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Microbiomes > L7: Microbiome manipulation > Flashcards

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
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2
Q

what are antibiotics often used for?

A
  • ear infections
  • presumed Strep infections
  • childbirth
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3
Q

antibiotic overuse - ear infections

A

most ear infections are viral and not bacterial

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4
Q

antibiotic overuse - childbirth

A

moms take antibiotics before birth to prevent newborn infections

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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

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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
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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
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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
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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
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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
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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

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12
Q

problem with Marshall’s discovery - what are the Koch postulates

A
  1. organism can be isolated from every diseased host
  2. organism can be cultured in the laboratory
  3. the organism is re-introduced to healthy susceptible animal-model
  4. the organism can be isolated from the new host
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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
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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
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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
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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
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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
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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
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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
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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
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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

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22
Q

how does H. pylori have protective effects - asthma

A

by inducing anti-inflammatory cytokines and suppressing pro-inflammatory cytokines

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23
Q

how does H. pylori have protective effects - protection from infections

A

activates immune responses

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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
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25
Q

explain the co-adaptation of H. pylori and humans

A
  • there are benefits of having H. pylori
  • but benefits are prevalent in early life and declines with age
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26
Q

what are germ-free mice

A
  • a line of mice that are no bacteria and are kept in very specific conditions
  • used to conduct functionality testing of microbes
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27
Q

germ-free mice - pros

A
  • mice are free of all microorganisms in all tissues
  • allows for exclusive colonization with defined microbes
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28
Q

germ-free mice - cons

A
  • expensive
  • requires specialized equipment and training
  • new genotypes must be re-derived
  • not all experiments are feasible
  • developmental defects may make comparisons problematic
29
Q

germ-free mice: cons - developmental defects

A
  • altered immune system
  • increased stress response
  • behavior
  • nutritional deficiencies
  • abnormal gut barrier
30
Q

germ-free mice - obesity experiment

A
  • 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
Q

germ-free mice - obesity and microbiome transfer experiment

A
  • 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
Q

germ-free mice - obesity and gut microbiome transfer experiment

A
  • 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
Q

germ-free mice: obesity experiments - what does this imply

A

that microbes could be the most important factor in obesity

34
Q

why are people now thinking about rewilding animals with microbes

A

a single course antibiotics can suppress as much as a third of your microbiota

35
Q

rewilding with microbes - define coprophagoa

A
  • eating fecal matter
  • it is widely used in other animals to relieve gastrointestinal disorders
36
Q

rewilding with microbes - define cow cannulation

A

transplanting gastric content from cow to cow to increase digestion

37
Q

what is Clostridium difficile

A
  • can cause diarrhea, colitis, and other intestinal conditions
  • it is the leading cause of diarrhea associated with antibiotics
38
Q

Clostridium difficile - explain the bacteria

A
  • gram positive, obligate anaerobe
  • colonization in hospitals or via healthy care workers
  • a diverse microbiome is key against C. difficile colonization
39
Q

Clostridium difficile - why is a diverse microbiome needed to fight it

A
  • 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
Q

Clostridium difficile - what will happen after antibiotic overconsumption

A
  • 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
Q

what’s the most common way to treat Clostridium difficile

A

antibiotics and antacids

42
Q

Clostridium difficile - alternate methods of treatment

A
  • fecal microbiome transplant (FMT)
  • bacterial monotherapy
  • artificial microbial communities
  • bacteriophages
43
Q

Clostridium difficile - fecal microbiome transplant

A

involves transferring stools from healthy donors into the digestive track of Clostridium difficile patients

44
Q

Clostridium difficile: FMT - different types

A
  • fecal microbiome transfer
  • modified fecal communities
  • fecal filtrates
45
Q

Clostridium difficile: FMT - fecal microbiome transfer

A
  • transferred entire gut microbiota
  • microbes are minimally processed
46
Q

Clostridium difficile: FMT - modified fecal communities

A

community used has enriched to depleted taxa

47
Q

Clostridium difficile: FMT - fecal filtrates

A

only uses bacteriophages and metabolites

48
Q

Clostridium difficile - bacterial monotherapy

A
  • treatment of a bacterial infection with a single antibiotic drug
  • targets one candidate species
49
Q

Clostridium difficile - artificial microbial communities

A

using lab grown communities

50
Q

Clostridium difficile - bacteriophages

A

using both targeted and untargeted

51
Q

lingering concerns with LMT

A
  • co-transfer of pathogenic microbes
  • pneumonia from FMT delivered by tube through nose (nasogastric tube)
52
Q

lingering concerns with LMT - co-transfer of pathogenic microbes

A
  • transfer of multiple viral lineages through FMT has been documented
  • but none of the groups infect humans
53
Q

what is the future of FMT

A
  • increasing the cultivability of bacteria to create synthetic bacterial communities
  • better matching of donors and receptors
54
Q

what is vaginal seeding

A
  • 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
Q

vaginal seeding - is this effective in restoring the microbiome

A

results are too inconsistent to make a claim

56
Q

what are probiotics

A

live microorganisms which when administered in adequate amounts confer a health benefit to their host

57
Q

probiotics - what conditions has research shown they alleviate

A
  • Acne
  • Bacterial vaginosis
  • Clostridium difficile
  • Dysbiosis
  • Infectious diarrhea
  • Inflammatory bowel disease
  • Leaky gut
  • Sinus infections
  • Urinary tract infections
  • Yeast infections
58
Q

probiotics and Inflammatory Bowel Disease

A
  • 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
Q

what does the E. coli strain ECN do?

A
  • induces expression of tight junction molecules ZO-1 and ZO-2
  • keeps permeability down
60
Q

probiotics and acne

A
  • 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
Q

Challenges of probiotics

A
  • Lack of regulation
  • Most bacteria aren’t culturable
  • Variable efficacy
62
Q

Considerations to conquer regarding probiotics

A
  • 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
Q

what are Prebiotics

A

Non-digestible food or ingredients that promote the growth of beneficial microorganisms

64
Q

prebiotics - examples of supplements

A
  • green powders
  • Fructooligosaccharides (FOS)
  • Psyllium husk
65
Q

supplements - green powders

A

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
Q

supplements -Fructooligosaccharides (FOS)

A
  • 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
Q

supplements - Psyllium husk

A

a soluble fiber that comes from the outer layer of the seeds of the Plantago ovata plant.

68
Q

inulin supplements and bacteria

A
  • promote the growth of some beneficial bacteria (Bifidobacterium spp)
  • problem: don’t know if the density affects health
69
Q

what are Synbiotics

A

Mixture of probiotics and prebiotics

Microbiomes (17 decks)

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