18 - Human Microbiome and Disease Flashcards

1
Q

Factors influencing microbial community composition

A
  • Environmental parameters filter diversity (e.g. oxygen tension, pH, temperature)
  • Interactions between microbes
  • Rapid evolution and speciation
  • Stochastic (unpredictable) forces
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2
Q

Interactions between microbes

A
  • Microbial communities comprise complex, interacting mixtures of bacteria, viruses, archaea, parasites, fungi
  • Competition and collaboration between microbes
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3
Q

Positive competition and collaboration between microbes

A

Cross feeding

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4
Q

Negative competition and collaboration between microbes

A

Bacteriocins that inhibit the growth of competing bacteria

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5
Q

Impacting factors on gut microbiome

A
  • Diet
  • Pharmaceuticals
  • Geography
  • Lifecycle stages
  • Birthing process
  • Infant feeding method
  • Stress
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6
Q

intestinal microbiota and food intake

A
  • 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
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7
Q

Example of geographical differences impacting microbiota

A
  • 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
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8
Q

Human microbiota between individuals

A
  • 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)
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9
Q
A
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10
Q

High bray curtis beta diversity score

A

More dissimilarity between samples

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11
Q

Bacterial succession

A

Predictable changes in bacterial community composition with age

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12
Q

Hysteresis

A

The phenomenon in which the value of a physical property lags behind changes in the effect causing it

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13
Q

Xenobiotic

A

A substance (often a synthetic chemical) that is foreign to the ecological system

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14
Q

Microbiota succession in early life

A
  • 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
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15
Q

When does colonisation first occur

A
  • 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)
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16
Q

Gut microbiome succession

A
  • Dominance of Enterobacteriaceae very early in life
  • Shift to balanced, stable microbiota over first 2 years
  • Breast fed (Bifidobacterium) vs formula fed (Bacteroides)
17
Q

Dysbiosis

A

An imbalance in a microbial community associated with disease

18
Q

Causes of dysbiosis

A
  • Bloom of pathobionts
  • Loss of commensals (e.g. antibiotic therapy) - often accompanied by pathen overgrowth
  • Loss of diversity (inflammatory bowel disease, HIV, diabetes)
19
Q

Example of loss of commensals

A

Clostridiodes difficile associated colitis

20
Q

Example of bloom of pathobionts

A

Enterobacteriaceae, in
inflammatory bowel disease

21
Q

Pathobiont

A

A potentially pathogenic organism which under normal circumstances lives as a symbiont

22
Q

Upper gastrointestinal tract vs lower

A

Acidic –> anaerobic and more neutral pH

23
Q

Positive effects of gut microbiome

A
  • Digestion and xenobiotic degradation
  • Immune system maturation and function
  • Brain development and behaviour
  • Protection and clearance of pathogens
24
Q

Dysbiosis of the gut microbiota and disease

A
  • Atherosclerosis
  • Allergies and autoimmune diseases
  • Diabetes
  • Inflammatory bowel disease
  • Neurodegeneration
  • Metabolic syndromes
25
Q

Short chain fatty acids (SCFA)

A
  • 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
26
Q

Examples of SCFA

A
  • Propionate
  • Acetate
  • Butyrate
27
Q

GLP-1 and PYY

A
  • Regulat appetite by acting on the
    hypothalamus
  • GLP-1 is also potent promoter of glucose dependent insulin secretion (insulin sensitivity, which protects against diabetes)
28
Q

L-carnitine and phosphatidylcholine

A
  • Constituents of red meat
  • Metabolised by intestinal bacteria, releasing TMA
  • TMA is converted by liver enzymes to TMAO, which promotes atherosclerosis
29
Q

Low mucus secretion of aberrant microbiota related to metabolic diseases

A

Results in ‘leaky’ epithelial barrier, which allows inflammatory PAMPs such as LPS to translocate, causing metabolic inflammation

30
Q

Microbiota related to metabolic health pathway

A

SCFAs > Increase mucus secretion > Increase methane production > decrease luminal pH > decreases blood glucose > increases energy expenditure > increases glucose stimulated insulin secretion

31
Q

Aberrant microbiota related to metabolic diseases pathway

A

Decrease mucus secretion > increase luminal pH > Increase Acetaldehyde > increase TMAO > Increase BG > increase Metabolic inflammation > decrease glucose stimulated insulin secretion

32
Q

What does TMA stand for

A

Trimethylamine

33
Q

What does TMAO stand for

A

Trimethylamine-N-oxide