L7: Microbiome manipulation Flashcards
1
Q
who is alexander Flemming
A
- discovered the Penicillium mould secreted an antibacterial substance
- he then named the substance Penicillin
2
Q
what are antibiotics often used for?
A
- ear infections
- presumed Strep infections
- childbirth
3
Q
antibiotic overuse - ear infections
A
most ear infections are viral and not bacterial
4
Q
antibiotic overuse - childbirth
A
moms take antibiotics before birth to prevent newborn infections
5
Q
why do we overuse antibacterial
A
it is bc we do not have the optimal tests to check to see if infections are bacterial or viral
6
Q
what is the missing microbes hypothesis
A
- use of antibiotics are eradicating ancient bacteria that is needed/beneficial
- risk in IBD in children increases with the number of courses of antibiotics taken
7
Q
what is the hygiene hypothesis
A
- suggests that children who are not exposed to germs in early life may develop poor immune tolerance
- can lead to inadequate immune responses that contribute to the development of asthma and other allergic responses
8
Q
who is Barry Marshall
A
- partnered with microbiologists and isolated the bacteria Helicobacter pylori
- they were the 1st to point out that gastritis and peptic ulcer were caused by bacteria
- afterwards, they primarily became treated with antibiotics
9
Q
gastritis and peptic ulcer - prior to Mashall
A
- thought to be caused by access hydrochloric acid (HCl) and stress
- most common treatment was antacids or surgery
10
Q
what is the problem with Marshall’s discovery
A
- there was no clear correlation between the presence of H. pylori and stomach ulcers/gastritis
- the bacterium inhabits >50% of humans
- Marshall used Koch postulates which can be problematic
11
Q
problem with Marshall’s discovery - what does Koch postulates tell us
A
a set of criteria that establish whether a microorganism is the cause of a disease
12
Q
problem with Marshall’s discovery - what are the Koch postulates
A
- organism can be isolated from every diseased host
- organism can be cultured in the laboratory
- the organism is re-introduced to healthy susceptible animal-model
- the organism can be isolated from the new host
13
Q
problem with Marshall’s discovery - what is problematic about the postulates
A
- most microbes cannot be isolated
- the microbes that can be isolated may be present within a person but the person will not develop the disease
14
Q
how can H. pylori be present without making its host sick?
A
- it contains ureases
- enzymes that break down urea in gastric juice
- helps them resist acidic environments
15
Q
what may result because of H. pylori?
A
- its a major cause of gastric cancer because it is a risk factor for peptic ulcers and stomach cancer
- it is unclear the exact involvement between H. pylori and cancer
16
Q
who is Prof. Martin Blaser
A
- found that H. pylori was the dominant microbe in the stomachs of almost all people in the early 20th century
- but by the turn of the 21st century, fewer than 6% of children were carrying it
17
Q
Prof. Martin Blaser - what did his discovery regarding decline in H. pylori imply
A
- that H. pylori is beneficial since it was present in humans and other mammals for more than 100 thousand years
- that the reason for its decrease may be due to antibiotics
18
Q
Prof. Martin Blaser - what did he identify in H. pylori?
A
- CagA+ strains
- they induce enhanced host responses regarding development of atrophic gastritis, gastric cancer, and peptic ulcer compared with CagA- strains
19
Q
explain the experimentally induced asthma experiment
A
- researchers used methacholine challenge induce asthma
- it is used to test for how responsive the lungs are
- and used as a diagnostic for asthma
20
Q
experimentally induced asthma experiment - what are the 3 groups
A
- mice with no H. pylori
- mice that were given H. pylori as infants
- mice that were given H. pylori as adults
21
Q
experimentally induced asthma experiment - what are results
A
mice that were exposed to H. pylori as infants had the most protective effects against asthma
22
Q
how does H. pylori have protective effects - asthma
A
by inducing anti-inflammatory cytokines and suppressing pro-inflammatory cytokines
23
Q
how does H. pylori have protective effects - protection from infections
A
activates immune responses
24
Q
how does H. pylori have protective effects - hormonal
A
- H. pylori produces Lectin and Ghrelin
- it modifies hormones related to hunger and affects hormonal physiology in the stomach
25
explain the co-adaptation of *H. pylori* and humans
- there are benefits of having *H. pylori*
- but benefits are prevalent in early life and declines with age
26
what are germ-free mice
- a line of mice that are no bacteria and are kept in very specific conditions
- used to conduct functionality testing of microbes
27
germ-free mice - pros
- mice are free of all microorganisms in all tissues
- allows for exclusive colonization with defined microbes
28
germ-free mice - cons
- expensive
- requires specialized equipment and training
- new genotypes must be re-derived
- not all experiments are feasible
- developmental defects may make comparisons problematic
29
germ-free mice: cons - developmental defects
- altered immune system
- increased stress response
- behavior
- nutritional deficiencies
- abnormal gut barrier
30
germ-free mice - obesity experiment
- when normal and germ-free mice are given a high-fat diet
- normal mice turned obese with an altered microbiota composition
- germ-free mice remained the same
31
germ-free mice - obesity and microbiome transfer experiment
- all are germ-free mice
- when the donor had a normal weight, the mice had a normal weight
- when the donor was obese, the mice turned obese
- when the donor was underweight, the mice turned underweight
32
germ-free mice - obesity and gut microbiome transfer experiment
- fecal transfer of a obese, non-germ-free mice to a less obese germ-free mice
- results depend on the diet of the germ-free mice, but the mice will turn obese
33
germ-free mice: obesity experiments - what does this imply
that microbes could be the most important factor in obesity
34
why are people now thinking about rewilding animals with microbes
a single course antibiotics can suppress as much as a third of your microbiota
35
rewilding with microbes - define coprophagoa
- eating fecal matter
- it is widely used in other animals to relieve gastrointestinal disorders
36
rewilding with microbes - define cow cannulation
transplanting gastric content from cow to cow to increase digestion
37
what is *Clostridium difficile*
- can cause diarrhea, colitis, and other intestinal conditions
- it is the leading cause of diarrhea associated with antibiotics
38
*Clostridium difficile* - explain the bacteria
- gram positive, obligate anaerobe
- colonization in hospitals or via healthy care workers
- a diverse microbiome is key against *C. difficile* colonization
39
*Clostridium difficile* - why is a diverse microbiome needed to fight it
- a person with a healthy and diverse microbiome may have the bacteria and not experience symptoms
- this is bc the microbiome is suppressing the bacteria's response
40
*Clostridium difficile* - what will happen after antibiotic overconsumption
- over consumption allows *C. difficile* spores to germinate and promote colonization on the gut membrane
- toxins then cause a disruption of the epithelial barrier
- leads to inflammatory response to be activated and release cytokines
- neutrophils then crease a endomembrane
41
what's the most common way to treat *Clostridium difficile*
antibiotics and antacids
42
*Clostridium difficile* - alternate methods of treatment
- fecal microbiome transplant (FMT)
- bacterial monotherapy
- artificial microbial communities
- bacteriophages
43
*Clostridium difficile* - fecal microbiome transplant
involves transferring stools from healthy donors into the digestive track of *Clostridium difficile* patients
44
*Clostridium difficile*: FMT - different types
- fecal microbiome transfer
- modified fecal communities
- fecal filtrates
45
*Clostridium difficile*: FMT - fecal microbiome transfer
- transferred entire gut microbiota
- microbes are minimally processed
46
*Clostridium difficile*: FMT - modified fecal communities
community used has enriched to depleted taxa
47
*Clostridium difficile*: FMT - fecal filtrates
only uses bacteriophages and metabolites
48
*Clostridium difficile* - bacterial monotherapy
- treatment of a bacterial infection with a single antibiotic drug
- targets one candidate species
49
*Clostridium difficile* - artificial microbial communities
using lab grown communities
50
*Clostridium difficile* - bacteriophages
using both targeted and untargeted
51
lingering concerns with LMT
- co-transfer of pathogenic microbes
- pneumonia from FMT delivered by tube through nose (nasogastric tube)
52
lingering concerns with LMT - co-transfer of pathogenic microbes
- transfer of multiple viral lineages through FMT has been documented
- but none of the groups infect humans
53
what is the future of FMT
- increasing the cultivability of bacteria to create synthetic bacterial communities
- better matching of donors and receptors
54
what is vaginal seeding
- procedure that involves transferring vaginal fluids from a birthing person to a newborn baby's skin, mouth, or nose
- usually performed after a C-section, when a baby doesn't come into contact with the vaginal bacteria
55
vaginal seeding - is this effective in restoring the microbiome
results are too inconsistent to make a claim
56
what are probiotics
live microorganisms which when administered in adequate amounts confer a health benefit to their host
57
probiotics - what conditions has research shown they alleviate
- Acne
- Bacterial vaginosis
- Clostridium difficile
- Dysbiosis
- Infectious diarrhea
- Inflammatory bowel disease
- Leaky gut
- Sinus infections
- Urinary tract infections
- Yeast infections
58
probiotics and Inflammatory Bowel Disease
- patients experiencing inflammatory bowel disease were given probiotics
- after 30 days, gut permeability decreased
- problem: don't know of if the bacteria had colonized the gut or not
59
what does the E. coli strain ECN do?
- induces expression of tight junction molecules ZO-1 and ZO-2
- keeps permeability down
60
probiotics and acne
- probiotics have equal efficiency as a common topical agent for acne (antibiotic)
- researchers have proposed to move towards probiotics instead of antibiotics
- problem: there is no control in the study
61
Challenges of probiotics
- Lack of regulation
- Most bacteria aren’t culturable
- Variable efficacy
62
Considerations to conquer regarding probiotics
- Enough live bacteria: 1-900B CFU (at least 50B!)
- Multiple compatible strains (at least 7)
- Safe record with regard to human use
- Check efficacy and research involved
- Shelf life (best ones need refrigeration)
63
what are Prebiotics
Non-digestible food or ingredients that promote the growth of beneficial microorganisms
64
prebiotics - examples of supplements
- green powders
- Fructooligosaccharides (FOS)
- Psyllium husk
65
supplements - green powders
mix of dried and ground vegetables, fruits, and herbs that are marketed as a way to increase your daily intake of fiber and other nutrients
66
supplements -Fructooligosaccharides (FOS)
- a type of carbohydrate that occur naturally in plants and are used as sweeteners and prebiotics (onions, garlic, asparagus, bananas, and artichokes)
- Most common one is Inulin
67
supplements - Psyllium husk
a soluble fiber that comes from the outer layer of the seeds of the Plantago ovata plant.
68
inulin supplements and bacteria
- promote the growth of some beneficial bacteria (Bifidobacterium spp)
- problem: don't know if the density affects health
69
what are Synbiotics
Mixture of probiotics and prebiotics
