The Microbiota

Question 1

What is the microbiota?

Answer 1

The human body is an ideal habitat for many bacteria and other microorganisms.

The body’s internal tissues, such as blood, brain, muscle, are normally sterile.

The surface tissues such as the skin and mucous membranes (a good example is our whole digestive tube: from the mouth through the intestines and out the other end) are constantly in contact with microorganisms present in the environment.

These areas of the body are a series of microenvironments and are colonized by certain microbial species.

In general, the same bacterial species colonize the same anatomical sites in all people and are referred to the microbiota.

Some organisms establish permanent residence within the host while others are more transient and are present for limited periods of time (days, weeks, months).

Question 2

What benefit do bacteria obtain from the host?

Answer 2

• supply of nutrients
• stable environment (i.e., protection from desiccation, temperature extremes)
• mode of transport

Question 3

What benefit does the host gain from bacteria?

Answer 3

• microbial antagonism whereby the microbiota inhibits colonization by pathogens
• certain nutritional synergisms
• stimulation of the immune system

Question 4

How does the microbiota inhibit colonization by pathogens?

Answer 4

• occupies adherence sites
• utilizes nutrients
• produces inhibitory by-products
• affects conditions such as pH and available oxygen

Question 5

Describe nutritional benefits humans derive from their gut microbiota.

Answer 5

• synthesis and excretion of vitamins in excess of their own needs, which can be absorbed as nutrients by the host (e.g., vitamin K, vitamin B12)
• steroid metabolism (e.g., bile acids are converted to steroids that are reabsorbed by the host)
• organic acid production (e.g., acetic acid, butyric acid)
• glycosidase reactions (e.g., sugar fermentations)

Question 6

Describe why stimulation of the immune system by the microbiota is a good thing.

Answer 6

The microbiota can induce an antibody response in the host, and the low levels of antibodies produced against components of the microbiota (sometimes called ‘natural antibodies’) can cross react with certain related pathogens, and thereby prevent infection or invasion.

Question 7

The microorganisms of the microbiota are adapted to their host.

Give examples of microbiota-host adaptation.

Answer 7

The physical association between the microbiota and the host most likely involve biochemical interactions between bacterial surface components (ligands or adhesins) and host cell molecular receptors.

Another example of microbiota-host adaptation is that although it is not well understood how the bacteria of the microbiota resist innate immune defences and do not elicit strong adaptive immune responses that would lead to their elimination, at least one study suggested that the induction of a phosphatase in intestinal epithelial cells by bacteria of the microbiota could then detoxify the microbiota’s LPS, rendering them less sensitive to the innate immune system.

Question 8

Give examples of harmful, or unwanted, aspects of the host-microbiota relationship.

Answer 8

• The pathogenic potential of the microbiota if introduced into other locations in the body: e.g., Escherichia coli, which is a normal resident in the gastrointestinal (GI) tract, may cause urinary tract infections when introduced into the urinary tract.
• The production of intestinal gas. Bacteria in the large intestine ferment food ingested by the host, giving rise to gaseous by-products. These gases include CO2, H2, NH3, and H2S. Methanogens convert the H2 and CO2 produced by other intestinal microorganisms to methane (CH4). Human intestinal microbiota are responsible for the production of approximately 300–400 ml gas per day.

Question 9

Describe host-microbiota interactions that may help or harm the host.

Answer 9

Recently, it has been shown that the intestinal microbiota also affect the brain.

This is called the gut-brain axis, and it is bidirectional: the brain acts on gastrointestinal and immune functions that help to shape the gut’s microbial makeup, while the gut microbes in turn affect inflammatory responses that act on the brain and also make neuroactive compounds, including neurotransmitters and metabolites, that then act on the brain.

This can have positive or negative effects on many brain functions and disorders, including, for example, development or prevention of anxiety and Multiple Sclerosis.

It is now known that the balance of microbiota also likely contribute to the development or prevention of colorectal cancer.

This is a complex phenomenon involving many components including both host factors and environmental sources (i.e., diet, antibiotic use) and is an area of significant current investigation.

Question 10

The fetal environment is sterile, and prior to birth, humans are free of microorganisms.

How is the microbiota obtained?

Answer 10

The microbiota is obtained from the environment immediately after birth as a result of:

• passage through the birth canal
• exposure to other humans (and pets)
• ingestion of food and fluids
• inhalation of air-borne microorganisms

Question 11

How quickly are bacterial colonizers acquired after birth?

Answer 11

These bacterial colonizers are acquired quickly.

For example:

• mouth cultures are positive 6 hours after birth
• fecal cultures are positive 10–20 hours after birth

Question 12

What factors affect the composition of the microbiota?

Answer 12

• diet – an infant’s diet of milk encourages the establishment of lactic acid bacteria as part of the microbiota
• infection – which results in a temporary increase in pathogen numbers
• oral antibiotic therapy – which may result in a decrease in the microbiota of the GI tract leaving the way open for opportunistic bacteria to colonize (e.g., the overgrowth of Clostridium difficile may cause colitis. Colitis is an inflammatory disease of the colon). After the antibiotic therapy is completed, the microbiota eventually re-establishes itself.

Question 13

What are three explanations for why the bacteria of the microbiota are located at a particular anatomical site?

Answer 13

1. The host provides an essential growth factor needed by the bacterium. Alternatively, some locations of the host are inherently inhospitable for the colonization of bacteria (i.e., due to the production of stomach acids, bile salts and lysozyme).
2. At colonization sites, the bacteria attach to the host receptors using specific bacterial ligands (e.g., capsules, cell wall components, fimbriae). The host receptors that interact with the bacterial ligands are expressed only at certain locations in the host’s body.
3. Some members of the microbiota are able to construct bacterial biofilms on a surface of a tissue (or implants such as catheters). Other members of the microbiota may then establish themselves as part of a biofilm built by another bacterial species. Many biofilms are a mixture of microorganisms, although one member may predominate in the biofilm.

Question 14

What factors may affect the microbiota of the skin?

Answer 14

• weather – this may change the temperature and moisture content of the skin
• age – young children tend to have a more varied microbiota
• personal hygiene
• diet.

Question 15

How does the skin surface vary?

Answer 15

Chemical composition and moisture content, the density and composition of the microbiota of the skin varies with anatomical locale.

Question 16

Where are most skin organisms associated directly or indirectly?

Answer 16

Most skin microorganisms are associated directly or indirectly with sweat glands.

The warmth and high moisture content of the armpit, genital region, and areas between the toes supports the activity and growth of relatively high densities of bacterial cells, while the density of bacterial populations on smooth, dry skin is generally low.

Question 17

Why does the upper region of the hair follicles provide an ideal habitat for many microorganisms?

Answer 17

The secretions of the sebaceous gland associated with the hair follicle contain microbial nutrients such as urea, amino acids, salts, lactic acid and lipids.

Question 18

Why is saliva not a good culture medium?

Answer 18

It contains few nutrients and contains antibacterial substances such as lysozyme and lactoperoxidase.

Lysozyme weakens bacterial cell walls by cleaving the glycosidic linkages in the peptidoglycan.

Lactoperoxidase kills bacteria in a reaction that generates singlet oxygen.

However, the presence of food particles and epithelial debris makes the mouth a favorable habitat for a great variety of bacteria.

Question 19

What is plaque and how is it formed?

Answer 19

Bacteria can grow on tooth surfaces in thick layers called plaque.

Plaque is a type of complex biofilm.

Dental plaque formation is initiated by the deposit of a thin organic film of acidic glycoproteins from the saliva.

This film is several micrometers thick, and provides an attachment and colonization site for a few species of Streptococcus.

The microorganisms in plaque produce adherent substances (glucans) that encourage further colonization.

The bacteria then multiply extensively to form a biofilm.

Question 20

What are dental caries?

Answer 20

The destruction of the enamel, dentin or cementum of teeth caused by acid-producing bacteria in plaque.

Lactic acid bacteria produce lactic acid from the fermentation of sugars and other carbohydrates in the diet of the host.

Streptococcus mutans has most consistently been associated with the initiation of dental caries, but other lactic acid bacteria are probably involved as well.

These organisms normally colonize the occlusal fissures and contact points between the teeth.

Question 21

What are periodontal diseases?

Answer 21

Bacterial infections that affect the supporting structures of the teeth (gingiva, cementum, periodontal membrane and alveolar bone).

The most common form, gingivitis, is an inflammatory condition of the gums.

Question 22

Where do the majority of microbiota in the human body reside?

Answer 22

Gastrointestinal (GI) tract.

Question 23

What does the GI tract consist of?

Answer 23

The GI tract consists of the stomach, small intestine and large intestine.

Question 24

What is the intestinal microbiota?

Answer 24

A complex ecosystem containing several hundred bacterial species in which the majority of these bacteria are anaerobes.

Some examples of anaerobic microorganisms include E. coli (a facultative anaerobe), Bacteroides (a strict anaerobe) and Lactobacillus (an aerotolerant anaerobe).

Question 25

Are there bacteria in the stomach?

Answer 25

The stomach is very acidic and is a barrier to most microbial growth.

The bacterial count of the stomach is usually very low and is considered to be devoid of any significant microbiota.

Only a few acid-tolerant bacteria can be cultured from the stomach.

For example, Helicobacter pylori are one of the few bacteria that can colonize the stomach wall.

This bacterium is the causative agent of gastric ulcers and gastric cancer, and infects over half the world’s population.

Question 26

Are there bacteria in the upper respiratory tract?

Answer 26

A large number of bacterial species colonize the upper respiratory tract (nasopharynx).

These microorganisms will colonize areas that are bathed with the secretions of the mucous membranes.

Bacteria enter the upper respiratory tract in air during breathing but are trapped in the nasal passages and expelled with the nasal secretions.

Question 27

Are there bacteria in the lower respiratory tract?

Answer 27

The lower respiratory tract is virtually free of microorganisms.

Dust particles which may carry microorganisms are fairly large and are trapped in the upper respiratory tract.

Furthermore, the lower respiratory tract is lined with ciliated epithelium.

Any bacteria reaching the lower respiratory tract are swept upward by the beating action of the cilia toward the upper respiratory tract where they are removed by subsequently by coughing, sneezing, swallowing (i.e., mucocilary action).

If the respiratory tract epithelium becomes damaged, as in bronchitis or viral pneumonia, the individual may become susceptible to infection by pathogens descending from the nasopharynx (e.g., Haemophilus influenzae or Streptococcus pneumoniae).

The pathogen Bordetella pertussis is specifically able to colonize the tracheal epithelium of humans, allowing it to produce the disease pertussis (whooping cough)

Question 28

Are there bacteria in the urogenital tract?

Answer 28

Urine is normally sterile, and since the urinary tract is flushed with urine every few hours, microorganisms have problems gaining access and becoming established.

Thus the urogenital tract is normally sterile with the exception of the vagina and the distal 1 cm of the urethra.

Lactobacillus sp. predominates in the vagina. These organisms generally lower the pH to around 4–5, which is optimal for the lactobacilli but inhibitory for the growth of many other bacteria.

Loss of this protective effect by antibiotic therapy can lead to infection by Candida (i.e., ‘yeast infection’).

The urethra may contain predominantly skin microorganisms including staphylococci, streptococci and diphtheroids.

Question 29

What are characteristics of gnotobiotic animals and birds?

Answer 29

• abnormal anatomical and physiological features
• underdeveloped lymphatic tissue and poorly developed immune systems
• thin intestinal wall
• low antibody titer
• higher susceptibility to pathogens
• reduced susceptibility to certain disease processes which are dependent on the activity of microbes (e.g., dental caries).

Scientists are still learning about the effects of an animal being gnotobiotic on brain function, but have already transplanted different species of gut bacteria to gnotobiotic bacteria and seen behavioural changes.

Question 30

What is a gnotobiotic animal?

Answer 30

Gnotobiotic literally means ‘known life’ but is typically used to mean germ free.

Question 31

How can gnotobiotic animals and birds be used to study the importance of the normal microbiota?

Answer 31

Colonies of gnotobiotic animals and birds are established by isolating the first generation offspring using sterile techniques.

These offspring are then raised in germ-free environments.

For mammals, this involves delivering the offspring by cesarean section.

For birds, this means that the exterior surface of the egg is sterilized.

Once the first generation has been established, they can be maintained and bred in germfree environments.