Why is it called the normal flora?

The term flora is used for the collective bacteria and other microorganisms in an ecosystem such as the human host. It has been estimated that humans have approximately 10¹³ cells in the body and something like 10¹⁴ bacteria associated with them, the majority in the large bowel. Members of groups such as viruses, fungi and protozoa are also regularly found in healthy individuals, but form only a minor component of the total population of resident organisms.

The organisms occur in those parts of the body that are exposed to, or communicate with, the external environment, namely the skin, nose and mouth and intestinal and urinogenital tracts. The main organisms found in these sites are shown in Figure 8.1. Internal organs and tissues are normally sterile.

Figure 8.1 Examples of organisms that occur as members of the normal flora and their location on the body.

(*Those found in the intestine are detailed in Fig. 8.2.)

The normal flora is acquired rapidly during and shortly after birth and changes continuously throughout life

The organisms present at any given time reflect the age, nutrition and environment of the individual. It is therefore difficult to define the normal flora very precisely because it is to a large extent environmentally determined. This is well illustrated by data from NASA astronauts who were rendered relatively bacteriologically sterile by antibiotic treatment before their space flights. It took only 6    weeks after the flight for their flora to re-populate, and the re-populating species were precisely those of their immediate neighbours. The bowel flora of children in developing countries is quite different from that of children in developed countries. In addition, breast-fed infants have lactic acid streptococci and lactobacilli in their gastrointestinal tract, whereas bottle-fed children show a much greater variety of organisms.

Different regions of the skin support different flora

Exposed dry areas are not a good environment for bacteria and consequently have relatively few resident organisms on the surface, whereas moister areas (axillae, perineum, between the toes, scalp) support much larger populations. Staphylococcus epidermidis is one of the commonest species, making up some 90% of the aerobes and occurring in densities of 10³–10⁴/cm²; Staphylococcus aureus may be present in the moister regions.

Anaerobic diphtheroids occur below the skin surface in hair follicles, sweat and sebaceous glands, Propionibacterium acnes being a familiar example. Changes in the skin occurring during puberty often lead to increased numbers of this species, which can be associated with acne.

A number of fungi, including Candida, occur on the scalp and around the nails. They are infrequent on dry skin, but can cause infection in moist skinfolds (intertrigo).

Both the nose and mouth can be heavily colonized by bacteria

The majority of bacteria here are anaerobes. Common species colonizing these areas include streptococci, staphylococci, diphtheroids and Gram-negative cocci. Some of the aerobic bacteria found in healthy individuals are potentially pathogenic (e.g. Staph. aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Neisseria meningitidis); Candida is also a potential pathogen.

The mucous membranes of the mouth can have the same microbial density as the large intestine, numbers approaching 10¹¹/g wet weight of tissue.

Dental caries is one of the most common infectious diseases in developed countries

The surfaces of the teeth and the gingival crevices carry large numbers of anaerobic bacteria. Plaque is a film of bacterial cells anchored in a polysaccharide matrix, which the organisms secrete. When teeth are not cleaned regularly, plaque can accumulate rapidly and the activities of certain bacteria, notably Streptococcus mutans, can lead to dental decay (caries), as acid fermented from carbohydrates can attack dental enamel. The prevalence of dental decay is linked to diet.

The pharynx and trachea carry their own normal flora

The flora of the pharynx and trachea may include both α- and β-haemolytic streptococci as well as a number of anaerobes, staphylococci (including Staph. aureus), Neisseria and diphtheroids. The respiratory tract is normally quite sterile, despite the regular intake of organisms by breathing. However, substantial numbers of clinically normal people may carry the fungus Pneumocystis jirovecii (previously known as P. carinii) in their lungs.

In the gut the density of microorganisms increases from the stomach to the large intestine

The stomach normally harbours only transient organisms, its acidic pH providing an effective barrier. However, the gastric mucosa may be colonized by acid-tolerant lactobacilli and streptococci. Helicobacter pylori, which can cause gastric ulcers (see Ch. 22), is carried without symptoms by large numbers of people, the bacterium being in mucus and neutralizing the local acidic environment. The upper intestine is only lightly colonized (10⁴ organisms/g), but populations increase markedly in the ileum, where streptococci, lactobacilli, enterobacteriaceae and Bacteroides may all be present. Bacterial numbers are very high (estimated at 10¹¹/g) in the large bowel, and many species can be found (Fig. 8.2). The vast majority (95–99%) are anaerobes, Bacteroides being especially common and a major component of faecal material; E. coli is also carried by most individuals. Bacteroides and E. coli are among the species capable of causing severe disease when transferred into other sites in the body. Harmless protozoans can also occur in the intestine (e.g. Entamoeba coli) and these can be considered as part of the normal flora, despite being animals.

Figure 8.2 The longitudinal distribution, frequency of occurrence and densities of the bacteria making up the normal flora of the human gastrointestinal tract.

The urethra is lightly colonized in both sexes, but the vagina supports an extensive flora of bacteria and fungi

The urethra in both sexes is relatively lightly colonized, although Staph. epidermidis, Strep. faecalis and diphtheroids may be present. In the vagina, the composition of the bacterial and fungal flora undergoes age-related changes:

A number of fungi occur, including Candida, which can overgrow to cause the pathogenic condition ‘thrush’ if the vaginal pH rises and competing bacteria diminish. The protozoan Trichomonas vaginalis may also be present in healthy individuals.

Some of the species of the normal flora are positively beneficial to the host

The importance of these species for health is sometimes revealed quite dramatically under stringent antibiotic therapy. This can drastically reduce their numbers to a minimum, and the host may then be over-run by introduced pathogens or by overgrowth of organisms normally present in small numbers. After treatment with clindamycin, overgrowth by Clostridium difficile, which survives treatment, can give rise to antibiotic-associated diarrhea or, more seriously, pseudomembranous colitis.

Ways in which the normal flora prevents colonization by potential pathogens include the following:

Gut bacteria also release organic acids, which may have some metabolic value to the host; they also produce B vitamins and vitamin K in amounts that are large enough to be valuable if the diet is deficient. The antigenic stimulation provided by the intestinal flora helps to ensure the normal development of the immune system.

What happens when the normal flora is absent?

Germ-free animals tend to live longer, presumably because of the complete absence of pathogens, and develop no caries (see Ch. 18). However, their immune system is less well developed and they are vulnerable to introduced microbial pathogens. At the time of birth, humans are germ free, but acquire the normal flora during and immediately after birth, with the accompaniment of intense immunologic activity.

The disadvantages of the normal flora lie in the potential for spread into previously sterile parts of the body

This may happen:

Members of the normal flora are important causes of hospital-acquired infection when patients are exposed to invasive treatments. Patients suffering burns are also at risk.

Overgrowth by potentially pathogenic members of the normal flora can occur when the composition of the flora changes (e.g. after antibiotics) or when:

Under these conditions, the potential pathogens take advantage of the opportunity to increase their population size or invade tissues, so becoming harmful to the host. An account of diseases associated with such opportunistic infections is given in Chapter 30.

Commensalism, mutualism and parasitism are categories of symbiotic association

All associations in which one species lives in or on the body of another can be grouped under the general term ‘symbiosis’ (literally ‘living together’). Symbiosis has no overtones of benefit or harm and includes a wide diversity of relationships. Attempts have been made to categorize types of association very specifically, but these have failed because all associations form part of a continuum (Fig. 8.3). Three broad categories of symbiosis – commensalism, mutualism and parasitism – can be identified on the basis of the relative benefit obtained by each partner. None of these categories of association is restricted to any particular taxonomic group. Indeed, some organisms can be commensal, mutualist or parasitic depending upon the circumstances in which they live (Fig. 8.4).

Figure 8.3 The relationships between symbiotic associations. Most species are independent of other species or rely on them only temporarily for food (e.g. predators and their prey). Some species form closer associations termed ‘symbioses’ and there are three major categories – commensalism, mutualism and parasitism – though each merges with the other and no definition separates one absolutely from the others.

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