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
