Summary consists of:
1. Introduction to microbiome; oral, skin, and gut (composition and function). (El Aidy)
2. Metagenomic (pathway analysis) and Multi-omics bio-bank cohort analysis (Harmsen)
3. Early live microbiome (Harmsen + El Aidy)
4. Diet and Lifestyle and microbiome (El Aidy)
5. Sma...
Human microbiota: types of organisms present in an environmental habitat.
Human microbiome: genome collection of microbes in a particular environmental system, which
refer to their function.
- The human microbiome is comprised of different microbiota that colonise different habitats
of the body. The microbiota in the skin is different from the gut.
- Commensal microbes (archaea, bacteria, viruses) are present in a greater amount than
somatic cells in the human body.
- The function of human microbiome is to process nutrients, degrade xenobiotics, protection
from new microbes or regulation of epithelial homeostasis. All together they provide optimal
fitness for the host.
Culturing of microbiota only works in 30% of cases, because it is not known which growth-dependent
approach is required for each specific microorganism. Moreover, the presence of oxygen kills many
microbes. Sequencing is a better approach, using 16S ribosomal RNA, only present in the RNA of
bacteria. But microbiome also contains viruses and archaea which cannot be targeted with this
experiment.
o Still, culturing is still of importance for studying the function, structure of bacteria
and its proteins.
Basic questions about the human microbiome:
1. Do individuals share a core human microbiome?
2. Is there a correlation between the composition of microbiota colonizing a body site and host
genotype?
3. Do differences in the human microbiome correlate with differences in human health?
4. Are differences in the relative abundance of specific bacterial populations important to either
health or disease?
- The natural habitat of certain microbes is different, for some the skin, for some the gut. If the
relative abundance of a gut-microbe increases in the skin, this can result in a dermatological
disease.
,Human and Microbes
ORAL CAVITY
Bacterial diversity of saliva: the composition of the saliva consists of the proteobacteria, firmicutes
(streptococcus) and Bacteroidetes (prevotellacae)
o Consists of antimicrobial enzymes
o High concentrations of nutrients in the mouth promote the growth of nutrients
o The tooth consists of a mineral matrix (enamel) surrounding living tissue, the dentin,
and pulp.
RESPIRATORY TRACT
- Microbes live in the upper respiratory tract. Bacteria continuously enter the
upper respiratory tract from the air during breathing. Most are trapped in the
mucus of the nasal and oral passages and expelled with nasal secretions or
swallowed and then killed in the stomach.
- The lower respiratory tract has no normal microbiota in healthy adults. The
ciliated musical cells move particles up and out of the lungs.
GASTROINTESTINAL
Microbial populations in different areas of the gastrointestinal tract are influenced by diet and
physical conditions of the area. The pH gradually increased as it goes from the stomach (pH = 2) to
the small intestine and eventually the large intestine.
Humans are monogastric (one stomach) and omnivorous (eating meat)
Most organisms are restricted to the lumen of the large intestine, while others are in the mucosal
layers.
,The vast majority of all human gut phylotypes fall into one of the three major bacterial phyla:
1. Firmicutes
2. Bacteroidetes
- The most abundant family in the colon within the phylum Bacteroides is Bacteroidaceae
3. Proteobacteria
The ratio may differ in individuals and this may regulate metabolism and the host’s propensity for
obesity.
STOMACH
Its overall function is to secrete acid (HCl) and digest macromolecules.
- The acidity of the stomach prevents many organisms from colonizing the stomach.
- Overall, Firmicutes and Proteobacteria are mainly present in the mucus layer of the stomach,
while Firmicutes, Bacteroidetes and Actinobacteria are common in the gastric fluid.
- Helicobacter pylori is found in the gastric mucosa and is related to gastric cancer.
SMALL INTESTINE
The small intestine is important in absorbance of nutrients – containing villi to increase surface.
Epithelial layer is the first layer that microbiota come in touch with.
The next layer is the lamina propria (contains immune cells involved in innate immunity)
Next is the enteric nervous system layer.
LARGE INTESTINE
- Highest number of microorganisms; mainly Bacteroidetes and Firmicutes. They dominate the
normal microbiota of the large intestine. There are different microenvironments in the large
intestine.
- The large intestine does not have villi, it is mainly important in absorbing water.
- The colon is essentially an in vivo fermentation vessel, with the microbiota using nutrients
derived from the digestion of food.
Most bacteria live in the lumen (fluid). Others live in the mucosa that cover
the epithelial cells, the mucus layer is very rich in nutrients. The mucus layer
is much thicker in the large intestine than in the small intestine, that is why
there are more bacteria in the mucus layer of the large intestine.
- From the small intestine, the undigested food particles
(polysaccharides) enter the large intestines. The large intestine
therefore contains a lot of enzymes that can break down these
polysaccharides. The parts that are still not digested after this, will go
to the anus.
UROGENITAL TRACT
- Least variation in microbes – mainly lactobacillus, a member of the Firmicutes family.
- Lactobacillus ferments glycogen, producing lactic acid that maintains an acid environment in
the vagina.
- Altered conditions can cause potential pathogens in the urethra (e.g. E.Coli) to multiply and
cause urinary tract infections.
THE SKIN
Three microenvironments
- Dry skin
- Moist skin
, - Sebaceous skin (oily)
The composition is influenced by environmental factors (weather), host factors (age, hygiene) and
which microbiota are present.
Most bacteria in the skin are aerobic.
Study microbiome
- HMS - The Human Microbiome Project (HMP) surveyed hundreds of medical students over
several years to determine a baseline for healthy human microbiomes. Later projects showed
the weakness in this model, as they revealed more diversity in non-US born subjects and
lacked data on diet or other lifestyle attributes.
o The results from the Human Microbiome Project are limited because of the lack of
geographical diversity.
- Mouse models – they have a much larger cecum, because most fermentation processes take
place in the cecum, whilst in humans this occurs in the large intestine. In terms of genetics,
mice are good used models, they have a short life-cycle and are well-defined in genes. They
can be raised in a germ-free environment.
Early Development
Colonization of microbes begins at birth, with transfer from mother to the child. Early colonizing
microbes are a source of vitamins and tend to be facultative rather than obligate anaerobes.
Microbes in the gut affect early development health and plays a major role in predisposing diseases.
o Vaginally born infants have a microbiome more similar to that of their mothers than
those born via Caesarean section.
o Breast-fed infants have more of a certain type of commensal bacteria
(Bifidobacteria), as breast milk has oligosaccharides that promote their colonization.
Disorders attributed to microbiota
OBESE
Hypothesis 1:
- Normal mice have 40 percent more fat than germfree(no microbes) mice with the same diet.
When germ-free mice were given normal mouse microbiota, they started gaining weight.
Mice that are genetically obese have different microbiota than normal mice. Obese mice
have more Firmicutes.
As said,
The vast majority of all human gut phylotypes fall into one of the three major bacterial phyla:
1. Firmicutes
2. Bacteroidetes
3. Proteobacteria
The ratio may differ in individuals and this may regulate metabolism and the host’s propensity for
obesity. So, people having more Firmicutes have a higher chance of obesity.
Hypothesis 2:
Normally, food is fermented to nutrients (for the host) and to H 2 by microbes. A high level H2
indicates that there is enough food intake, so the fermentation process is blocked.
- In obese: methanogens convert H2 CH4, so there are no high levels of H2 and fermentation
will not be blocked. So obese people have high levels of fermentation.
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