Microbiota - Fan 2/25/16 Flashcards
new view of microbiome as an…
- ________
- composition
- interchangeable terms
microflora = microbiota = microbiome
idea of microbiome as an organ, that starts to develop during birth, undergoes growth/maturation
- 1014 organisms
- 1% euks, archaeons, viruses
- 99% bacteria
- composition can vary based on: age, diet, individ genetics
dysbiosis
abnormal microbiome that accompanies disease state
microflora distribution
- mouth: lots of bacteria
- stomach: almost all bacteria are killed; near sterile environment - only H. pylori
- duodenum/jejunum: slight increase in number of bacteria, but not much
- ileum: at lower end of ileum, by ileo-cecal sphincter, you get a huge jump in bacterial number
- colon: highest concentration of bacteria - mostly anaerobes, small quantity of aerobes and facultative anaerobes
- *bacteria account for 2/3 of fecal volume!!!
host microbial interactions
- commensalism
- mutualism: relatively new concept; recent studies challenge it
- parasitism: recent studies suggest that microbiota as a whole have negative impacts on human health
takehome message: human microbiota is a double-edged sword
key research tools for microbiota
metagenomics: ID of all microbes using high-throughput DNA seq
gnotobiotic animals: only contain certain known strains [compare physio diffs between different groups of same species]
- combined with the high throughput sequencing, this is a powerful technique to see whether human/animal microbiota are successful AND which orgs have been successfully transplanted
high sensitivity instrumentation for studying metabolism
host-microbiota interactions
benefits for microbes
- food
- indigestible components of food (ex. dietary fibers)
- aged gut epithelial cells and secreted proteins
- stable, protected environment
effects on human hosts
- benefits: many
- harms: many
role of microbiota in regulating GI tract devpt
(1960s study - mice made germ free using antibiotics)
compared to germ free mice, normal mice showed:
- thickening of muscle layer : improved motility
- recall pathway: gut bacteria stimulate nerve cells to release a growth factor for macrophages → feeds back onto ENS system, maybe in a way that provides neurocrines to muscle cells
- also a role for bacteria interacting with bile salts: if you inhibit bacterial-derived bile salt hydroxylases → inhibit gut motility
- stimulation of GALT (gut assoc lymphatic tissue)
- stimulating epi cell generation/turnover
- increasing cellularity of lamina propria
*
gut microbiota nutrition/metab
increase nutritional efficiency
- the gene pool of the microbiome is 150x the size of the human genome - has a lot more digestive enzymes to draw on
-
calorie salvage: supplies short chain FAs from otherwise indigestible foods
- ex. propionate, butyrate, acetate (produced by bacteria, used by host)
- supply essential a.a.s
- supply vitamins (K, B12, biotin, folic acid, pantothenate)
- aid in colonic conversion of BS to BA
- alters intrinsic metabolic machinery → more efficient nutrient uptake/util
gut microbiota: role in obesity/metabl syndrome
- dysbiosis in DM2 patients
- drop in butyrate-producing bacteria
- rise in opportunistic pathogens
- restoration of microbiota ever after gastric bypass
- artificial/noncaloric sweetners can favor prodiabetic gut microbes
- obese-prone mice stay lean after clearing out microbiota, become fat again after reintro
- thought: metab syndrome is regulated by host gene-microbiota interactions
- microbial biota are linked to diff DM1 pops in humans
gene/gut microbiota interactions: metabolic syndrome
TLR5 (Toll-like receptor 5, req for innate immunity) KO mice display:
- metabolic syndrome (hyperlipidemia, HTN, high insulin resistance, high adiposity)
- dysbiosis
tx with antibiotics reverses metab syndrome in TLR5-null mice
transplant of TLR5-null microbiota inter germ-free mice = metabolic syndrome
gut microbiota: role in malnutrition
- Malawi twins: one healthy, one with kwashiorkor
- kwashiorkor twin microbiota develop differently
- “transit maturation” of micriobiota once tx was started (peanut-based, ready-to-use food)
- regression once Malawi diet was resumed
- severe weight loss in gnotobiotic mice with the kwashiokor-twin microbiota and not with mice with the healthy-twin microbiota
gut microbiota in immunity
part of host’s innate immune system
- traditional idea: microbiota compete with pathogens for nutrients/adhesion sites, suppress pathogen growth
- produce antimicrobial factors [bacteriotoxins, bile acids, lactic acids, H2O2)
- toxin degradation
- general stim of immune fx (phagocytosis, antibody/cytokine production, GALT devpt)
- no Peyer’s patches in germ-free mice!
- M cells sample microbes and prsent antigens to lymphocytes
but might also be a pathogen helper!!!
- might be a role for use of antibiotics as tx for virus - knock out viral pathogen-helping microbiota!
consequence of antibiotic use
dysbiosis!!!
ex. C. diff infection
microbiota-associated conditions
- cancer (colorectal)
- inflammatory disease (IBD, arthritis)
- autoimmune disease (experimental demyelinating encephalitis = animal MS)
- mental health
- aging
mucosal defense: innate and acquired
ANATOMIC FACTORS
(upregulated by microflora)
- mechanical barrier: cont epithelium with tight jx between cells
- endocytosis/killing of pathogens (esp by epi cells, M cells)
- complement (pl protein that can lyse bacterial pathogens)
- granular leukocytes (neutrophils, macrophages, eosinophils)
- GALT
- other immune cells: NK cells
