19 - Probiotics & Prebiotics Flashcards
Probiotic and commensal organism mechanisms of colonisation resistance
- Enhancement of the epithelial barrier
- Increased adhesion to intestinal mucosa
- Inhibition of pathogen adhesion
- Competitive exclusion of pathogenic microorganisms
- Production of anti-microorgansim substances
- Modulation of immune system
Antibiotic therapy and the microbiota
- Although the composition of the gut microbiota varies between individuals, the community in each individual is relatively stable over time
- Treatment with antibiotics has short term (reversible) and long term (irreversible) effects on the microbiota
What has early life antibiotic therapy been associated with
- Type 1 diabetes
- Adiposity
- Risk of asthma
How to reverse the effects of antibiotics on the microbiota
- Probiotics
- Autologous faecal microbiota transplant (FMT)
- Spontaneous recovery
Clostridiodes difficile
- Antibiotics perturb the gut microbiota allowing subsequent overgrowth of C. difficile
- C. difficile spores germinate in the gut into vegetative cells that produce enterotoxin
- Results in colonic inflammation, diarrhoea and pseudomembranous enterocolitis
- FMT used as successful treatment
Microbiota shape immune homeostasis
Germ-free animals show deficiency in lymphoid organ development and immune cell activity
Hygiene hypothesis
- Lower incidence of hay fever and eczema in children with older siblings
- Proposed that infections in early childhood prevent atopy later in life
- Increased allergy in developed countries may be caused by ‘excessive’ personal hygiene
Revision of the hygiene hypothesis
- Commensal microbiota shifts the immune set point from T helper 2 (Th2) [associated with allergy] to Th1 response
- Protection from allergic diseases is mediated by early-life exposure to ‘healthy’ commensals rather than pathogens
Symbiotic gut microbiota
Operates with a functional intestinal epithelial cell barrier, with steady-state proportions of mucus, PRRs, antimicrobial peptides, and secretory IgA, which in turn contain the microbiota in the intestinal lumen
Symbiotic gut microbiota and the immune system
- Microbes at the epithelial surface are detected through PRRs.
- In a symbiotic gut, intestinal epithelial cells are desensitized by repeated exposure to small amounts of LPS.
- Induces epithelial cells to secrete molecules which promote the development of tolerogenic responses to the microbiota
- DCs support the development of Tregs to secrete IL10 and TGFb, which stimulate the production of commensal-specific IgA and decrease inflammation (tolerant immune response)
Microbiota derived SCFA
Promote the expansion and differentiation of Tregs
Dysbiosis and the immune system
- Associated with exposure of diverse PAMPs
- Pathobiont overgrowth and toxin production leads to the loss of barrier integrity and a breach in the intestinal epithelial cell barrier
- Translocation of bacteria and bacterial components triggers the intestinal immune system strongly through TLR activation
- Secretion of proinflammatory cytokines by DCs and macrophages fuels a Th1 and Th17 response and leads to secretion of high levels of IgG, increasing inflammation (dysregulated immune response)
Three compounds of xenobiotics
- Dietary compounds
- Industrial chemicals and pollutant
- Pharmaceuticals
- MIcrobiota can metabolise these substrates, humans cant
Artificial sweeteners
- Gut microbes hydrolyze the artificial sweetener cyclamate into cyclohexylamine.
- Cyclamate was banned after studies suggested that cyclohexylamine was carcinogenic
Microbiota and chemotherapy
- Gut microbes can metabolise chemotherapeutic agents, increasing or decreasing their effectiveness
- In antibiotic-treated or germ-free mice, tumour infiltrating myeloid-derived cells produced less cytokines and reactive oxygen species (which kill tumour cells) after chemotherapy
Methylmercury
- Accumulates in living organisms
- Threat to human health
- Faecal bacteria reduce methylmercury to inorganic mercury which is less toxic and excreted by the host
Example of production of antibiotics by human microbiota
The skin commensal S. lugdunensis produces a novel antibiotic (lugdunin) that inhibits the growth of S. aureus in vitro, and in a mouse skin infection model
Fungi microbiota
Identified and classified by sequencing a common nuclear ribosomal ITS region or 18S rRNA gene
Virus microbiota
Studied by enrichment and WMGS
Archaea microbiota
Methanogenic archaea are amongst the most abundant microorganisms in the human gut
Postbiotics
Functional bioactive compounds, generated during fermentation, which may be used to promote health (e.g. SCFA)
Untargerted microbiome directed interventions
- Exercise
- FMT
- Pre, pro and post biotics
- Nutrition
Targeted microbiome directed interventions
- Bio-engineered commensals
- Drugs targeting selected microbial metabolism
- Phage therapy
- CRISPR-Cas9
