Microbes, our other genome Flashcards
Learning objectives
- 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
Bacteria are the predominant life form on earth
- 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
- 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
Definitions
- Microbiota
– The micro-organisms present in a specific site - Bacteria
- Viruses
- Fungi
- Parasites
What influences the composition of microbial
communities?
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
Definitions
- Microbiome:
– Microbial community that occupies a well-defined habitat; or
– Collective genome of a microbial community
Determinants: intestinal microbiota and food intake
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.
Determinants: 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 a diverse ability to break down
different substrates. - Change in diet can alter the degradative activity
of the colonic microbiota.
– 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)
Dynamics of the microbiome
- 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
Dysbiosis
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
16S rRNA gene sequencing
How do we measure the microbiota and its function?
The two key sequence-based methods for measuring the microbiota
Measures of diversity
- 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
The gut microbiome: determinants and metabolic niches
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.
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.
Obesity and the gut microbiota
Microbiota, immune education and the hygiene hypothesis
- Microbiota shape immune homeostasis:
– Germ-free animals show deficiency in lymphoid organ development and
immune cell activity
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.
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.
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
Chemical transformation of xenobiotics by the human
gut microbiota
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
Chemical transformation of xenobiotics by the human
gut microbiota
- Gut microbes can also metabolize chemotherapeutic
agents, increasing or decreasing their effectiveness
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
Production of antibiotics by the human microbiota
Other members of the microbiota
- Fungi
– Can be identified and classified by sequencing a common nuclear
ribosomal internal transcribed spacer (ITS) region
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
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
