Host-microbe interactions
Lecture 1
9/11
Introduction
- Functional significance of microorganisms colonizing our bodies
- 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 habitats
of the body
o Microbiota colonizing the skin is different from that of the gut
- Microbes found in all surfaces of the body, but majority present in the gut
Structure and function of the healthy adult human microbiome
- 10^12 cells → 10^4 genes
- 10^14 bacteria (+archaea, fungi and virsuses) → 10^6 genes
➔ Together: superorganism
o Processing of nutrients
o Degradation of xenobiotics
o Protection from new microbes
o Regulation of epithelial homeostasis
➔ Optimal fitness
Why 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
How to identify the gut microbiota
- Culturing → no
o Majority of microorganisms can not be cultured or enumerated using growth-
dependent approaches
- 16S ribosomal RNA: fingerprint
o Gene only in bacteria
- Fluorescent in situ hybridization
Fusion of culture and molecular-based analysis
- 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
metagenomic sequencing, which provides insights into the nutritional requirements of the
uncultured microorganisms
Overview of the human microbiome
- There are currently integrated projects underway to answer basic questions about the
human microbiome
o Do individuals share a core human microbiome?
▪ Yes
o Is there a correlation between the composition of microbiota colonizing a body site
and host genotype?
1
, ▪ Partly
▪ Environmental factors: food, pH, antibiotics, sanitation
o Do differences in the human microbiome correlate with differences in human
health?
▪ Yes
o Are differences in the relative abundance of specific bacterial populations important
to either health or disease?
▪ Yes
Major microbial populations in the body sites sampled by human microbiome projects
- Gastrointestinal tract
o Bacteroidetes
o Firmicutes
o → contribute the most
- Urogenital tract
o Lactobacillus
- Saliva
o Streptococcus
o Others
o Aerobic mostly
- Skin
o Propionibacterium
Oral cavity and airways
- The oral cavity is a complex, heterogeneous microbial habitat
- 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
- Respiratory tract
o Microbes thrive in the upper respiratory tract from the air during breathing
▪ Bacteria continually enter upper respiratory tract form 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
o Lower respiratory tract has no normal microbiota in healthy adults
▪ Ciliated mucosal cells move particles up and out of the lungs
Gastrointestinal microbiota
- Humans are monogastric and omnivorous
- Microbes in the gut affect early development, health, and predisposition to disease
- Colonization of gut begins at birth
Gastrointestinal tract: stomach → small intestine → large intestine
- Low number of microbes in stomach because low pH
- Increase of number of microbes in small intestine
- Phili in small intestine: increase area of absorption, main site of nutrient absorption
- High flow in small intestine → microbes washed away from small intestine
- Colon: absorption of water
o Crypts: phili in colon
o Product of digestion of carbohydrates: fatty acids
▪ Butarate: main source for colonocytes
2
, o Epithelial cells
▪ Goblet cells: produce mucus, slimy layer that covers epithelial layer,
translocation of bacteria form lumen to inner site
▪ enterocytes
▪ Paneth cells, only in small intestine
▪ Enteroendocrine cells: produce gut hormones → hunger and satiety
Gastrointestinal microbiota
- The 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 form 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 Heliobacter pylori was discovered in the 1980s and has since been found in 50% 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 form the digestion of food
o Most organisms are restricted to the lumen of the large intestine, while others are in
the mucosal layers
o Different microenvironments in the large
intestine
▪ The inner mucin layer, produced by
and contracting the gut mucosa, is
partly oxygenated but generally
free of bacteria. The sparsely
populated outer mucus layer is
adjacent to the heavily colonized
anoxic lumen, which receives
undigested food particles form the
small intestine
▪ Most nutrients absorbed in the
small intestine → to colon: fermenter, start breaking down molecules into
small molecules → nutrients receive the blood and brain → parts that will
not be absorbed, will be secreted
▪ More aerobic bacteria in small intestine, because closer to oral cavity
• Only will survive in upper part
- The vast majority (98%) of all human gut phylotypes fall into one of three major bacterial
phyla: firmicutes, Bacteroidetes, and proteobacteria
o Individuals may have mostly firmicutes, mostly Bacteroidetes, or a mix of the two.
This may regulate metabolism and the host’s propensity for obesity
3
, Urogenital tracts and their microbes
- Altered conditions can cause potential pathogens in the urethra (e. coli and proteus
mirabilis) to multiply and cause urinary tract infections
- The vagina of the adult female is weakly acidic and contains significant amounts of glycogen
- Lactobacillus acidophilus: resident organism in the vagina, ferments the glycogen, producing
lactic acid
- Lactic acid maintains a local acidic environment
- More diverse bacteria, better
The skin and its microbes
- There are approximately 1 million resident bacteria per square centimeter of skin for a total
of about 10^10 kin microorganisms covering the average adult
- The skin surface varies greatly in chemical composition and moisture content
- Three microenvironments
o Dry skin
o Moist skin
o Sebaceous skin (oily)
- Composition is influenced by
o Environmental factors (weather)
o Host factors (age, personal hygiene)
o Each environment shows a unique microbiota
4
Lecture 1
9/11
Introduction
- Functional significance of microorganisms colonizing our bodies
- 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 habitats
of the body
o Microbiota colonizing the skin is different from that of the gut
- Microbes found in all surfaces of the body, but majority present in the gut
Structure and function of the healthy adult human microbiome
- 10^12 cells → 10^4 genes
- 10^14 bacteria (+archaea, fungi and virsuses) → 10^6 genes
➔ Together: superorganism
o Processing of nutrients
o Degradation of xenobiotics
o Protection from new microbes
o Regulation of epithelial homeostasis
➔ Optimal fitness
Why 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
How to identify the gut microbiota
- Culturing → no
o Majority of microorganisms can not be cultured or enumerated using growth-
dependent approaches
- 16S ribosomal RNA: fingerprint
o Gene only in bacteria
- Fluorescent in situ hybridization
Fusion of culture and molecular-based analysis
- 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
metagenomic sequencing, which provides insights into the nutritional requirements of the
uncultured microorganisms
Overview of the human microbiome
- There are currently integrated projects underway to answer basic questions about the
human microbiome
o Do individuals share a core human microbiome?
▪ Yes
o Is there a correlation between the composition of microbiota colonizing a body site
and host genotype?
1
, ▪ Partly
▪ Environmental factors: food, pH, antibiotics, sanitation
o Do differences in the human microbiome correlate with differences in human
health?
▪ Yes
o Are differences in the relative abundance of specific bacterial populations important
to either health or disease?
▪ Yes
Major microbial populations in the body sites sampled by human microbiome projects
- Gastrointestinal tract
o Bacteroidetes
o Firmicutes
o → contribute the most
- Urogenital tract
o Lactobacillus
- Saliva
o Streptococcus
o Others
o Aerobic mostly
- Skin
o Propionibacterium
Oral cavity and airways
- The oral cavity is a complex, heterogeneous microbial habitat
- 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
- Respiratory tract
o Microbes thrive in the upper respiratory tract from the air during breathing
▪ Bacteria continually enter upper respiratory tract form 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
o Lower respiratory tract has no normal microbiota in healthy adults
▪ Ciliated mucosal cells move particles up and out of the lungs
Gastrointestinal microbiota
- Humans are monogastric and omnivorous
- Microbes in the gut affect early development, health, and predisposition to disease
- Colonization of gut begins at birth
Gastrointestinal tract: stomach → small intestine → large intestine
- Low number of microbes in stomach because low pH
- Increase of number of microbes in small intestine
- Phili in small intestine: increase area of absorption, main site of nutrient absorption
- High flow in small intestine → microbes washed away from small intestine
- Colon: absorption of water
o Crypts: phili in colon
o Product of digestion of carbohydrates: fatty acids
▪ Butarate: main source for colonocytes
2
, o Epithelial cells
▪ Goblet cells: produce mucus, slimy layer that covers epithelial layer,
translocation of bacteria form lumen to inner site
▪ enterocytes
▪ Paneth cells, only in small intestine
▪ Enteroendocrine cells: produce gut hormones → hunger and satiety
Gastrointestinal microbiota
- The 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 form 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 Heliobacter pylori was discovered in the 1980s and has since been found in 50% 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 form the digestion of food
o Most organisms are restricted to the lumen of the large intestine, while others are in
the mucosal layers
o Different microenvironments in the large
intestine
▪ The inner mucin layer, produced by
and contracting the gut mucosa, is
partly oxygenated but generally
free of bacteria. The sparsely
populated outer mucus layer is
adjacent to the heavily colonized
anoxic lumen, which receives
undigested food particles form the
small intestine
▪ Most nutrients absorbed in the
small intestine → to colon: fermenter, start breaking down molecules into
small molecules → nutrients receive the blood and brain → parts that will
not be absorbed, will be secreted
▪ More aerobic bacteria in small intestine, because closer to oral cavity
• Only will survive in upper part
- The vast majority (98%) of all human gut phylotypes fall into one of three major bacterial
phyla: firmicutes, Bacteroidetes, and proteobacteria
o Individuals may have mostly firmicutes, mostly Bacteroidetes, or a mix of the two.
This may regulate metabolism and the host’s propensity for obesity
3
, Urogenital tracts and their microbes
- Altered conditions can cause potential pathogens in the urethra (e. coli and proteus
mirabilis) to multiply and cause urinary tract infections
- The vagina of the adult female is weakly acidic and contains significant amounts of glycogen
- Lactobacillus acidophilus: resident organism in the vagina, ferments the glycogen, producing
lactic acid
- Lactic acid maintains a local acidic environment
- More diverse bacteria, better
The skin and its microbes
- There are approximately 1 million resident bacteria per square centimeter of skin for a total
of about 10^10 kin microorganisms covering the average adult
- The skin surface varies greatly in chemical composition and moisture content
- Three microenvironments
o Dry skin
o Moist skin
o Sebaceous skin (oily)
- Composition is influenced by
o Environmental factors (weather)
o Host factors (age, personal hygiene)
o Each environment shows a unique microbiota
4
