Microbes, our other genome Flashcards

(37 cards)

1
Q

Learning objectives

A
  • Define the terms microbiome, microbiota, dysbiosis
  • Describe the determinants of microbiome composition
  • Understand the methods for measuring microbiome composition
  • Describe different measures for microbiome diversity
  • Describe the role of the gut microbiota in human health and
    disease
  • Understand the hygiene hypothesis in relation to the microbiome
  • Describe the role of the microbiome in metabolizing xenobiotics
  • Describe the role of the microbiome as a source of antimicrobial
    compounds
  • Describe the non-bacterial components of the microbiome, and
    how we measure them
  • Describe interventions to manipulate the microbiota
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2
Q

Bacteria are the predominant life form on earth

A
  • Stars in the universe vs. bacteria on earth?
    – 5x1030 bacteria vs. 1x1024 stars
  • Bacteria or human cells in the human body?
    – 3.8x1013 bacteria vs 3.0x1013 human cells
  • Total weight of all humans vs. all bacteria on earth?
    – Bacterial mass 100 million-fold greater than human mass
  • Bacteria have an evolutionary history of 4 billion years
    – Modern humans < 100,000 years
    – Bacteria changed the earth’s atmosphere (cyanobacteria
    created the Great Oxygenation Event)
    – Marine microbial communities are responsible for half of
    the oxygen produced on earth
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3
Q
A
  • Competition and collaboration between microbes
    – positive: cross-feeding
    – negative: bacteria produce antibiotics (bacteriocins) that inhibit the
    growth of competing bacteria
    – Stochastic (unpredictable) forces
  • e.g., dispersal, dormancy
    – Rapid evolution
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3
Q

Definitions

A
  • Microbiota
    – The micro-organisms present in a specific site
  • Bacteria
  • Viruses
  • Fungi
  • Parasites
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3
Q

What influences the composition of microbial
communities?

A

Interactions between biological / physical / chemical
environment
– Environmental parameters
* e.g., oxygen tension, pH, temperature, energy sources
– Interactions between microbes
Interactions between biological / physical / chemical
environment

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3
Q

Definitions

A
  • Microbiome:
    – Microbial community that occupies a well-defined habitat; or
    – Collective genome of a microbial community
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4
Q

Determinants: intestinal microbiota and food intake

A

People of Japanese origin can harvest energy from seaweed, whereas most other
people cannot.
* Japanese people have Bacteroidetes bacteria in their gut microbiota which
contain porphyranase enzymes which degrade sulfated polysaccharides found
in edible seaweed (such as nori).
* Marine Bacteroidetes bacteria which grow on seaweed possess similar
porphyranase enzymes.
* Transfer of genes from marine Bacteroidetes bacteria on nori was the likely
origin of enzymes to the Japanese human gut microbiota.

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4
Q

Determinants: 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 a diverse ability to break down
    different substrates.
  • Change in diet can alter the degradative activity
    of the colonic microbiota.
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5
Q
A

– Environmental parameters
* e.g., oxygen tension, pH, temperature, energy sources
– Interactions between microbes
* Microbial communities typically comprise complex, interacting
mixtures of bacteria, viruses, archaea and micro-eukaryotes (parasites,
fungi)

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5
Q

Dynamics of the microbiome

A
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6
Q
A
  • Loss of commensals (e.g., antibiotic therapy)
    – Often accompanied by pathogen/pathobiont overgrowth,
    e.g., Clostridiodes difficile associated colitis
  • Loss of diversity
    – Low bacterial diversity has been documented in association
    with inflammatory bowel disease, HIV and type 1 diabetes
    mellitus
    *pathobiont=a potentially pathogenic organism which under normal circumstances lives as a symbiont
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7
Q

Dysbiosis

A

An imbalance in the microbial community associated with disease

  • Bloom of pathobionts*
    – Overgrowth of members of the commensal microbiota, e.g.,
    Enterobacteriaceae, in inflammatory bowel disease
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7
Q

16S rRNA gene sequencing

A
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8
Q

How do we measure the microbiota and its function?

A
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8
Q

The two key sequence-based methods for measuring the microbiota

A
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8
Q

Measures of diversity

A
  • Diversity estimates incorporate information regarding
    species richness and evenness
    – Alpha diversity is a measure of the mean diversity within a
    sample
    – Beta diversity is a measure of diversity between samples
9
Q

The gut microbiome: determinants and metabolic niches

9
Q
A

Alpha Diversity = richness and evenness of individuals within a site/sample. For example
in the figure below, Alpha Diversity of Site A = 7 species, Site B = 5 species, Site C = 7
species.

9
Q
A

Beta Diversity = diversity between sites/samples. In the example below, the
greatest Beta Diversity is observed between Site A and C with 10 species that differ
between them and only 2 species in common.

11
Q

Obesity and the gut microbiota

12
Q

Microbiota, immune education and the hygiene hypothesis

A
  • Microbiota shape immune homeostasis:
    – Germ-free animals show deficiency in lymphoid organ development and
    immune cell activity
13
Microbiota, immune education and the hygiene hypothesis
* ‘Hygiene hypothesis’ (David Strachan, 1989): 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.
13
Microbiota, immune education and the hygiene hypothesis
* Discovery by Charles Janeway, that immune cells have pattern recognition receptors (PRR) which sense conserved microbial molecules (PAMPS, found on pathogens and commensals) – Commensal microbiota shifts the immune set point from T helper 2 (Th2) [associated with allergy] to Th1 response.
13
Microbiota, immune education and the hygiene hypothesis
* Revision of the hygiene hypothesis: – Protection from allergic diseases is mediated by early-life exposure to **‘healthy’ commensals rather than pathogens**
13
Chemical transformation of xenobiotics by the human gut microbiota
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Chemical transformation of xenobiotics by the human gut microbiota
* Although many artificial sweeteners are poorly metabolized by humans, studies demonstrate that they are susceptible to microbial transformation. – Gut microbes hydrolyze the artificial sweetener cyclamate into cyclohexylamine. Cyclamate was banned in the United States after studies suggested that cyclohexylamine was carcinogenic
15
Chemical transformation of xenobiotics by the human gut microbiota
* Gut microbes can also metabolize chemotherapeutic agents, increasing or decreasing their effectiveness
15
Chemical transformation of xenobiotics by the human gut microbiota
* Methylmercury accumulates in living organisms, posing a threat to human health – Faecal bacteria reduce methylmercury to inorganic mercury which is less toxic and excreted by the host
16
Production of antibiotics by the human microbiota
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Other members of the microbiota
* Fungi – Can be identified and classified by sequencing a common nuclear ribosomal internal transcribed spacer (ITS) region
17
Other members of the microbiota
* Viruses – Far more challenging to identify the variety of viruses in a sample due to the absence of conserved genes – Bacteriophages are probably the most abundant members of the microbiome – Need to use whole metagenome sequencing or culture to discover viruses
18
Other members of the microbiota
* Archaea – Recent interest due to discovery of previously undetected humanassociated archaea – Methanogenic archaea are amongst the most abundant microorganisms in the human gut – Can be measured by sequencing 16S rRNA genes
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