Microbiota and Chemotherapy Flashcards
Microbial syst
humans=euk+bact.+archaebacteria+virus+parasite
Interactions between m/o and human can be anywhere o nsymbiosis (most are mulutalist -benefits e/o- but paratism (benefits/harm)/commentalism (nthg/benefits)
Holobioms: human gene and microbiome (euk host)
Microbiota: collection of ¢ of microbes
Microbiome: collection of gene from microbes
WHy we should care abt microbiota
Metabolize polysaccharides and omdulate immune system
Synthesize essentials vitamins and nutrients
Change animal behavior and mating preference
Make u unique: we are holobionts: unit of biological org composed of a host and its microbiota
Culture-based methods
Most bact. ¢ are unculturable with “GReat Plate Count Anomaly” because of non-appropriate nutrient and conditions
1-16S rDNA-based sequencing studies
2-Deep genomic sequencing studies “metagenomics”
3-mRNA sequencing: “metatranscriptomics”
4-Metabolomics
16S rDNA gene analysis
Phylogenetic marker found in all species (regions identical=slow-evolving and some are variable=fast-evolving and have unique seq in each bact.)
Specific primer allow us to target & amplify regions of interest found in most m/o of env
AFter PCR amp; seq regions and make comparisons with other species and its own species (pre-existing database)
Metagenomics
(Deep genomic sequencing studies “metagenomics”)
ADvanced methods for seq all genomic DNA in sample (human seq are removed w/ bioinfomatics tools)
Tell what gene are present
Metaboic act can be inferred
Microbial communities=site-specific
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ahd cluster by body site
site-sepfic (depends on the receptors)
Phylum-and genus- level classification of bact colonizing humans
Microbiota is dominated by 3-35 phyla
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Actinobacteria: predominate on skin
Lactobacillus: predominate vagina
Bacteroidete and Firmicute: gut
Streptococcus: mouth
Where we find them
Skin
Nose
Mouth/oral cavity
Urogenital tract
Penis
Gastrointestinal tract (Mostly anaerobe (rare facultive). mostly: bacteroidet, firmicute)
70% in colon
Skin and nose
Skin: Staphylocci, Streotococci, Diphtheroid (Adapted to UV and exposure)
Nose: Staphylococci, STreptococci
Mouth/oral cavity
No teeth: aerobe
Teeth: Surtout anaerobe (between teeth and gum)
Involved in totth decay
Linked to the gastrointestinal microbiota
Urogenital tract and penis
Vagina (varie with menstrual cycle): mainly lactobacillus (lactic acid=low pH production)+inhibit growth of other m/o
Penis: Mostly Pseudomanadaceae & Oxalobactericeae
Circumcisio reduce putative anaerobic (clostridia and prevotella)
Sexual act can alter microbial diveristy
Acquisition and development
foetus used to be considered sterile but acquire bcp microbes at bith (vaginal vs C-section)
Defined succession (depend on type of milk, env, exposure): establishment of facultative anaerobes (Enterobacteriaceae) and Bifidobacteria. AFter 6 months, obligate anaerobe predominate… at 3 years=adult-like microbiota
Changes affecting: travel, sickness, pregnancy, puberty…
BUT bacterial phyla remain stable over the course of month… species and streains that are more variable
Model to sudy microbiota
Mouse models: mammalian model with controlled cond and interv (genetics, diet…)
Germ-free=axenic=sterile=no microbiota (axenic mice obtained by hysterectomy rederivation and maintained in isolators)
Axenic and gnotobiotic mice
Gnotobiotic=all microbes are known (keep in sterile env)
Indiv microbes or pop are reintroduced into germ free or antibiotic treated mice
Anatomic and behavioral diff (mice=coprophagic)… only abt 30% is shared bact species
Microbiota-associated mice model give us means to determine causality and mechanisms of interaction
We are what we eat and obesity epidemic
Diveristy of the gut microbiota
More obesity… risk for diabete type II, cardiovascular disease, musculoskeletal disorder, and huge economic burden
Obeses indic have a distinct gut microbiome from lean indic but confounder (diet, env.genetic) exist
Exp… one obese and one lean (twins same gentics)=diff microbiota so we use mouse models (controlled genetics and diet) with leptin (hormone made by fat cells, that regulate amount of fat stored in the body, “satiety” hormone)and did variable region of 16S rDNA= obese and lean have diff microbiota
Gut microbiota and obesity: caus and effect
ratio of Riimcute: Bacteriodete were increased in in the obese/recipient mice
Other mice receiving feces from obese mic had more body fat inn 2 week despite no diff in amount of food eaten
Fene used to harvest E from carbohydrates higher in obese mice
Fecal calorimetry measurement showed that obese mice had less E left in their feces than lean mice
Tranlsation to human
GErm-free mice colonized with feces from twins (humans) discordant for obesity
Diet remain key: lean microbiota cant colonize well when mice are fed high fat/low fiber diets
Antibiotics and the gut microbiot
after 9 months after exposure, only one clindamycin-resistant strain detected…even afer 24 mo, diversity in gut remained low==
Antibiotic reduce gut microbiial diveresity (particul«rly disruptive during early childhood)
AT sub-therapeutic doses, antibiotic can promote weight gain
Unintended effect of antibiotics
can promote pathobiont (microbiata in healthy host… dont causae disease) expansion… Ex: Clostridoides difficile
C. difficile:
2% pop=healthy carriers
in env., spore former
Healthy microbiota: colonization resistance (inhibit other growht)
Highest risk fact: broad spectrum, antibiotic treatement…..
1st line treatement: disontinuation of antibiotic usage, Metronidazole or cancomycin course (better with probiotics)
