18 - Human Microbiome and Disease Flashcards
Factors influencing microbial community composition
- Environmental parameters filter diversity (e.g. oxygen tension, pH, temperature)
- Interactions between microbes
- Rapid evolution and speciation
- Stochastic (unpredictable) forces
Interactions between microbes
- Microbial communities comprise complex, interacting mixtures of bacteria, viruses, archaea, parasites, fungi
- Competition and collaboration between microbes
Positive competition and collaboration between microbes
Cross feeding
Negative competition and collaboration between microbes
Bacteriocins that inhibit the growth of competing bacteria
Impacting factors on gut microbiome
- Diet
- Pharmaceuticals
- Geography
- Lifecycle stages
- Birthing process
- Infant feeding method
- Stress
intestinal microbiota and food intake
- Most complex plant polysaccharides are not digested by humans and enter the colon as a potential food source for the microbiota
- Bacteria have diverse ability to break down different substrates
- Change in diet can alter composition and resulting degradative activity of colonic microbiota
Example of geographical differences impacting microbiota
- People of Japanese ancestry possess porphyranase enzymes in their gut microbiota which degrade sulfated polysaccharides found in edible seaweed (such as nori).
- They can therefore harvest energy from seaweed
Human microbiota between individuals
- HIghly variable within and between individuals
- Each person has a microbiota that is distinct and relatively stable (but may be upset due to AB or diet)
High bray curtis beta diversity score
More dissimilarity between samples
Bacterial succession
Predictable changes in bacterial community composition with age
Hysteresis
The phenomenon in which the value of a physical property lags behind changes in the effect causing it
Xenobiotic
A substance (often a synthetic chemical) that is foreign to the ecological system
Microbiota succession in early life
- Shaped by the availability of different nutrients
- In breastfed infants the gut microbiota is dominated by species (eg, Bifidobacteria) that metabolise human milk oligosaccharides.
- Shifts in composition and enrichment of bacterial functions related to carbohydrate metabolism and the biosynthesis of amino acids and vitamins
- By 2–3 years, a stable microbiota resembling that of the adults in the community
When does colonisation first occur
- Traces of bacterial DNA in placenta and amniotic fluid suggest prenatal colonization, but findings could be the result of contamination
- First major exposure during delivery (difference in microbiota of vaginally born neonates compared to Caesarean section)
Gut microbiome succession
- Dominance of Enterobacteriaceae very early in life
- Shift to balanced, stable microbiota over first 2 years
- Breast fed (Bifidobacterium) vs formula fed (Bacteroides)
Dysbiosis
An imbalance in a microbial community associated with disease
Causes of dysbiosis
- Bloom of pathobionts
- Loss of commensals (e.g. antibiotic therapy) - often accompanied by pathen overgrowth
- Loss of diversity (inflammatory bowel disease, HIV, diabetes)
Example of loss of commensals
Clostridiodes difficile associated colitis
Example of bloom of pathobionts
Enterobacteriaceae, in
inflammatory bowel disease
Pathobiont
A potentially pathogenic organism which under normal circumstances lives as a symbiont
Upper gastrointestinal tract vs lower
Acidic –> anaerobic and more neutral pH
Positive effects of gut microbiome
- Digestion and xenobiotic degradation
- Immune system maturation and function
- Brain development and behaviour
- Protection and clearance of pathogens
Dysbiosis of the gut microbiota and disease
- Atherosclerosis
- Allergies and autoimmune diseases
- Diabetes
- Inflammatory bowel disease
- Neurodegeneration
- Metabolic syndromes
Short chain fatty acids (SCFA)
- Produced by bacterial fermentation of indigestible polysaccharides
- Make epithelial barrier less permeable through increased mucus production and tight junction expression
- Also trigger release of hormones GLP-1 and PYY from enteroendocrine L cells
Examples of SCFA
- Propionate
- Acetate
- Butyrate
GLP-1 and PYY
- Regulat appetite by acting on the
hypothalamus - GLP-1 is also potent promoter of glucose dependent insulin secretion (insulin sensitivity, which protects against diabetes)
L-carnitine and phosphatidylcholine
- Constituents of red meat
- Metabolised by intestinal bacteria, releasing TMA
- TMA is converted by liver enzymes to TMAO, which promotes atherosclerosis
Low mucus secretion of aberrant microbiota related to metabolic diseases
Results in ‘leaky’ epithelial barrier, which allows inflammatory PAMPs such as LPS to translocate, causing metabolic inflammation
Microbiota related to metabolic health pathway
SCFAs > Increase mucus secretion > Increase methane production > decrease luminal pH > decreases blood glucose > increases energy expenditure > increases glucose stimulated insulin secretion
Aberrant microbiota related to metabolic diseases pathway
Decrease mucus secretion > increase luminal pH > Increase Acetaldehyde > increase TMAO > Increase BG > increase Metabolic inflammation > decrease glucose stimulated insulin secretion
What does TMA stand for
Trimethylamine
What does TMAO stand for
Trimethylamine-N-oxide
