12. Disease as an Imbalance of Microbes Flashcards
Define ‘dysbiosis’
- imbalance in microbial community associated with disease
- can be due to gain or loss of community members or changes in relative abundance of members
How to measure dysbiosis?
- DNA analysis of complex microbial populations
- involves sequencing 16S rRNA gene for bacteria
- metagenomics involves sequencing all DNA in sample and using bioinformatics to predict source and function of DNA sequences
… is one of the most diverse microbial communties in the body
gut microbiome
… to … species in gut microbiome
Variation between people is high/low
500-1000
high
Why are we still unclear what a healthy gut microbiome looks like?
- large differences in healthy individuals (genetic, environmental, lifestyle)
- differences in study parameters (experiemental design, bioinformatics analysis approaches)
- lack of large scale studies (30 mill people genome sequences vs 10,000 publicly available microbiome data sets)
3 things that influence gut microbiome
- mother
- environment
- lifestyle
How much of your gut microbiome is determined by environment?
20-25%
How does your mother influence your gut microbiome?
- first microbes you encounter are key
- acquired as you pass along birth canal
- breast feeding
- skin to skin contact
How does environment influnce gut microbiome?
- pets/rural upbringing
- drugs (antimicrobials)
How does lifestyle influence gut microbiome?
- diet (switch from eastern to western lifestyle can modify it and fibre consumption)
- urban vs indigenous lifestyle
Differences between microbiota have been linked to what factors?
- obesity
- colorectal cancer
- inflammatory bowel disease
- systemic conditions
Microbiome analysis measures … and therefore can’t be used for what?
- composition
- attribute certain organism to disease
- hard to compare studies too as diff experimental methods and bioinformatics
3 models of the gut microbiome in colorectal cancer
- model 1 is that the key microorganisms can drive tumorigenesis (F.nucleatum promotes cancer cell proliferation and inhibits anti-tumour immunity)
- model 2 is that collective mirobiota drives tumerigenesis (metabolism of fats by microbial communtiies releases carcinogens)
- model 3 is that key microbes shape microbiota (individual organisms can shape overall microbiota promoting model 2)
Explain IBD
Link to gut microbiome
- Chron’s disease and ulcerative colitis affects over 3.6 million people increasing in last few decades
- host genetics are key but less than 50% concordance with mono twins
- gut microbiome is a protagonist (no single causative organism, dysbiosis of microbial comms)
Difference between IBD and new-onset paediatric Crohn’s disease
- not changes in species present
- but the changes in metabolic functions in microbial community that drives disease
Changes in microbial composition in IBD
- decrease in alpha diversity
- decrease in bacteroides and firmicutes
- increase in gammaproteobacteria
- presence of E.Coli
- presence of fusobacterium
Changes in microbial function in IBD
- increase in auxotrophy
- increase in sulfate transport
- increase in amino acid transport
- increased oxidative stress
- decrease in amino acid biosynthesis
How do treatments target the microbiome?
- careful selection of antibiotics to minimise unwanted shifts in microbiota e.g avoids repeated use of single antibiotic
- repopulation of gut with healthy bacteria (pre and pro biotics, faecal microbiota transplantation)
- manipulation of microbiome from birth by vaginal seeding for C-section babies
Explain faecal microbiota transplantation
- encouraging results for relapsing C-difficile infection
- not so clear yet for IBD
Healthy oral microbiome is the … … community of humans with … to … species colonizing both … and … tissue
- second largest
- 400-700
- hard and soft
How do we acquire oral microbiota?
- oral bacteria from mother train fetal immunity
- vertical transmission during birth
- diet-breast feeding
- horizontal transmission - family members and pets
Dysbiosis of the oral microbiome drives what issues?
- periodontal disease
- caries
- oral cancer
- peri-implantitis
- mucosal diseases like leukoplakia and lichen planus
Periodontal disease is a … … disease
destructive inflammatory
Explain ‘non-specific plaque hypothesis’
- simple idea
- that plaque mass at gingival margin equates to disease status
Explain ‘specific plaque hypothesis’
- presence or an increase in specific pathogenic bacteria
- considered periodontal pathogen Socransky modified Kochs postulates
- pathogenicity of specific bacteria based on association with disease, treatment elimination, pathogenicity of animal models, induction of a host immune response and production of virulence factors
Explain ‘microbial shift hypothesis from specific plaque’
- decrease in number of beneficial commensal species an increase in number of specific pathogens associated with periodontitis
- identification of specific microbial groups within dental plaque
Why is dysbiosis sometimes not accurate for disease detection?
- putative periodontal pathogens like P.gingivalis are frequently found in healthy periodontal sites
- doesn’t mean they’re active players
Explain the ‘ecological plaque theory’
- subgingival environment dictates or selects specific microbial composition
- in turn this drives change from health to disease
Explain ‘keystone pathogen hypothesis’
- keystone pathogen supports and stabilises dysbiotic state
- triggers immune reaction
- even when present at low numbers
Explain polymicrobial synergy and dysbiosis model
- periodontitis is initiated by synergistic and dysbiotic microbiota
- fulfil different roles that converge and shape and stabilize disease-provoking microbiota
Explain dental caries
- most prevalent biofilm-dependent infectious disease
- causes tooth destruction leading to pulp infection and systemic infection
- through dysbiosis of supragingival plaque in a high sugar diet
Studies into caries
- small scale (8 with, 4 without)
- most species of bacteria common in caries and caries free - only a few associated with caries but acid production
- organisms most abundant in plaque showed diffs in caries and caries free (acidgenic and aciduric bacteria )
Explain extended caries ecological plaque hypothesis
- clinically sound enamel surfaces - mainly non-mutans strep and
actinomyces - add sugar and acidification enhances acidurance/genity of non-mutans bacteria and colonises more aciduric strains
- this acid-induced adaptation shifts demineralization/remineralization balance towards net mineral loss - dental caries
- prolonger acidic conditions means aciduric become dominant and promote greater demineralisation
