Inhoudsopgave
The human gut microbiome in health and disease ................................................................................ 2
1. So you think you’re human ........................................................................................................ 2
1.1 Studying the gut microbiome using metagenomics.................................................................. 2
1.2 Enterotypes: cross-national clusters of gut flora composition ................................................. 3
2. Why do our microbiomes differ? ............................................................................................... 3
2.1 Identification of multiple dietary covariates ............................................................................. 4
2.2 Current theory: the flora “seeded” at birth................................................................................ 5
2.3 Microbiota-drug associations as primary confounder category................................................ 6
2.4 Age-related microbiome changes across lifespan.................................................................... 6
3. Why does it matter? .................................................................................................................. 6
4. Association ≠ causality ............................................................................................................. 8
5. Can improving the flora cure disease? ...................................................................................... 8
5.1 Gut flora influences brain development and behavior .............................................................. 9
1
, The human gut microbiome in health and disease
1. So you think you’re human
Bacteria = 1.000 times the number of humans on
earth → 1.3x the number of human cells you have
Gut microbiota: distribution → the highest
concentration of bacteria is found in the
gastrointestinal tract. The colon alone contains about
half a kilogram of bacteria (essentially functioning as a
“small organ”).
Your flora is your friend
• Food digestion
• Protection against pathogens
• Provides essential nutrients (e.g. vitamins)
- Bacteria not only help break down
food, but also produce substances (certain vitamins) that the own bodies cannot make.
• ‘Trains’ your immune system
- Teaching it to distinguish between harmless and harmful microbes, which is an important factor
in maintaining a balanced immune respons.
• Disturbance of flora is linked to major diseases
1.1 Studying the gut microbiome using metagenomics
Studying the gut microbiome using metagenomics
• Start with stool samples (fecal material), which contain a high proportion of gut bacteria.
• DNA sequencing on the bacterial community
• Metagenomic sequencing allows us to answer two main questions:
(1) Which microbes are present, and in what abundance?
(2) What are they capable of doing? (examining their genomes, we can infer their metabolic
pathways and functional potential)
Metagenomics provides access to the unculturable fraction of microbial life (i.e. for the first time, give access to
ALL organisms in a sample).
• Classical microbiology
- Relies on culturing microbes on a
petri dish.
- Only bacteria that thrive under the
specific conditions of the agar
plate (nutrients, temperature,
oxygen levels etc.) will grow.
- This introduces a strong bias,
because many gut microbes
cannot be cultured under
standard lab conditions.
2
The human gut microbiome in health and disease ................................................................................ 2
1. So you think you’re human ........................................................................................................ 2
1.1 Studying the gut microbiome using metagenomics.................................................................. 2
1.2 Enterotypes: cross-national clusters of gut flora composition ................................................. 3
2. Why do our microbiomes differ? ............................................................................................... 3
2.1 Identification of multiple dietary covariates ............................................................................. 4
2.2 Current theory: the flora “seeded” at birth................................................................................ 5
2.3 Microbiota-drug associations as primary confounder category................................................ 6
2.4 Age-related microbiome changes across lifespan.................................................................... 6
3. Why does it matter? .................................................................................................................. 6
4. Association ≠ causality ............................................................................................................. 8
5. Can improving the flora cure disease? ...................................................................................... 8
5.1 Gut flora influences brain development and behavior .............................................................. 9
1
, The human gut microbiome in health and disease
1. So you think you’re human
Bacteria = 1.000 times the number of humans on
earth → 1.3x the number of human cells you have
Gut microbiota: distribution → the highest
concentration of bacteria is found in the
gastrointestinal tract. The colon alone contains about
half a kilogram of bacteria (essentially functioning as a
“small organ”).
Your flora is your friend
• Food digestion
• Protection against pathogens
• Provides essential nutrients (e.g. vitamins)
- Bacteria not only help break down
food, but also produce substances (certain vitamins) that the own bodies cannot make.
• ‘Trains’ your immune system
- Teaching it to distinguish between harmless and harmful microbes, which is an important factor
in maintaining a balanced immune respons.
• Disturbance of flora is linked to major diseases
1.1 Studying the gut microbiome using metagenomics
Studying the gut microbiome using metagenomics
• Start with stool samples (fecal material), which contain a high proportion of gut bacteria.
• DNA sequencing on the bacterial community
• Metagenomic sequencing allows us to answer two main questions:
(1) Which microbes are present, and in what abundance?
(2) What are they capable of doing? (examining their genomes, we can infer their metabolic
pathways and functional potential)
Metagenomics provides access to the unculturable fraction of microbial life (i.e. for the first time, give access to
ALL organisms in a sample).
• Classical microbiology
- Relies on culturing microbes on a
petri dish.
- Only bacteria that thrive under the
specific conditions of the agar
plate (nutrients, temperature,
oxygen levels etc.) will grow.
- This introduces a strong bias,
because many gut microbes
cannot be cultured under
standard lab conditions.
2
