L7: Microbiome manipulation Flashcards
who is alexander Flemming
- discovered the Penicillium mould secreted an antibacterial substance
- he then named the substance Penicillin
what are antibiotics often used for?
- ear infections
- presumed Strep infections
- childbirth
antibiotic overuse - ear infections
most ear infections are viral and not bacterial
antibiotic overuse - childbirth
moms take antibiotics before birth to prevent newborn infections
why do we overuse antibacterial
it is bc we do not have the optimal tests to check to see if infections are bacterial or viral
what is the missing microbes hypothesis
- 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
what is the hygiene hypothesis
- 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
who is Barry Marshall
- 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
gastritis and peptic ulcer - prior to Mashall
- thought to be caused by access hydrochloric acid (HCl) and stress
- most common treatment was antacids or surgery
what is the problem with Marshall’s discovery
- 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
problem with Marshall’s discovery - what does Koch postulates tell us
a set of criteria that establish whether a microorganism is the cause of a disease
problem with Marshall’s discovery - what are the Koch postulates
- 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
problem with Marshall’s discovery - what is problematic about the postulates
- 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
how can H. pylori be present without making its host sick?
- it contains ureases
- enzymes that break down urea in gastric juice
- helps them resist acidic environments
what may result because of H. pylori?
- 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
who is Prof. Martin Blaser
- 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
Prof. Martin Blaser - what did his discovery regarding decline in H. pylori imply
- 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
Prof. Martin Blaser - what did he identify in H. pylori?
- CagA+ strains
- they induce enhanced host responses regarding development of atrophic gastritis, gastric cancer, and peptic ulcer compared with CagA- strains
explain the experimentally induced asthma experiment
- researchers used methacholine challenge induce asthma
- it is used to test for how responsive the lungs are
- and used as a diagnostic for asthma
experimentally induced asthma experiment - what are the 3 groups
- mice with no H. pylori
- mice that were given H. pylori as infants
- mice that were given H. pylori as adults
experimentally induced asthma experiment - what are results
mice that were exposed to H. pylori as infants had the most protective effects against asthma
how does H. pylori have protective effects - asthma
by inducing anti-inflammatory cytokines and suppressing pro-inflammatory cytokines
how does H. pylori have protective effects - protection from infections
activates immune responses
how does H. pylori have protective effects - hormonal
- H. pylori produces Lectin and Ghrelin
- it modifies hormones related to hunger and affects hormonal physiology in the stomach
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
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
germ-free mice - pros
- mice are free of all microorganisms in all tissues
- allows for exclusive colonization with defined microbes
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
germ-free mice: cons - developmental defects
- altered immune system
- increased stress response
- behavior
- nutritional deficiencies
- abnormal gut barrier
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
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
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
germ-free mice: obesity experiments - what does this imply
that microbes could be the most important factor in obesity
why are people now thinking about rewilding animals with microbes
a single course antibiotics can suppress as much as a third of your microbiota
rewilding with microbes - define coprophagoa
- eating fecal matter
- it is widely used in other animals to relieve gastrointestinal disorders
rewilding with microbes - define cow cannulation
transplanting gastric content from cow to cow to increase digestion
what is Clostridium difficile
- can cause diarrhea, colitis, and other intestinal conditions
- it is the leading cause of diarrhea associated with antibiotics
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
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
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
what’s the most common way to treat Clostridium difficile
antibiotics and antacids
Clostridium difficile - alternate methods of treatment
- fecal microbiome transplant (FMT)
- bacterial monotherapy
- artificial microbial communities
- bacteriophages
Clostridium difficile - fecal microbiome transplant
involves transferring stools from healthy donors into the digestive track of Clostridium difficile patients
Clostridium difficile: FMT - different types
- fecal microbiome transfer
- modified fecal communities
- fecal filtrates
Clostridium difficile: FMT - fecal microbiome transfer
- transferred entire gut microbiota
- microbes are minimally processed
Clostridium difficile: FMT - modified fecal communities
community used has enriched to depleted taxa
Clostridium difficile: FMT - fecal filtrates
only uses bacteriophages and metabolites
Clostridium difficile - bacterial monotherapy
- treatment of a bacterial infection with a single antibiotic drug
- targets one candidate species
Clostridium difficile - artificial microbial communities
using lab grown communities
Clostridium difficile - bacteriophages
using both targeted and untargeted
lingering concerns with LMT
- co-transfer of pathogenic microbes
- pneumonia from FMT delivered by tube through nose (nasogastric tube)
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
what is the future of FMT
- increasing the cultivability of bacteria to create synthetic bacterial communities
- better matching of donors and receptors
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
vaginal seeding - is this effective in restoring the microbiome
results are too inconsistent to make a claim
what are probiotics
live microorganisms which when administered in adequate amounts confer a health benefit to their host
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
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
what does the E. coli strain ECN do?
- induces expression of tight junction molecules ZO-1 and ZO-2
- keeps permeability down
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
Challenges of probiotics
- Lack of regulation
- Most bacteria aren’t culturable
- Variable efficacy
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)
what are Prebiotics
Non-digestible food or ingredients that promote the growth of beneficial microorganisms
prebiotics - examples of supplements
- green powders
- Fructooligosaccharides (FOS)
- Psyllium husk
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
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
supplements - Psyllium husk
a soluble fiber that comes from the outer layer of the seeds of the Plantago ovata plant.
inulin supplements and bacteria
- promote the growth of some beneficial bacteria (Bifidobacterium spp)
- problem: don’t know if the density affects health
what are Synbiotics
Mixture of probiotics and prebiotics
