Microbiota - Fan 2/25/16 Flashcards Preview

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Flashcards in Microbiota - Fan 2/25/16 Deck (19)
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1
Q

new view of microbiome as an…

  • ________
  • composition
  • interchangeable terms
A

microflora = microbiota = microbiome

idea of microbiome as an organ, that starts to develop during birth, undergoes growth/maturation

  • 1014 organisms
    • 1% euks, archaeons, viruses
    • 99% bacteria
    • composition can vary based on: age, diet, individ genetics
2
Q

dysbiosis

A

abnormal microbiome that accompanies disease state

3
Q

microflora distribution

A
  • mouth: lots of bacteria
  • stomach: almost all bacteria are killed; near sterile environment - only H. pylori
  • duodenum/jejunum: slight increase in number of bacteria, but not much
  • ileum: at lower end of ileum, by ileo-cecal sphincter, you get a huge jump in bacterial number
  • colon: highest concentration of bacteria - mostly anaerobes, small quantity of aerobes and facultative anaerobes
  • *bacteria account for 2/3 of fecal volume!!!
4
Q

host microbial interactions

A
  • commensalism
  • mutualism: relatively new concept; recent studies challenge it
  • parasitism: recent studies suggest that microbiota as a whole have negative impacts on human health

takehome message: human microbiota is a double-edged sword

5
Q

key research tools for microbiota

A

metagenomics: ID of all microbes using high-throughput DNA seq

gnotobiotic animals: only contain certain known strains [compare physio diffs between different groups of same species]

  • combined with the high throughput sequencing, this is a powerful technique to see whether human/animal microbiota are successful AND which orgs have been successfully transplanted

high sensitivity instrumentation for studying metabolism

6
Q

host-microbiota interactions

A

benefits for microbes

  • food
    • indigestible components of food (ex. dietary fibers)
    • aged gut epithelial cells and secreted proteins
  • stable, protected environment

effects on human hosts

  • benefits: many
  • harms: many
7
Q

role of microbiota in regulating GI tract devpt

(1960s study - mice made germ free using antibiotics)

A

compared to germ free mice, normal mice showed:

  • thickening of muscle layer : improved motility
    • recall pathway: gut bacteria stimulate nerve cells to release a growth factor for macrophages → feeds back onto ENS system, maybe in a way that provides neurocrines to muscle cells
    • also a role for bacteria interacting with bile salts: if you inhibit bacterial-derived bile salt hydroxylases → inhibit gut motility
  • stimulation of GALT (gut assoc lymphatic tissue)
  • stimulating epi cell generation/turnover
  • increasing cellularity of lamina propria
    *
8
Q

gut microbiota nutrition/metab

A

increase nutritional efficiency

  • the gene pool of the microbiome is 150x the size of the human genome - has a lot more digestive enzymes to draw on
  • calorie salvage: supplies short chain FAs from otherwise indigestible foods
    • ex. propionate, butyrate, acetate (produced by bacteria, used by host)
  • supply essential a.a.s
  • supply vitamins (K, B12, biotin, folic acid, pantothenate)
  • aid in colonic conversion of BS to BA
  • alters intrinsic metabolic machinery → more efficient nutrient uptake/util
9
Q

gut microbiota: role in obesity/metabl syndrome

A
  • dysbiosis in DM2 patients
    • drop in butyrate-producing bacteria
    • rise in opportunistic pathogens
    • restoration of microbiota ever after gastric bypass
    • artificial/noncaloric sweetners can favor prodiabetic gut microbes
  • obese-prone mice stay lean after clearing out microbiota, become fat again after reintro
  • thought: metab syndrome is regulated by host gene-microbiota interactions
  • microbial biota are linked to diff DM1 pops in humans
10
Q

gene/gut microbiota interactions: metabolic syndrome

A

TLR5 (Toll-like receptor 5, req for innate immunity) KO mice display:

  • metabolic syndrome (hyperlipidemia, HTN, high insulin resistance, high adiposity)
  • dysbiosis

tx with antibiotics reverses metab syndrome in TLR5-null mice

transplant of TLR5-null microbiota inter germ-free mice = metabolic syndrome

11
Q

gut microbiota: role in malnutrition

A
  • Malawi twins: one healthy, one with kwashiorkor
    • kwashiorkor twin microbiota develop differently
  • “transit maturation” of micriobiota once tx was started (peanut-based, ready-to-use food)
    • regression once Malawi diet was resumed
  • severe weight loss in gnotobiotic mice with the kwashiokor-twin microbiota and not with mice with the healthy-twin microbiota
12
Q

gut microbiota in immunity

A

part of host’s innate immune system

  • traditional idea: microbiota compete with pathogens for nutrients/adhesion sites, suppress pathogen growth
  • produce antimicrobial factors [bacteriotoxins, bile acids, lactic acids, H2O2)
  • toxin degradation
  • general stim of immune fx (phagocytosis, antibody/cytokine production, GALT devpt)
    • no Peyer’s patches in germ-free mice!
    • M cells sample microbes and prsent antigens to lymphocytes

but might also be a pathogen helper!!!

  • might be a role for use of antibiotics as tx for virus - knock out viral pathogen-helping microbiota!
13
Q

consequence of antibiotic use

A

dysbiosis!!!

ex. C. diff infection

14
Q

microbiota-associated conditions

A
  • cancer (colorectal)
  • inflammatory disease (IBD, arthritis)
  • autoimmune disease (experimental demyelinating encephalitis = animal MS)
  • mental health
  • aging
15
Q

mucosal defense: innate and acquired

ANATOMIC FACTORS

(upregulated by microflora)

A
  • mechanical barrier: cont epithelium with tight jx between cells
  • endocytosis/killing of pathogens (esp by epi cells, M cells)
  • complement (pl protein that can lyse bacterial pathogens)
  • granular leukocytes (neutrophils, macrophages, eosinophils)
  • GALT
  • other immune cells: NK cells
16
Q

mucosal defense: innate and acquired

microbiota

A
  • competition with pathogens
  • production of antimicrobial factors
  • toxin degradation
  • gen stim of immune fx (GALT devpt, antibody/cytokine production, endocytosis)
  • helping hand for some pathogens
17
Q

mucosal defense: innate and acquired

MOTILITY AND SECRETION

A
  • mechanic cleansing
  • NaHCO3, HCl
  • mucin, lysozyme, lactoferrin
  • sIgA (secretory IgA)
    • ​acquired immunity
    • passive: in breastmilk
18
Q

mucosal defense: innate and acquired

A
  1. anatomic factors (upreg by microflora)
  2. microbiota
  3. motility and secretion
19
Q
A