Microbiomes Flashcards
What is the microbiome?
The community of symbiotic micro- organisms associated with a particular host or host body site/tissue, together with their environment
facts
- 1:1 human cells: microbiome
- approximately 160 ‘species’ in gut microbiome
- 2 – 20 million genes per human body (99.9% of the genetic potential in human body)
- Highely individualised (can identify humans with >80% accuracy from faecal microbe abundances)
- meta commnities with within and between host evolution
Human microbiota has 4 main phyla: (proportions vary per body site)
1. Actinobacteria – skin / nose
2. Bacteroidetes - gut
3. Firmicutes – external body + oral
4. Proteobacteria – gut + oral
Early life microbiome assembly
Most colonisation after birds (debate of placental transfer)
1) During birth
- C-section: gut microbiota shaped by skin and hospital surface (also requires antibiotics reducing diversity -> associated with allergies)
- Vaginal: gut microbiota shaped by vaginal microbes
2) Breast feeding
- Prebiotics: food for beneficial micro organisms growth (e.g. Human milk oligosaccharides catabolized by Bifidobacteria)
- Probiotics: Live beneficial miro organisms (e.g. Bifobacteria)
- Antibiotics: Supress certain microorganisms (e.g. IgA and Lactoferrin supress Enterobacteriaceae)
Mother microbiome also changes during pregnancy-> Lactobacillus (a Firmicute) dominance in vaginal microbiome may protect against UTIs during pregnancy
What effects microbiome later in life?
- behvaior (e.g. smoking)
- Environment (e.g. living in the country side)
- Diet (western diet w/ more fat, sugar and less fibre has lower microbiome diversity + more inflammation
- Antibiotic use
Microbiota succession throughout life
Primary succession: Children
- Alpha diversity increases
- Beta diversity decreases
Secondary succession: Adults
- Alpha and beta diversity are constant
- Alpha diversity can be knocked due to antibiotic use
Late succession: old age
- Alpha diveristy decreases
- Beta diversity increases
What determine our microbiome: environmental or genetic
Environmental> genetic
Study:
- comparing microbiome in inbreed strains of mice and mice with different diets
- More clustering of microbiomes due to diet rather than genomic simliairty
Functions of the microbiome
a) Defense -> Protect from infection + opportunist pathogens
- microbiota protects against incursion by pathogenic microorganisms via bacterial metabollism (e.g. nutrition competition over mucin), direct antagonism, Barrier maintanance (e.g. fatty acid production for epithelial cell), immunity stimulation, pH modulation (e.g. fermentation of dietry fibres)
Example: C.scindens and C.difficile
- C.s inhbit spore generation by C.d
- If C.s is removed, C.d can sporulate
b) Nutrition-> Breaks complex carbohydrates
- see obesity example
c) Synthesis of biomolceules -> Provide vitamins and amino acids
d) Influence immune system
- Immune-microbiota interactions in early life are critical in shaping maturation of the host’s immune system (disruption during developemeny have major impacts later in life-> e.g. allergens)
- Also important for developement fo Tregs to maintain homeostasis
- Microbiota free mouse defects: No Th17, fewer lymphocytes, reduced IgA antibodies
Nutrition: microbiome and obesity
Obesity develops from a prolonged imbalance of energy intake -> 500 million are clinically obese
Example: Western diets which are high in carbohydrates, sugars and fats lead to lower proportions of Bacteroidetes and higher proportions of Firmicutes -> Firmicutes increase breakdown of carbohydrates therefore uptake of fatty acids and storage of other molceules
Counter study: weight loss did not change the relative proportions of the Bacteroides spp, or the percentage of Firmicutes present -> relationship of ratio debated.
Microbiome memory: weight re-gain (yo yo effect)
- Diet obesity-induced alterations to the microbiome persist over long periods and enhance the rate of weight gain during secondary metabolic challenge.
Study: microbiome transfer
- Micorbiome from fat twin and thin twin transferred to mice and weight gain from same diet observed
Maintanance of immune homeostasis
The host must balance the immune response to respond to pathogens but not commensal microbes
Mucosal fire wall
- Keep bacteria (both commensal and pathogenic) away from epithelial surface.
- Mucus from goblet cells, AMPs from peneth cells, IgA from plasma cells
Lamina Propria
- underneath connective tissue containing lymphocytes as secondary defense if penetrate epithelila surface
Tregs
- regulatory T cells to supress adaptive response to commensal pathogens -> memory bank build up during develepement
- Treg activation lead to tolerogenic immune response -> immuno supressive
Microbiome and IBD
IBD: Crohn’s disease and ulcerative colitis (chronic, recurrent inflam disorder of intestines)
Interaction between microbiome and IBD:
1) IBD associated Mutations effecting mucosal firewalls against symbionts
- e.g. in Crohn’s, mutations in NOD2 impair AMP secretion & bacterial killing in lamina propria -> accumulation of bacteria and inflammation
2) Microbiota- immune interaction triggering IBD
- No single microbe has been clearly implicated
- Identify and remove?
3) dysbiosis
- IBD leads to dysbiosis (change in composition)
- This can perpetuate disease by affecting processes like metabolism (e.g. heart disease, obesity, T2 diabetes) or lead to innapropriate immune response
- e.g. decline in bacteria which are important for maintaining a strong epithelial barrier.
- Repair disymbiosis?
Application of microbiomes for health improvement
Prevent or treat acute infections (e.g. C. diff infection)
Restore a dysbiotic/depleted microbiome (e.g. prevent recurring obesity)
Reduce risk of chronic disease developing (e.g. IBD)
Optimise response to medical intervention (e.g. cancer therapy)
Support recovery from surgery or another medical intervention (e.g. restore microbiome post antibiotic use)
Improve general health (e.g. nutrition, mental health)
Methods for microbiome control
Faecal microbiome transplant: the administration of stool preparation obtained from a healthy donor to a diseased patient (recipient)
- Risk that stool contains pathogens/ bioactive compounds, non standardises, undefined
- Potential adminster own microbiome (e.g. stoolpre-surgery)
Probiotics: live microorganisms that, when administered in adequate amounts, confer a health benefit on the host
- Possibilty for precision probiotics personalised for individuals with containing multipe probiotics (allow complex biochemical pathways)
- Stopped by natural colonisation resistanse and production challenge
Postbiotics: Functionally bioactive molecules produced by microbes are administered to individuals. (e.g. amino aicds)
- More controilled and drug like but require regular intake
- Example: Flavonoids suplement removedeffect of previous high-fat diet on weight regain.
prebiotics: substrate that is selectively used by host microorganisms, conferring a health benefit (e.g. non digestible carbs)
- High dose required which can have negative effects and individualised response (depends on existing microbiota)
Diet: change food intake
- Example: long-term dietary fibre associated with decreased risk of IBD
Phage therapy: Targeted (species-specific) elimination of pathogen / pathobiont
- Example: Develop 5-phage cocktail targeting strains of Klebsiella pneumoniae (Kp2) associated with IBD severity
Overview
Microbiome is shaped by genetics and environment, developing throughout life
Uses
- Defense
- Nutrition
- Synthesis
- immune system developement
Key iteraction
- Microbiome + IBD
Epithelila lining essential for homeostatis maintanance
Microbiome control:
- post biotics
- Pre biotics
- Pro biotics
- Faecal transmission
- Phage therapy
- diet