Microbes, our other genome Flashcards

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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

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  • 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
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  • 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

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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

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  • 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

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6
Q
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  • 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

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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

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8
Q

How do we measure the microbiota and its function?

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8
Q

The two key sequence-based methods for measuring the microbiota

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8
Q

Measures of diversity

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  • 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
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9
Q

The gut microbiome: determinants and metabolic niches

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9
Q
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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.

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9
Q
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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.

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11
Q

Obesity and the gut microbiota

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12
Q

Microbiota, immune education and the hygiene hypothesis

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  • Microbiota shape immune homeostasis:
    – Germ-free animals show deficiency in lymphoid organ development and
    immune cell activity
13
Q

Microbiota, immune education and the hygiene hypothesis

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  • ‘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
Q

Microbiota, immune education and the hygiene hypothesis

A
  • 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
Q

Microbiota, immune education and the hygiene hypothesis

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  • Revision of the hygiene hypothesis:
    – Protection from allergic diseases is mediated by early-life exposure to
    ‘healthy’ commensals rather than pathogens
13
Q

Chemical transformation of xenobiotics by the human
gut microbiota

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14
Q

Chemical transformation of xenobiotics by the human
gut microbiota

A
  • 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
Q

Chemical transformation of xenobiotics by the human
gut microbiota

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  • Gut microbes can also metabolize chemotherapeutic
    agents, increasing or decreasing their effectiveness
15
Q

Chemical transformation of xenobiotics by the human
gut microbiota

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  • 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
Q

Production of antibiotics by the human microbiota

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16
Q

Other members of the microbiota

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  • Fungi
    – Can be identified and classified by sequencing a common nuclear
    ribosomal internal transcribed spacer (ITS) region
17
Q

Other members of the microbiota

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  • 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
Q

Other members of the microbiota

A
  • 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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20
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