Notes of all the lectures given in the host microbe interactions course. Mostly everything that was said was written down, some parts just the information on the slides.
HOST-MICROBE INTERACTIONS
LECTURE 1. MICROBIAL SYMBIOSES WITH HUMANS
Chapter 24. Sahar El Aidy
There is a functional significance of microorganisms colonizing our bodies. They are 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 colonize different habits of the body.
Microbiota colonizing the skin is different from that of the
gut.
In the early 19s it was really hard to perform a surgery in a sterile surround without the patient getting
an infection after. In Notredame in France the first sterile surgery was performed. This brought the
question; How long could men live in a germless world?. People started using a lot of disinfections and
thereby the number of microbiota which were important for our health.
Why is it important to know the human microbiota?
• Development of biomarkers to predict predisposition to specific diseases
• Design of therapies targeting selected microbial species in particular body sites
• Personalized diet/drug therapies
• Tailor-made probiotics
Culturing is not sufficient to tell which microbes we have in our body. The majority of microorganisms
in the gut cannot be cultured or enumerated using growth-dependent approaches. This is because we
do not have all the information about the nutrients, and it is too labor intensive. Also we can’t exactly
reproduce the environment that is in the human body. Instead we rely specifically in probiota on a
sort of fingerprint of them 16S ribosomal RNA to identify the gut microbiota.
,Fluorescent in situ hybridization or qPCR can be used to target genes in the bacteria so we can make
them fluorescent and they can be seen under a microscope. And with qPCR the absolute number can
be found.
Culturing is still very important, to see the interactions between bacteria and the physiology of the
microbe.
The focus on molecular sequences in microbiome studies does not diminish the importance of
cultivation in the study of the human microbiome. The development of appropriate culture conditions
for isolation is being guided by metagenomics sequencing, which provides insights into the nutrional
requirements of the uncultured microorganisms.
There are currently integrated projects underway to answer basic questions about the human
microbiome:
1. Do individuals share a core human microbiome? à Yes, apart from having millions of these
microbes in our body, we share core microbes with all human beings. Individuals become
different on the species level and the strain level
2. Is there a correlation between the composition of microbiota colonizing a body site and host
genotype? à Yes, the genetics of the host indeed has an effect on which microbes colonize.
However, if we look in the environmental factors, they have a larger effect on the type of
microbes. Examples of these factors are: food/diet, acidity, birth, antibiotics, sanitation.
3. Do differences in the human microbiome correlate with differences in human health? à Yes
4. Are differences in the relative abundance of specific bacterial populations important to either
health of disease? à Yes they are. Will be explored in the coming lectures.
Things you need to know from the picture above
are the main contributors in the specific place in
the body.
• Gastrointestinal tract: Bacteroidetes,
Firmicutes
• Urogenital tract: Lactobacillus
• Saliva: Streptococcus (more aerobic
bacteria, with the 16S RNA also anaerobic
bacteria are found)
• Skin: Propionibacterium
The oral cavity is a complex heterogeneous microbial habitat. The
saliva contains antimicrobial enzymes. High concentrations of
nutrients near surfaces in the mouth promote localized microbial
growth. The tooth consists of a mineral matrix (enamel)
surrounding living tissue, the dentin and pulp.
,In the respiratory tract microbes are mainly in the upper respiratory tract. The bacteria continually
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. Ciliated mucosal cells move
particles up and out of the lungs.
Humans are monogastric and omnivorous, microbes in the gut affect early development, health and
predisposition to disease. Colonization of gut begins at birth.
In the gastrointestinal tract the stomach is usually neglected when
talking about microbes because the pH of the stomach is very low.
Which does not allow microbes to be there. As we go down in the small
intestine the pH increases. A major difference between the small
intestine and large intestine is the villi, those increase the surface in
the small intestine. In the small intestine the number of microbes is
lower than in the large intestine. This is because of the transit time, in
the small intestine the flow is still very high, microbes can’t stay in
place and will be flushed away.
Four different types of epithelial cells are: Introsides, goblet cells (produce mucus), paned cells (only
in small intestine) & enteroendocrine cells (produce satiety hormones).
Gastrointestinal microbiota:
• Stomach and small intestine
o Microbial populations in different areas of the GI tract are influenced by diet and the
physical conditions in the area
o The acidity of the stomach (pH 2) prevents many organisms from colonizing the GI
tract; however, there is a rich microbiome in the healthy stomach.
o Firmicutes, Bacteroidetes and Actinobacteria are common in the gastric fluid, while
firmicutes and proteobacteria are common in the mucus layer of the stomach.
o Helicobacter pylori was discovered in the 1980s and has since been found in ±50
percent of the world’s population. When present, it is found in the gastric mucosa
Intestinal microorganisms carry out a variety of essential metabolic reactions that produce various
compounds
• The large intestine
o The colon is essentially an in vivo fermentation vessel, with the microbiota using
nutrients derived from the digestion of food.
o Most organisms are restricted to the lumen of the large intestine, while others are in
the mucosal layers (figure 24.6)
, From the small intestine, where most nutrients are absorbed
the food will go to the colon. The colon is the main bioreactor
or fermenter. It will produce short chain fatty acids that can
go into the blood stream. Finally, the parts that cannot be
taken up by the bacteria are excreted.
Major members of the microbiota in the gut are:
In the small intestine there are more
aerobic bacteria because there is more
oxygen present.
The vast majority (98 percent) of all
human gut phylotypes fall into one of
three major bacterial phyla: Firmicutes,
Bacteroidetes and Proteobacteria.
Individuals may have mostly Firmicutes,
mostly Bacteroidetes or a mix of the two.
This may regulate metabolism and the
host’s propensity for obesity
Urogenital tracts and their microbes. Altered conditions can cause potential pathogens in the urethra
(e.g. E.coli and Proteus mirabilis) to multiply and cause urinary tract infections.
• Vagina of the adult female is weakly acidic and contains significant amounts of glycogen
• Lactobacillus acidophilus, a resident organism in the vagina, ferments the glycogen, producing
lactic acid.
• Lactic acid maintains a local acidic environment
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