9_Microbiota Flashcards

1
Q

normal flora:

define

A
  • symbiotes (bc they live in close association w/ the host)
  • some relationships w/ the host are mutually beneficial and some are commensal (where the organisms benefit, but the host does not)
  • If microbes stay confined to the GI tract, they are harmless and may even be beneficial
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2
Q

how much of the normal flora is:

  1. anaerobic
  2. facultative
A
  1. > 90% are anaerobic Gram negative bacteria
  2. 107 are facultative Gram negative bacteria; mostly bacilli

The rest of microbes are mix of Gram positive cocci, fungi, and viruses

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3
Q

beneficial effects of the normal flora of the GI tract

A
  • primes the immune system
  • induces isohemagglutins by cross-reactions
  • excludes pathogens
    • Abx tx that targets normal flora sensitizes to pathogens
    • Human can be sensitized to C. difficile
  • produces vitamin B and vitamin K
  • metabolizes bile salts for recycling
  • metabolizes bilirubin
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4
Q

what are the normal flora of the GI tract?

(categories and specific bacteria)

A
  • Anaerobes
    • bacteriodes species are most numerous
  • Facultative gram negative bacteria
    • E. coli
    • Klebsiella pneumoniae
    • Enterobacter species
    • Proteus species
    • Pseudomonas aeruginosa
    • Citrobacter species
    • Serratia species
  • Gram positive cocci
    • Enterococcus, Staph aureus
  • yeasts
    • Candida albicans
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5
Q

microbiome vs. microbiota:

define

A
  • microbiome: collective genome of the GI tract;
    • up to 40,000 bacterial species identified by 16S RNA
    • most of which are not culturable
    • about 100X as many microbial genes in the gut as human genomes
  • microbiota: actual cultured microbes
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6
Q

what are some diseases states of the microbiome?

A
  • ulcerative colitis (UC)
  • Crohn’s disease (CD)
  • inflammatory bowel disease (IBD)
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7
Q

How does the core gut microbiome in obese and lean twins compare?

(a study)

A
  • compared monozygotic and dizygotic twin pairs;
  • microbiome is shared among family members; but that each person’s gut microbial community varies
  • obesity was assoc. w/ phylum-level changes in the microbiota, reduced bacterial diversity, and altered representation of bacterial genes and metabolic pathways
  • Mice study: Recipient mice had body mass and metabolic characteristics of the donor of the fecal transplant
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8
Q

probiotics:

define and examples

A
  • Probiotics: are live bacteria and yeasts that are good for you, especially your digestive system
  • In general have not been rigorously tested in trials
  • Examples:
    • VSL#3, a mix of 8 bacteria, incl. L.
      acidophilus, L. casei, L. plantarum. L. bulgaricus,
      Bifidobacterium longum, B. breve, B. infantis and
      Streptococcus thermophilus has shown some efficacy in
      ulcerative colitis patients
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9
Q

fecal transplant:

define,

A
  • fecal transplant: (fecal bacteriotherapy) is the process of restoring the bacteria commonly found in the digestive tract with an infusion of feces (stool) from a donor
  • How did the C. difficile patient differ prior to fecal transplant and after?
    • prior to transplant, patient did not have Bacteroides
    • after transplant, the pt DID have Bacteroides and started having normal bowel movements
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10
Q

Kellogg’s findings and what effect did this have?

A
  • Kellogg attributes “neurasthenia” or nervous exhaustion to eating of meat, which leads to growth of putrefying bacteria in the gut
  • Effect
    • Advocates cereals and grains that have fiber
    • Invests in cold cereals
    • Advocates enemas to speed colonic transit and flush out putrefying toxins in a gut
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11
Q

Colonic cleansing:

define

A
  • popular technique to eliminate “toxins” in the GI tract
  • NO evidence that they’re beneficial
  • Side effects:
    • can cause ion imbalances
    • gut perforation
    • amoebic dysentery, if flush water is contaminated
    • adverse effects
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12
Q

pathogenic effects of the normal flora in the GI tract?

A
  • overgrowth of organisms from the large intestine –> small intestine –> malabsorption syndromes
    • malabsorption of fat, vitamin B12, folic acid, and carbohydrates
  • cancer by production of nitrosamines
  • escape from GI tract leading to pneumonia or UTI
  • escape from gram negative bacteria from the GI tract leading to bacteremia, sepsis, endotoxic shock, and multiple organ failure
    • ruptured appendix, perforation of intestine by wounds or accidents
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13
Q

CC: sepsis

A

life threatening organ dysfunction caused by a dysregulated host response to infection;

identified by change in SOFA score (sequential sepsis related organ failure assessment)

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14
Q

CC: septic shock

A

subset of sepsis where the underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality

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15
Q

How do infections and sepsis overlap?

A
  • **bacteremia
  • fungemia
  • parasitemia
  • viremia
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16
Q

what are the non-septic causes of SIRS?

(systemic inflammatory response syndrome - SIRS)

A
  • trauma
  • burns
  • injury
  • ischemia
17
Q

how do the gram positive cell walls and the gram negative cell walls differ?

A
  • Gram negative cells have the gram negative outer envelope;
    • the outer membrane contains LPS (lipopolysaccharide)
18
Q

what causes the endotoxic activity in gram negative bacteria?

A
  • LPS (lipopolysaccharide) contains the endotoxic activity of Gram negative bacteria
  • the TOXIC activity is in the lipid portion of the molecule
19
Q

What are the symptoms caused by endotoxins from different organisms?

A

they all lead to the same constellation of symptoms:

  • fever, chills
  • disseminated intravascular coagulation
  • BP to fall (hypotonic shock)
  • multiorgan failure
  • death
20
Q

O antigens:

define

A
  • repeating units of 3-5 sugars that give antigenic specificity to the organism
  • highly variable from one species or serotype to another
  • part of LPS (endotoxin)
21
Q

core antigens:

define

A
  • repeating units of 3-6 polysaccharides that are somewhat conserved w/in a genus
  • part of LPS (endotoxin)
22
Q

lipid A:

define

A
  • multiple long chain fatty acids attached to a backbone of glucosamines; conserved w/in a genus
  • part of LPS (endotoxin)
23
Q

what do you call the endotoxins of genera that are missing O antigens?

A

LOS: lipooligosaccharides

Ex. Neisseria

24
Q

How do Endotoxins and Exotoxins differ?

A
25
Q

how do almost all gram negative organisms have endotoxic activity, even with diff’t structures?

A
  • LIPOPOLYSACCHARIDES FROM ALMOST ALL GRAM NEGATIVE ORGANISMS HAVE ENDOTOXIC ACTIVITY. HOW CAN THIS OCCUR IF THEY ALL HAVE SLIGHTLY DIFFERENT STRUCTURES? WHAT IS THE RECEPTOR?
  • They have a new class of receptors called “Pattern recognition receptors” (PRRs)
    • these recognize PAMPs (pathogen-assoc. molecular patterns)
    • One class of PRRs is toll-like receptors (TLRs)
26
Q

which pattern recognition receptor recognizes LPS?

A

LPS is recognized by the Toll-like receptors?

27
Q

TLR – Ligand – Target microbes

  1. TLR 1
  2. TLR 2
  3. TLR 3
  4. TLR 4
  5. TLR 5
A
  1. TLR 1 – triacyl lipopeptides – mycobacteria
  2. TLR 2 – peptidoglycans, GPI-linked proteins, lipoproteins, zymosan – gram-positive bacteria/trypansosomes/mycobacteria/yeasts and other fungi
  3. TLR 3 – lipoteichoic acid (dsRNA) – viruses
  4. TLR 4 – LPS, F-protein – gram-negative bacteria, respiratory syncytial virus (RSV)
  5. TLR 5 – flagellin – bacteria
28
Q

what is the pathophysiology of Septic shock and Multiple organ failure?

A
  • release of massive amounts of TNF-alpha and other proinflammatory cytokines –>
  • leads to septic shock and multiple organ failure
  • induction of nitric oxide leads to fall in blood pressure and circulatory collapse
29
Q

cytokine and it’s respective functions:

  • IL-1
  • IL-12
  • TNF-alpha
  • IL-6
  • IL-8
A
  • IL-1 – fever, activated endothelial cells
  • IL-12 – activates NK cells
  • TNF-alpha – causes tissue damage and mediates septic shock
  • IL-6 – induces acute phase proteins in the liver
  • IL-8 – is chemotactic for PMNs (polymorphonuclear leukocytes)
30
Q

describe the ligand and effector of TLR-4

A

TLR 4 responds to LPS, F-protein

Targets gram-negative bacteria and respiratory syncytial virus (RSV)

31
Q

podiatry and septic shock?

when will you see it?

A
  • bacteria in wounds, bed sores, and infected toe nails
  • esp in elderly in care facilities –> can move into blood stream
  • gram negative organisms in the blood stream
    • can give a similar syndrome of septic shock
    • even though they are not seeding from the GI tract
  • gram positive organisms infect skin
    • can also cause sepsis by triggering TLR2, although peptidoglycan is much less potent than LPS