch, NSP and oligosaccharides into organic acids (SCFA) and alcohols and gases
- proteins/AA into nitrogenous metabolites and gases

archaea can produce methane

Question 14

metabolism of indigestible carbs

Answer 14

amylases can break alfa(1-4) glycosidic bonds

bacteria can use CAZs to break beta bonds

products can be used by other bacteria or us

Question 15

bile metabolism

Answer 15

1. cholesterol –> primary bile acids conjugated with AA - glycine or taurine (liver)
2. gall bladder
3. into duodenum
4. bacteria transform primary into secondary (active)

bacteria also assist in recycling of bile acids

Question 16

prudent diet

Answer 16

1. omega-3, phytochemicals, fiber lead to formation of SCFAs
2. increased mucus secreation
3. increased AMP secretion
4. increased barrier function

Question 17

western diet

Answer 17

1. high sugar, high fat, low fiber
2. enhanced mucus degradation
3. reduced AMPs
4. reduced barrier function
5. inflammation

Question 18

colonization at birth

Answer 18

• First microbes originate from:
  o Maternal vagina and gut in vaginally born infants
  o Environment and skin from hospital staff and parents in C-section born infants
• Early facultative aerobic bacteria (E. coli, streptococci) reduce the environment (consume O2)
• This sets the stage for colonization by strict anaerobic bacteria

Question 19

human milk

Answer 19

• Maternal milk contains >100 different human milk oligosaccharides (HMOs):
• Cannot be digested by our own digestive enzymes
• Bifidobacteria are specialized to ferment HMOs into acetate and lactate
• Acetate and lactate are an energy source for the baby and lower intestinal pH –> Lower pH prevents colonization by (opportunistic) pathogens
• Maternal milk also contains bacteria (incl. bifidobacteria) that can seed the infant gut
• Formula-fed infants have more diverse collection of gut microbes, including opportunistic pathogens

Question 20

immune maturation

Answer 20

• cryptopatches become mature lymphoid follicles
• mesnetric and peyer’s also mature
• large role for microbiota in this proces –> sterile conditions lead to lack of maturation

Question 21

SCFAs as antiinflammatories

Answer 21

1. bind to GPR43 on Tregs
2. release of IL10
3. inhibit effector T cells