NUTRITION AND
HEALTH: HUMAN
MICROBIOME
MIB-51301
,Module 1: The Human
Microbiome
1.1 Beneficial microbes
Microbiota take up space and thereby preventing colonization by invaders
o Systems without microbiota, like newborns and germ-free animals, are very
vulnerable to infectious micro-organisms
Microbiota stimulate our immune system and protect against auto-immune diseases:
symbiosis
o The immune system cannot maturate when it’s not exposed to micro-
organisms and compounds in our gut immune system starts attacking non-
pathogenic substances like food particles or own body cells (auto-immune
diseases)
o Symbiosis helps the immune system to figure out which microbes and
particles the immune system can trust and which it should attack
Microbes are involved in the induction, training and functioning of the
immune system.
Microbiota play an important role in food digestion
o Produce substances that influence our metabolism
Fermentation leads to SCFA that can be used as energy source
Increased yield from our food
Produce vitamins that we can absorb and use
o Can influence our feeling of hunger, weight gain or weight loss
Coprophagic: animals that are pure vegetarian and eat their own feces because it is the only
way to consume essential vitamins
Antibiotics also kill good microbiota and excessive/unnecessary use has been associated with
risk factors for obesity, diabetes type 2 and autoimmune diseases.
Hygiene hypotheses: lack of early childhood exposure to all kinds of microbes, infectious
agents and parasites suppresses the natural development of the immune system.
1.3 How to study the Microbiome
Microscopy
o To understand cause of infectious diseases
Culturing
o You isolate a type of bacterium and grow it on a specific media to find out the
characteristics of the bacteria
Not all bacteria can be cultured yet is the right medium is unknown
o Also, to test if a bacterium is susceptible to certain antibiotic
Culture independent techniques: DNA, RNA, proteins or metabolites
o Finding out what they are capable of doing (in our bodies)
, Can give an idea about food digestion, vitamin production
o 16s rRNA gene: found in all bacteria and archaea but not in eukaryotes
Conserved/common region: to pinpoint the gene
Variable/specific part: identify species
1.3.2 Omics Approaches
Omics techniques: collective characterization and quantification of pools of biological
molecules: study millions of molecules in a snapshot
- Each analysis gives you a snapshot of the information/composition at a certain time
point of measurement.
- Generate big databases of molecular data form the microbiome
16S rRNA DNA profiling uses primers that amplify the 16S rRNA gene of all microbes
to create a database of DNA sequences
o Community profiling: determining the abundance of each kind of microbe,
community diversity
Microbes that are most abundant will be found back the most in the
sequence reads
o The sequence information will tell you:
Which DNA (and thus what microbes) is there
Which microbes are very well represented and which are present in
low numbers.
NOT the function
Metagenomics: Uses a set of primers that can amplify any gene of any
microorganism
o To study the genetic potential of the microbiome we can use the information
of the complete genomes of all microbes in a fecal sample
o Advantages
Reads can be grouped in batches, depending on what information you
are interested in
The genes can be used to assemble genomes and extrapolate
complete genomes from your fecal sample or discover complete
genomes of bacteria that are not yet cultured.
The genome information can be used to understand the needs of the
microbe and can help design a culture media for an uncultured
microbiota member
Compare the complete set of genes of the microbiome between
groups of individuals: helps to understand to actual functional
involvement of the microbiome in states of disease
The creation of big databases of microbial products through the sequencing can be
done for DNA, RNA, proteins and metabolites.
Each of these different approaches will give you clues about the function of the
microbiota.
, o It will also tell you what is most abundant, and if there are differences
between samples.
Note: generated results are only snapshots of a certain sample point, and the amount of
data needs to be taken into account to understand if the complete microbial community is
represented
Shotgun sequencing describes the gene content; the long stretch of the nucleotides adenine
(A), cytosine (C), guanine (G) and thymine (T).
1.4 Microbiota for Health
1.4.1 Microbiome Research and Causality
Causality: A influences B, the relationship between a cause and an effect
Correlation: A and B show a linear relationship
Association: connection between two factors, however it is possible that we miss other
factors that are involved.
The main challenge is to figure out the changes in the gut microbiome actually play a
role in disease.
o When a causative link has been proved, we might be able to modulate the gut
microbiota to diagnose, prevent or cure diseases
Example: A fecal microbiota transplant of a healthy gut microbiome composition can restore
the balance and get rid of the Clostridium difficile.
Approaches to find causative relationships between the gut microbiome and health:
Germ-free mice: mice that were never in contact with microbes
o Exposing these mice to micro-organisms, we can test the effect of the specific
bacteria on e.g. metabolism, digestion or immune response
o Don’t give us a decisive answer on the effectivity of a potential treatment in
which we influence the gut microbiome clinical trials needed
HEALTH: HUMAN
MICROBIOME
MIB-51301
,Module 1: The Human
Microbiome
1.1 Beneficial microbes
Microbiota take up space and thereby preventing colonization by invaders
o Systems without microbiota, like newborns and germ-free animals, are very
vulnerable to infectious micro-organisms
Microbiota stimulate our immune system and protect against auto-immune diseases:
symbiosis
o The immune system cannot maturate when it’s not exposed to micro-
organisms and compounds in our gut immune system starts attacking non-
pathogenic substances like food particles or own body cells (auto-immune
diseases)
o Symbiosis helps the immune system to figure out which microbes and
particles the immune system can trust and which it should attack
Microbes are involved in the induction, training and functioning of the
immune system.
Microbiota play an important role in food digestion
o Produce substances that influence our metabolism
Fermentation leads to SCFA that can be used as energy source
Increased yield from our food
Produce vitamins that we can absorb and use
o Can influence our feeling of hunger, weight gain or weight loss
Coprophagic: animals that are pure vegetarian and eat their own feces because it is the only
way to consume essential vitamins
Antibiotics also kill good microbiota and excessive/unnecessary use has been associated with
risk factors for obesity, diabetes type 2 and autoimmune diseases.
Hygiene hypotheses: lack of early childhood exposure to all kinds of microbes, infectious
agents and parasites suppresses the natural development of the immune system.
1.3 How to study the Microbiome
Microscopy
o To understand cause of infectious diseases
Culturing
o You isolate a type of bacterium and grow it on a specific media to find out the
characteristics of the bacteria
Not all bacteria can be cultured yet is the right medium is unknown
o Also, to test if a bacterium is susceptible to certain antibiotic
Culture independent techniques: DNA, RNA, proteins or metabolites
o Finding out what they are capable of doing (in our bodies)
, Can give an idea about food digestion, vitamin production
o 16s rRNA gene: found in all bacteria and archaea but not in eukaryotes
Conserved/common region: to pinpoint the gene
Variable/specific part: identify species
1.3.2 Omics Approaches
Omics techniques: collective characterization and quantification of pools of biological
molecules: study millions of molecules in a snapshot
- Each analysis gives you a snapshot of the information/composition at a certain time
point of measurement.
- Generate big databases of molecular data form the microbiome
16S rRNA DNA profiling uses primers that amplify the 16S rRNA gene of all microbes
to create a database of DNA sequences
o Community profiling: determining the abundance of each kind of microbe,
community diversity
Microbes that are most abundant will be found back the most in the
sequence reads
o The sequence information will tell you:
Which DNA (and thus what microbes) is there
Which microbes are very well represented and which are present in
low numbers.
NOT the function
Metagenomics: Uses a set of primers that can amplify any gene of any
microorganism
o To study the genetic potential of the microbiome we can use the information
of the complete genomes of all microbes in a fecal sample
o Advantages
Reads can be grouped in batches, depending on what information you
are interested in
The genes can be used to assemble genomes and extrapolate
complete genomes from your fecal sample or discover complete
genomes of bacteria that are not yet cultured.
The genome information can be used to understand the needs of the
microbe and can help design a culture media for an uncultured
microbiota member
Compare the complete set of genes of the microbiome between
groups of individuals: helps to understand to actual functional
involvement of the microbiome in states of disease
The creation of big databases of microbial products through the sequencing can be
done for DNA, RNA, proteins and metabolites.
Each of these different approaches will give you clues about the function of the
microbiota.
, o It will also tell you what is most abundant, and if there are differences
between samples.
Note: generated results are only snapshots of a certain sample point, and the amount of
data needs to be taken into account to understand if the complete microbial community is
represented
Shotgun sequencing describes the gene content; the long stretch of the nucleotides adenine
(A), cytosine (C), guanine (G) and thymine (T).
1.4 Microbiota for Health
1.4.1 Microbiome Research and Causality
Causality: A influences B, the relationship between a cause and an effect
Correlation: A and B show a linear relationship
Association: connection between two factors, however it is possible that we miss other
factors that are involved.
The main challenge is to figure out the changes in the gut microbiome actually play a
role in disease.
o When a causative link has been proved, we might be able to modulate the gut
microbiota to diagnose, prevent or cure diseases
Example: A fecal microbiota transplant of a healthy gut microbiome composition can restore
the balance and get rid of the Clostridium difficile.
Approaches to find causative relationships between the gut microbiome and health:
Germ-free mice: mice that were never in contact with microbes
o Exposing these mice to micro-organisms, we can test the effect of the specific
bacteria on e.g. metabolism, digestion or immune response
o Don’t give us a decisive answer on the effectivity of a potential treatment in
which we influence the gut microbiome clinical trials needed
