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Summary Host-Microbe Interactions
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Host-microbe interactionsLecture 1 – introducti on Chapter 24 S.EI Aidy
Are we one or are we many
- 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 habits of
the body. Microbiota colonizing the skin is different from that of the gut.
Figure 24.1 represent the microbial habitats of the human body.
Structure and Function of the healthy adult human microbiome
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.
How to identify the gut Microbiota?
- Maybe by culturing? Not all microbes can be cultured
due to the lack of information about nutrient
requirements or other factors.
- Majority of microorganisms can’t be cultured or
enumerated using growth-dependent approaches.
Fusion of culture and molecular-based analyses
- 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.
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,Overview of the Human Microbiome
There are currently integrated projects underway to answer basic questions about the human
microbiome:
1. All humans share a core human microbiome.
2. Is there a correlation between the composition of microbiota colonizing a body site and host
genotype?
3. Differences in the human microbiome correlate with differences in human health (diseases).
4. Are differences in the relative abundance of specific bacterial populations important to either
health or disease?
Fig. 24.2; major microbial populations in the body sites sampled by human microbiome projects.
(in the skin (Propionibacterium and staphylococcus) in the salvia (others and streptococcus) in the
urogenital tract (lactobacillus) and in the gastrointestinal tract (Bacteroidetes and firmicutes).
Fig. 24.7; bacterial diversity of salvia, most bacteria are aerobic.
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 (know the names)
Microbes thrive in the upper respiratory tract.
- Bacteria continually enter 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.
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.
- Fig. 24.4; microbiota in the small intestine.
- Intestinal microorganisms carry out a variety of essential
metabolic reactions that produce various compounds.
The Stomach and Small Intestine
- Microbial populations in different areas of the GI tract are influenced by diet and the physical
conditions in the area.
- 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.
- Firmicutes, Bacteroidetes, and Actinobacteria are common in the gastric fluid, while
Firmicutes and Proteobacteria are common in the mucus layer of the stomach.
- 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.
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,The Large Intestine (Bacteroidetes and Firmicutes) Fig. 24.5
- The is essentially an in vivo fermentation vessel, with the microbiota using nutrients derived
from the digestion of food.
- Most organisms are restricted to the lumen of the large intestine, while others are in the
mucosal layers. (Figure 24.6).
- Major members of the microbiota in the gut shown in figure 24.3 (need to know the main
bacteria). In the small intestine you find more aerobic (closer to respiratory tract) bacteria.
The major difference between the small and large intestine is the Villi in the small intestine, these
Villi is used for increasing the surface area. The large intestine (colon) doesn’t absorb nutrients only
water so it only have Crypts.
Types of epithelial cells: slide 17
1. Enterocyte cell; this constitute the majority of the epithelial cells, this are the secretory cells.
2. Goblet cells; produce mucus, the slightly layer that covers the epithelial layer, avoid the
translocation of bacteria from the lumen to the inner side of the lamina propria.
3. Paneth cells; in the small intestine crypts, provide the host with anti-microbe peptide.
4. Enteroendocrine cells; producing gut hormones, for satiety and hunger.
Gastrointestinal Microbiota, Table 24.2
- 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 Bacteriodetes, 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. Escherichia
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, a resident organism in the vagina, ferments the glycogen,
producing lactic acid.
- Lactic acid maintains a local acidic environment.
- Vaginal bacterial diversity shown in Figure 24.12 (Firmicutes).
The Skin and Its Microbes
- There are approximately 1 million resident bacteria per square centimeter of skin for a total
of about 1010 skin microorganisms covering the average adult.
- The skin surface varies greatly in chemical composition and moisture content
- three microenvironments:
dry skin
moist skin
sebaceous skin (oily)
Composition is influenced by;
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, - environmental factors (e.g., weather)
- host factors (e.g., age, personal hygiene).
- Each microenvironment shows a unique microbiota.
Fig. 24.14; Skin bacterial diversity at the inside of the elbow (need to know actinobacteria).
Minute 44.
Human Study Groups and Animal Models
Human Microbiome Study Groups have formed most of our understanding of the functions of the
human microbiome.
- 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.
Mouse Models (slide 34)
While there are significant differences between mice and humans, mice have been used to study
human gut microbiome interactions.
- Mice have a larger cecum than humans.
- Most fermentation is completed in the mouse cecum, rather than the human large intestine.
Mice have a short life cycle and well-defined genetic lines; they can be raised in a germ-free
environment.
- antibiotic therapy
- strict dietary control
- fecal transplants
- germ-free environment
Colonization, Succession, and Stability of the Gut Microbiota
Microbial Activities in the First Year of Life
- Colonization begins at birth, with transfer from mother to infant.
- Early colonizing microbes are a source of vitamins and amino acids and tend to be facultative
rather than obligate anaerobes.
Variables determine the nature of the gut microbiome.
- Vaginally born infants have a microbiome more similar to that of their mothers than those
born via Cesarean section.
- Breastfed infants have more of a certain type of commensal bacteria (Bifidobacteria), as
breast milk has oligosaccharides that promote their colonization. (Figure 24.17). Most gut
microbes and humans are unable to digest these oligosaccharides.
- Formula infants has less of a certain type of commensal bacteria.
Stability of the Adult Microbiome and Transitions with Age
- Early experiences determine gut microbiome.
- Aging and frailty are associated with decreased microbial diversity.
Disorders Attributed to the Gut Microbiota
The Role of the Gut Microbiota in Obesity: Mouse
Models
- Normal mice have 40 percent more fat than
germfree mice with the same diet. When germ-
free mice were given normal mouse
microbiota, they started gaining weight.
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