Microbiomics Flashcards
How many bacterial cells can be found in our guts?
10^13
How many different bacterial genes can be found in the human microbiome? How many genes do humans have?
10^6 bacterial genes, compared to ~20.000 human genes
What is microbiomics? (definition)
Study of metagenomics of the microbiome to describe ecological communities of microorganisms
What is a metagenome? (definition)
Genetic material recoverd from environmental samples -> combined genomes of the microbiota & host
What are microbiota? (definition)
Collection of microorganisms
What is the microbiome? (definition)
Community of microorganisms and host
What is the method of metagenomics?
16S rRNA profiling = amplicon sequencing of the 16S rRNA target gene
What is α-diversity?
Diversity of different species within a sample: number of species*evenness
What is β-diversity?
Diversity/distance/dissimilarity between two samples
What is the gut brain axis?
The bidirectional communication between gut and brain
Though which means can the gut and brain communicate?
- Autonomic nervous system
- Neuroendocrine system
- Hypothalamic-pituitary-adrenal (HPA)-axis
- Immune system
- Metabolities & bacterial products
Which two parts of the autonomic nervous system are especially involved in the gut-brain axis?
- Vagal nerve
- Enteric nervous system
Which organ is also involved in the case that the gut and brain communicate via (bacterial) metabolites?
Liver
Which types of studies are currently being performed on the gut-brain axis? (4)
- Animal studies
- Small human studies
- Large cohort studies
- Randomized controlled trials
Which factors are commonly analyzed in studies focussing on the gut-brain axis? (7)
- Quality of life (QoL)
- Mood
- Anxiety
- Depression
- Alzheimer’s disease
- Parkinson’s disease
- Brain MRIs
Why is it difficult to study the interaction between the gut and the brain?
There are many intermediary & confounding factors
Translocation of certain compounds causes repetitive/depressed behaviour in animals. Addition of B. fragilis reversed this behaviour. What does this show?
That the composition of the microbiome determines which compounds can reach the brain and alter behaviour
What does the presence of B. fragilis in the gut do?
Maintains/restores epithelium impermeability by increasing claudin 8 expression = tight junction component
What is Poly(I:C)? What is its effect?
A synthetic nucleotide that induces gastrointestinal permeability
What is a downside of animal experiments concerning the gut-brain axis?
Experiments often performed with the same strain -> n=1 (not a representative sample)
Which bacterial species was found in the differential analysis between healthy & depressed individuals?
Coprococcus
What are the conclusions from current animal experiments on the gut-brain axis?
- Interventions are possible
- Animals don’t give self-reported data -> actual measurements (=advantage)
- Homogenous setting, increasing the chance that an observed effect is due to the intervention (=advantage)
- Each strain counts as one individual -> several strains need to be tested to draw conclusions
What does a PCoA analysis on a distance matrix show?
Clustering related to major phyla (closer = more related)
What can a PERMANOVA analysis tell us about the microbiome?
How much variance in the microbiome composition is determined by certain parameters (e.g. BMI) -> correlation between parameter & microbiome composition
What is usually the effect size in terms of explained variance by various factors?
<1% -> all factors only have a small impact, but all together they determine the microbiome composition
When the Bristol Stool Chart = higher, the α-diversity is [higher/lower]
Lower
In human cohort studies [no difference/a significant difference] in microbiome composition & distribution was found between healthy & depressed [children/adults]
There is a significant difference in the microbiome composition between healthy & depressed adults
This association was not found in children
Which bacterial gene functions seem to be an important difference between healthy and depressed individuals? (2)
- Dopamine synthesis
- Acetate synthesis
What is the main limitation of cohort studies of the microbiome?
Only shows cross-sectional data -> only associations, no causation
By which means can mechanisms & causality be investigated in microbiome research? (3)
- Longitudinal data
- Intervention studies
- Mendelian randomization
What is mendelian randomization?
Method using measured variation in genes to examine the causal effect of an exposure to an outcome
Can establish causal effect of an exposure (to a certain microbiome) and an outcome
Based on what are microbiomes randomized in mendelian randomization?
SNPs
