HMB304 - Module 7 Collateral damage of antibiotics

what are the dominant phyla that make up the human microbiome?

-bacteriodes and firmicutes

what regularly defines a healthy gut microbiome?

- generally defined by high diversity and stability

what are factors that influence microbiome?

-dite

-lifestyle

-environment

-genetics

-mode of delivery

Describe broadly the main idea of microbial acquisition during birth.

-babies in the womb are sterile therefore born without microbiome allowing for oppurtunistic colonization during birth

what is the differences of mode dilivery and what affect they have on microbiome?

-vaginal delivery: micrbiome resembles mother beneficial vaginal and gut microbiome whcih is more diverse

C-section: microbiome resembles the mothers skin microbime less diverse

what is the relationship of HMO and microbiome acquisition?

-HMO human oligiosaccharides

-serve as food to nurture beneficial bacteria like bacteriodes in the babies preforming microbiome

-acts are renforcment

describe how the microbiome plays role in immune system education in early development?

1) microbiota heelp trian regulatory T-cells to prevent the immune systeem from targetting harmless bacteria

-prevents the immune system from becoming hyper active (prevents development of autoimmune related disorders)

when can immune education happen and what could the consequences be if it does not?

-immune education must happen in early life during window of opportunity 1-3 yrs

-disruption to microbiome development in early life can hinder immune and metabolic development

What is gut dysbiosis and what could the negative effects be?

Gut dysbiosis is the loss of beneficial bacteria and overall loss of diversity, resulting in overgrowth of harmful bacteria

- impacts overall health, creating widespread issues throughout the body

what is the situation in terms of preterm babies and administration of antibiotics?

-preterm babies have immature immune system and gut microbiome

-high risk of neonatal sepsis therefore require antibiotics to prevent neonatal sepsis delaying colonization of microbiome

what has the early administration of antibiotics to preterm babies led to in terms of health issues?

-antibotic thearpy in infanats has been linked to increased risk of necrotizing enterocolitis (NEC)

-leads to inflammation which leads to lack of blood flow leading to tissue death

what causes NEC and how does it relate to infants microbiome?

-NEC is linked to an immature immune and digestive system

- This causes inflammation, which results in less blood flow and eventually intestinal tissue necrosis

-the lack of an established microbiome lead to improper immune system education therefore hyperactivation of immune responses --> inflamation

what are potential treatments/actions to take to reduce the risk of NEC

1) giving baby prebiotics eg breastmilk that contians HMOs that promote growth of healthy bacteria

2) probiotics: can directly supplement the infant gut with benefical bacteria

3)postbioitcs: giving the baby beneficial metabolites that come from bacteria

what was the correlation between early life antibiotics in mice and asthma?

1) early-life vancomycin treatment in asthma challenged mice increased immune cell counts

2) OVA-specfic IgE was increased in neonates

3)airway was more hyperresponsive in OVA+vancomycin neonatal mice

overall found that vancomycin treated neonatal mice were significantly diseased

what did they find in changes in gut compostion when mice treated with vancomycin?

-significantly altered microbiome flora, depleted of bacteriodes which is linked to proper immune system education

-found to have effect on community composition independent of asthma

what are the sudgested link between asthma and early life antibiotic use?

sudggests theres a link between microbiome alterations as result of early life antibiotic use can result in increased suseptibiltiy to asthma this being result of improper training of the immune system (T-regs) by the microbiome

what are the three ways that a healthy diverse adult microbiome Protects its host from pathogens?

1) Colonizaqtion resistance: Nutrient space competion

2)active antagonsim

3)inhibitory molecules

how might colonization resistnace arise due to nutrient and space competion

-idea that beneficial bacteria take up space as well as consume large amount of ditary nutrients starving potential pathogenic bacteria preventing them from growing

- commensl bacteria can also adhere to intestinal wall act as layer of protection from paathogenic bacteria

how might active antagonsim protect from bad bacteria?

benefical bacteria can directly inhibit or kill thee pathogenic bacteria

- this can be profromed by directly delivering toxins through contact inhibition

-secreting toxic molecules

how might inhibitory molecules protect the microbiome from colonization of bad bacteria?

-microbial metabolites produced by commensals can have an inhibitory effect on pathogens

-e.g secondary bile salts, indoles, SCFAs

explain the example of colonization resistance against opportunistic bacteria such as C.diff.

1) undisterbed gut microbiota has benefical bacteria that are able to convert primary bile acids into secondary bile acids that inhibit C.diff growth

2)sialic-acid utilizing commensals convert sugar bound to intestinal epithilum consume them (nutrient deprevation)

overall make it an inhospitable environment for C.diff

How does antibiotic use induce dysbiosis in terms of C.diff infection?

1) andibiotics disrupt microbiota and depletes gut of bacteria able to convert primary bile acids into secondary bile acids

2) lack of secondary bile acids and more primary bile acids promotes the growth of C.diff

3) elimination of bacteria that consume sialic acid and other nutrients provides nutrients for C.diff to grow

what does C.diff infection do in terms of damage?

-C.diff releases toxins that damage the intestinal cell lining, causing inflamation

-toxins lead to diarrhea

-recurent infections are common due to hard to elimiante spores and dysbiosis cuased by antibiotics

what are the potential treatments for C.diff?

- fecal microbiota transplant, where they take stool from healthy donor and transfer to recipiant the idea is to restore the beneficial bacteria that was lost to restore microbiome that will control C.diff proliferation

what is the anitibiotic dominant effect?

idea that samples treated with same antibiotic going to have simalar microbiome compositions regarldless of sample site or OVA