Microbial Symbiosis with Humans

Question 1

what is dysbiosis?

Answer 1

It is a disruption of the microbiome resulting in an imbalance in microbiota

Question 2

What do we know about diversity and dynamics of microbial populations in humans

Answer 2

• body caries about equal numbers of human cells as bacterial cells
  -species r very diverse across individuals but phyla are pretty similar
  Mostly firmicutes followed by bacteriodetes
  Bacteriodetes rule stool
  Firmicutes supreme in vagina

Question 3

Skin Microbiota

Answer 3

• difficult to colonize(salty, acidic, protective oils, dry)
• composition influenced by environmental factors, host factors (hygiene, puberty), each microenvironment like dry skin, moist skin and sebaceous skin
• mostly Gram +ve bacteria because they’re more resistant to salt and dryness

Question 4

S. epidermis

Answer 4

• skin commensal interactions with S.aureus
  produces Abx that prohibits colonization and biofilm formation by S.aureus by producing endopeptidase, induces keratinocytes to produce antimicrobial peptides to kill S. aureus

Question 5

S.hominis

Answer 5

-skin commensal interactions
produces antibiotics synergies with human antimicrobial peptide to decrease S.aureus colonization

Question 6

Propionibacterium acnes

Answer 6

• causes acne, degrades skin oil, inflames sebaceous glands and causes acne
• skin commensal interactions

Question 7

Oral Cavities and Airways Microbiota

Answer 7

• complex heterogenous microbial habitat
• saliva contains antimicrobial enzymes
• high [nutrients] promote local growth
  normally harms but can enter bloodstream producing bacteremia

Question 8

Bacteremia

Answer 8

bacteria in blood, big uh oh cause bacteria should be sterile

Question 9

Prebiotics

Answer 9

carbohydrates that are indigestible by human host but feed fermentative gut bacteria, promotes growth of “good” bacteria

Question 10

Probiotics

Answer 10

living microbes ingested to restore natural microbial balance, confer health benefit to the host
don’t know they work or if they really do
- commonly used genera: bifidobacterium, lactobacillus
- food supplements not medicine
- contraindicated for immunosuppressed patients

Question 11

Recommended clinical uses probiotics

Answer 11

• reduces the risk of Anxiety associated diarrhea
  -increases remission rates in adults with ulcerative colitis
  -reduces the incidence of necrotizing enterocolitis

Question 12

Bifidobacterium and Lactobacillus

Answer 12

• commonly found in yogurt and probiotic
• easily destroyed
• by acid pH of stomach
  -enzymes and bile acids
• obligate anaerobe: lil bitches when oxygen is around

Question 13

Probiotic Theory

Answer 13

• they may work by taking up space, limiting the ability of pathogens to colonize the gut, they don’t colonize though they work temporarily

Question 14

Oral and Nasal Cavities

Answer 14

• Have normal microbiota, infants mouth colonized with gram -ve(neisseria) and gram +ve(S, lactobacillus actinomyces),
• as teeth emerge other bacteria start growing, prevotella–> gums and teeth s.mutans –> enamel

Question 15

Lower Respiratory Tract

Answer 15

• first thought to be sterile but does harbour limited normal microbiota,
• ciliated mucus lining -> mucociliary escalator: sweeps foreign particles up and out of lung
  lungs are really delicate so it can’t use strong immune responses, it kinda takes care of it’s self through mucus secretion and surfactants by epithelial cells

Question 16

upper respiratory tract

Answer 16

• microbes thrive, wet warm air
  enter through breathing but are trapped in mucus and are expelled sneezing or swallowed then killed in stomach

Question 17

kidney and bladder microbiota

Answer 17

not a thing they are sterile but if environment changes big deal E.coli and P.mirabilis cause UTIs in biological women (super common infection, top 10 reasons ppl see doctors)

Question 18

STIs (sexually transmitted disease)

Answer 18

sometimes include UTIs (even though really UTIs are bladder infections)
important cause of patient morbidity

Question 19

Female genital tract microbiota

Answer 19

• weakly acidic with tons of glycogen
• tons of lactobacillus acidophilus which ferment glycogen and produce lactic acid
• lactic acid keeps it acidic
  -L.acidophilus colonizes at puberty, when not of fertile/child bearing age pH is neutral
• Yeast is opportunistic commensal it’s usually their handy dandy but when L. acidphilus is displaced cause the environment changed or smt Abx, douching, semen

Question 20

Male genital tract microbiota

Answer 20

• understudied
  circumsion is the biggest influence on the composition of penis microbiome
  foreskin covers glands allowing for anaerobic bacteria growth
  also affected by sex and age
  no known commensals yet
  shared microbiota bwt sexual partners

Question 21

Traits of human GI tract and Microbiota

Answer 21

• mono gastric, omnivorous
• microbes in gut affect early development, health and predisposition to disease
• colonization of gut begins at birth
  3 different environments storage small I and large I
  response
• responsible for digestion of food, absorption of nutrients and production of nutrients

Question 22

Trends down the GI system

Answer 22

• less and less oxygen
  -pH increases and so does the # of cells
  1-4h to transit from stomach to the large intestine
  24h from mouth to anus

Question 23

GI microbiota diversity

Answer 23

3 major bacterial phyla: firmicutes, bacteroidetes, and proteobacteria
limited phyla diversity but high high species diversity

Question 24

Stomach and Small Intestine

Answer 24

acidity (pH abt 2) makes it hard to colonize
decreased acidity + hypochlorydia because cholera survives stomach passage and can establishes infection

Question 25

Helicobacter pylori

Answer 25

can survive at pH 1 burrows into gastric mucosa can cause gastric ulcers, has been found in 50% of the world’s population

Question 26

Large Intestine

Answer 26

anoxic
1000 anaerobes:1 facultative organism
micro-organism carry metabolic runs that produce metabolites we need: vitamin production, mod of steroids, aa biosynthesis
tons of fermentation

Question 27

Role of commensal bacteria in our gut

Answer 27

• development of innate and adpative immunity
• microbial barrier
• maintain epithelial integrity
• source of energy
• vitamin biosynthesis, transformation of bile salts, catabolism of complex plant sugars and mucins,
• metabolism of xenobiotics

Question 28

How is an immune response to a gut infection triggered

Answer 28

1. there must be stimulation of innate cells: if barriers are broken, there’s an imbalance or deregulation
2. the severity of pathology is a consequence of the host/pathogen relationship: for example the virulence of the microbiome influences response

Question 29

Clostidium Difficile

Answer 29

commensal bacteria that causes an opportunistic infection
on the rise,
when Abx disrupt balance and kill commensal bacteria c. diff can over colonize and produce toxins
symptoms: diarrhea, fever, loss of appetite nausea, abdominal pain

Question 30

When do humans gain their adult gut microbiota composition?

Answer 30

Adult-like gut microbiota comp is reached at 3 years of age, adult microbiome begins to develop before birth sourced from placenta, once out of embryonic membrane exposed to a lot more microbes from birth canal and outside
baby microbiomes more divers than that of adults

Question 31

How does microbiome change with age and time

Answer 31

adult microbiota relatively stable 70% match over 5 years
bacteriodetes stay relatively stable
early experiences determine gut microbiomes
aging associated with decrease diversity (at home more diverse than in a home)

Question 32

What is the hygiene hypothesis

Answer 32

our use of soaps, antibiotics and disinfectants has restricted our access to microbes so our microbiota appears less diverse, the narrowing of diversity could potentially contribute to inflammatory and auto immune disease

Question 33

How does diet affect microbiota

Answer 33

breast-fed vs bottle -fed: breast fed babies have more commensal bacteria because breast milk has complex oligosaccharides that promote their colonization
at 4 months Brest-fed have more of taxa associated with probiotics, gut lining protection and immune system education (B. longum) bottle-fed have greater abundance of D.diff, citrobacter and enterobacter

High-fiber: can only be fermented by microbiota enzymes and causes the pH of colon to lower which selects bacteria that are able to survive acidic environment

High meat: lots of animal proteins can lead to production of harmful bacteria metabolites

Question 34

Inflammatory diseases: Crohn’s and uc

Answer 34

result of dysbiosis which can be due to abx or failure to develop tolerance
seems to have lower gut microbiome diversity
IBD may be transmissible through genome

Question 35

How have mouse models helped with understand obesity

Answer 35

• it seems that mice that are genetically obese have more firmicutes and methanogens than lean mice
• normal mice are fatter than germ free mice after fecal transplant germ-free start gaining weight
• obese twin lean twin study: recipient mice with same diet which receive transplant from obese humans become obese

Question 36

How are obesity and dysbiosis linked?

Answer 36

Microbes digest food we can’t and produce SCFAs that our cells use, the amounts and rations of these SCFAs can influence obesity, so if there’s dysbiosis and these ratios are modified it can lead to obesity

archaea tilt metabolic balance towards obesity so dysbiosis favouring them can lead to obesity

if gut microbes cause inflammation in situations of dysbioysis
- lipopolysaccharides or endotoxins produced by gram negative species can promote inflammations
- high fat diets can the promote the absorption of theses toxins across the intestinal epithelium