9_Microbiota Flashcards
normal flora:
define
- 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
how much of the normal flora is:
- anaerobic
- facultative
- > 90% are anaerobic Gram negative bacteria
- 107 are facultative Gram negative bacteria; mostly bacilli
The rest of microbes are mix of Gram positive cocci, fungi, and viruses
beneficial effects of the normal flora of the GI tract
- 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
what are the normal flora of the GI tract?
(categories and specific bacteria)
-
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
microbiome vs. microbiota:
define
-
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
what are some diseases states of the microbiome?
- ulcerative colitis (UC)
- Crohn’s disease (CD)
- inflammatory bowel disease (IBD)
How does the core gut microbiome in obese and lean twins compare?
(a study)
- 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
probiotics:
define and examples
- 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
- VSL#3, a mix of 8 bacteria, incl. L.
fecal transplant:
define,
- 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
Kellogg’s findings and what effect did this have?
- 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
Colonic cleansing:
define
- 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
pathogenic effects of the normal flora in the GI tract?
-
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
CC: sepsis
life threatening organ dysfunction caused by a dysregulated host response to infection;
identified by change in SOFA score (sequential sepsis related organ failure assessment)
CC: septic shock
subset of sepsis where the underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality
How do infections and sepsis overlap?
- **bacteremia
- fungemia
- parasitemia
- viremia
what are the non-septic causes of SIRS?
(systemic inflammatory response syndrome - SIRS)
- trauma
- burns
- injury
- ischemia
how do the gram positive cell walls and the gram negative cell walls differ?
- Gram negative cells have the gram negative outer envelope;
- the outer membrane contains LPS (lipopolysaccharide)
what causes the endotoxic activity in gram negative bacteria?
- LPS (lipopolysaccharide) contains the endotoxic activity of Gram negative bacteria
- the TOXIC activity is in the lipid portion of the molecule
What are the symptoms caused by endotoxins from different organisms?
they all lead to the same constellation of symptoms:
- fever, chills
- disseminated intravascular coagulation
- BP to fall (hypotonic shock)
- multiorgan failure
- death
O antigens:
define
- 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)
core antigens:
define
- repeating units of 3-6 polysaccharides that are somewhat conserved w/in a genus
- part of LPS (endotoxin)
lipid A:
define
- multiple long chain fatty acids attached to a backbone of glucosamines; conserved w/in a genus
- part of LPS (endotoxin)
what do you call the endotoxins of genera that are missing O antigens?
LOS: lipooligosaccharides
Ex. Neisseria
How do Endotoxins and Exotoxins differ?
how do almost all gram negative organisms have endotoxic activity, even with diff’t structures?
- 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)
which pattern recognition receptor recognizes LPS?
LPS is recognized by the Toll-like receptors?
TLR – Ligand – Target microbes
- TLR 1
- TLR 2
- TLR 3
- TLR 4
- TLR 5
- TLR 1 – triacyl lipopeptides – mycobacteria
- TLR 2 – peptidoglycans, GPI-linked proteins, lipoproteins, zymosan – gram-positive bacteria/trypansosomes/mycobacteria/yeasts and other fungi
- TLR 3 – lipoteichoic acid (dsRNA) – viruses
- TLR 4 – LPS, F-protein – gram-negative bacteria, respiratory syncytial virus (RSV)
- TLR 5 – flagellin – bacteria
what is the pathophysiology of Septic shock and Multiple organ failure?
- 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
cytokine and it’s respective functions:
- IL-1
- IL-12
- TNF-alpha
- IL-6
- IL-8
- 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)
describe the ligand and effector of TLR-4
TLR 4 responds to LPS, F-protein
Targets gram-negative bacteria and respiratory syncytial virus (RSV)
podiatry and septic shock?
when will you see it?
- 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
