Commensal Microbiota Flashcards
(26 cards)
Microbiome
the collection of genomes of the microbiota as well as their products and the host environment.
Commensal microbiota
Community of microorganisms which colonize and symbiotically exist on the surfaces of the barrier tissues of our body
(epidermis and internal mucosa).
Human microbiome project
National Institutes of Health (NIH)
5000 species identified
20 million unique microbial genes sequenced.
Role of microbiota in health
Regulating structural integrity of mucosal barrier.
Biosynthesis of bioactive molecules: vitamins, amino acids, lipids
Provide the enzymes required for the metabolism and the extraction nutrients.
Protection from exogenous pathogens: secretion of anti-microbial compounds.
Development and maturation of the immune system.
Development of microbiota
Initial colonization: after birth – origin: maternal microbiota (depending on delivery method)
Age 3: stable, adult- like composition
Early microbiota
Links to antibody-dependent immunity through breastfeeding
Key role in development of intestinal architecture
Development of immune system:
— number of immune cells (intra-epithelial lymphocytes, innate lymphoid cells, Th17cells)
— composition of the intestinal antibody repertoire (IgA, IgE)
Factors affecting the composition of the gut microbiota
Birth mode
Breast feeding
Diet
Geography
Exercise
Drugs
Ageing
Disease
Skin microbiota
Cutibacterium acnes & Staphylococcus epidermidis:
the fight against pathogenic bacteria
Nutrient competition
Production of bacteriocins
Induce production of anti-microbial peptides (AMPs) by the skin cells
Lower the pH of the skin: conversion of glycerol to short chain free fatty acids (FFAs)
Inhibition of biofilm formation
Immune system desensitization (TLRs)
Enhancement of innate immunity: pro-inflammatory cytokines
Pathogenic condition of skin
Dysbiosis
prevailing virulent species
Cutibacterium acnes
Staphylococcus epidermidis
Staphylococcus aureus
Mucus layer of hyperglycosylated mucin (MUC2)
physical barrier
delivers tolerogenic signals to dendritic cells –controls immunogenicity
Epithelial layer of gut
Tight junctions – Transepithelial permeability
Microbial metabolites (eg. indole) fortify the epithelial barrier: upregulation of tight junctions and cytoskeletal proteins
Microbiota promote maturation of the immune system
Gut microbiota- bidirectional communication with the immune system
Productions of Short-chain Fatty Acids (SCFAs) (eg. acetates, proprionates, butyrates) – barrier integrity
Microbiota-derived compounds:
-anti-inflammatory signatures
-immune cell differentiation
Pattern recognition receptors (eg. Toll-like Receptors) sense microbial signal regulate the amount of commensal microbes
Host-induced productions of antimicrobial peptides and IgA: barrier integrity and shape the microbiota composition
Innate immune response
Dendritic cells, monocytes, macrophages, lymphoid cells
Adaptive immune response
B and T cells
Microbiota stimulate production of protective IgA - anti-inflammatory effect and shaping the microbe composition
Microbiota composition signals the activation of differentiation of T-cell subtypes ie. effector T-cells, regulatory T-cells
How can metabolic disorders of the gut be reversed
High fibre diet
Administration of commensal akkermansia muciniphila
Targeted immunization
Research using Germ Free animal models
GFs: defects in lymphatic tissues – decreased B & T lymphocytes
Transplantation of intestinal/fecal microbiota from normal mice: restoration of immune system
Vitamin K and the gut microbiome
Vitamin K: required for the production blood clotting factors.
Sources: diet and gut microbiome (large intestine).
Antibiotics can lead to reduced vitamin K levels & bleeding
Vitamin K supplements: prolonged antibiotic therapy; newborn injection at birth
Gut-brain axis
IBS & IBD occur in conjunction with high anxiety levels
Probiotics minimize anxiety
Chronic liver disease linked to hepatic encephalopathy (decreased cognition; autism-like behavior; increased SCFA)
Antibiotic treatment – restore cognitions
Stress linked to gut microbiota composition:
GF mice: high anxiety levels & affected brain function
Colonization – decreased anxiety
Role of gut microbiota in metabolic syndromes
High fat and sugar-intake lead to gut dysbiosis leads to intestine colonization with enterobacteria (eg. E.coli)
Colibactin induced DNA-damage of of intestine cells – pro-tumorogenic activity
Different microbiota composition between lean and obese individuals (Bacteroidetes vs Firmicutes)
Promotion of inflammation & hormonal regulation:
- insulin resistance
- suppressed secretion of anti-hunger hormones
- suppressed secretion of anti-depressive neurotransmitters
Antibiotic against obesity-associated bacteria or prebiotics (nondigestible sugars) or probiotics
Diet linked to metabolic syndromes
Refined grains
Red meat
Saturated fats
Sugary drinks/sweets
Cancer protective and tumour promoting effects
Bacterial toxins: DNA damage or indirect effect on genomic integrity and DNA repair
Binding and stimulation of epithelia proliferation
Immunomodulation: production of chemokines and cytokines
Stimulate senescence to epithelial and fibroblastic cells (butyrate-producing bacterial)
Breach of mucus barrier and epithelial integrity
Disease treatment - developing personalised approaches
Microorganism supplementation or augmentation
Microorganism suppression
Metabolite modulation
Microorganism supplementation or augmentation
Beneficial bacteria promotion
Engineered microorganisms
Microbiome transplantation
Microorganism suppression
Phage therapy
Predatory bacteria
RNA-guided nucleases
