The Human Microbiome Flashcards
Normal number of bacteria on skin
10^6/ml
Normal number of bacteria in colon
10^12/ml
Diversity of phyla in human microbiome
Narrow diversity. Only a few phyla of domain bacteria present.
Number of genes in human genome vs microbiome
10^4 vs 10^6 genes
Microbiomic digestion aid role
Degrade polysaccharides, make vitamin K
Microbiomic aid in development:
1)
2)
3)
1) Help epithelial cells mature
2) Angiogenesis
3) Lymphocyte development
Characteristics of majority of commensals
Bacteria, anaerobic
Main phyla of commensals: 1) 2) 3) 4)
1) Bacteroidetes
2) Firmicutes
3) Actinobacteria
4) Proteobacteria (relatively rare)
Proteobacteria
E. coli
Frequency of proteobacteria in microbiome
Relatively rare
Main aerobic bacterial commensals
Staphylococcus, streptococcus, lactobacillus
Is bacterial community structure stable?
Yes
Only changes at the extremes of life
Does microbiome change much between people?
Yes. Under 50% bacterial species shared between twins.
Most represented phyla in microbiome
Bacteroidetes, firmicutes
TLR expression on enterocytes
1)
2)
3)
1) Apical surface: TLR2, TLR4 weakly expressed
2) Cytoplasm: TLR3, 7, 9 expressed in endosomes
3) Basal surface: TLR5 expressed
Microbiomic compound that maintains epithelial integrity
SCFA (short-chain fatty acid)
How bacteroidetes avoid TLR binding
Express lipid A variants
How commensal bacteria skew adaptive immune system
Skew towards Treg, Th2
How pathogenic bacteria skew adaptive immune system
Skew towards Th1, Th17 (inflammatory)
Effects of germ-free environment: 1) 2) 3) 4)
1) Low IgA expression
2) Poorly-developed Peyers pathches
3) Few intra-epithelial lymphocytes
4) Prone to allergies (poor Treg, unwanted Th2 differentiation)
Specificity of commensal-induced IgA
Cross-reactive with pathogenic species
Role of glycocalyx in tolerance
Keeps commensals away from enterocytes.
Pathogenic bacteria can penetrate glycocalyx, therefore are recognised as pathogenic
Cytokines secreted in response to commensal bacteria
TGF-beta
Cytokines secreted in response to pathogens
IL6, IL12, TGF-beta
Disease directly associated with dysbiosis
1)
2)
1) Commensals cause infectious disease
2) Nutritional deficiency (malabsorption, vitamin deficiency)
Disease indirectly associated with dysbiosis
1) Obesity
2) Inflammatory bowel syndrome
3) Allergies
4) Autoimmune disorders
Disease caused by commensal clostridium difficile
Pseudomembranous colitis
Clostridium difficile carrier rate
Around 3% of population
Pseudomembranous colitis pathogenesis:
1)
2)
3)
1) Commensal flora altered (often with broad-spectrum antibiotics)
2) C. difficile overgrows in gut
3) Adheres to mucosal epithelium, produces cytotoxin, cell death, inflammation, bowel necrosis
Characteristic of microflora associated with repeated clostridium difficile infection
Greatly reduced diversity of flora (by analysis of 16S RNA)
GIT commensal infections at extra-intestinal sites. Common bacteria: 1) 2) 3) 4)
1) E. coli (UTI)
2) Klebsiella sp (wounds)
3) Enterobacteriaciae
4) Bacteroidetes sp.(wounds)
Inflammatory bowel disease susceptibility:
1)
1) Genes associated with NOD-like receptors and certain cytokines
2) Also associated with diet, reduced microflora diversity, appendectomy
Prebiotics
Dietary supplements that promote growth of commensal bacteria
Probiotics
Administration of therapeutic commensal bacteria, EG: lactobacillus
Vitamins from commensal bacteria
Vitamin K, biotin (B7), folate (B9)
Changes induced in host metabolism by commensals
1) Lipid metabolism
2) Short-chain fatty acid metabolism, associated with maintaining enterocyte function and differentiation
Phyla associated with obesity
Higher levels of actinomycetes, firmicutes.
Decrease in bacteroidetes
Associations with a high-fat diet
Increase in inflammatory responses, decrease in microflora diversity
Severe form of malnutrition
Kwashiorkor
Findings of Malawian Kwashiorkor study
1) Gene-content in faeces of Kwashiorkor-affected children fails to develop with age
2) Therapeutic food doesn’t sustain an initial change in gene content
3) Shows association between microflora composition and health
Effect of Kwashiorkor microbiota on metabolism
Chemicals produced that selectively inhibit TCA-cycle enzymes
–> Impaired cellular energy metabolism
Experimental treatment for Kwashiorkor
Faecal transplant
