The human body offers a seemingly endless variety of microenvironments and niches, with variations in temperature, pH, nutrients, moisture, and oxygen tension from one area to another. With such a wide range of habitats, it should not be surprising that the body supports an abundance of microbes. In fact, it is so favorable that our bodies hold three times more microbes than our own cells. The importance of this relationship has recently become the focus of a comprehensive initiative (13.1 Making Connections).
As shown in table 1, most areas of the body in contact with the outside environment harbor resident microorganisms. Mucosal surfaces provide a particularly attractive surface for attachment. Most other body sites, including internal organs, tis sues, and the fluids they contain, are generally microbe-free (table 2). In fact, the presence of microbes in these areas is usually indicative of infection.
Table1. Sites that Harbor Normal Resident Microbes
Table2. Sterile (Microbe-Free) Anatomical Sites and Fluids
The vast majority of microbes that come in contact with the body are removed or destroyed by the host’s defenses long before they are able to colonize a particular area. Those organisms that occupy the body for only short periods are known as transients. The remaining microbes that do become established more permanently are considered residents. One of their most important adaptations is to avoid the attention of the body’s defenses. The resident organ isms have coevolved along with their human hosts toward a com plex relationship in which the effects of normal microbiota are generally not harmful to the host, and vice versa.
Although generally stable, the microbiota fluctuates with general health, age, variations in diet, hygiene, hormones, and drug therapy. In many cases the microbiota actually benefits the human host by preventing the overgrowth of harmful microorganisms. A common example is the fermentation of glycogen by lactobacilli, which keep the pH in the vagina acidic enough to prevent the overgrowth of the yeast Candida albicans and other pathogens. A second example is seen in the large intestine, where a protein produced by Escherichia coli can prevent the growth of pathogenic bacteria such as Salmonella and Shigella.
The generally antagonistic effect that “good” microbes have against intruder microorganisms is called microbial antagonism. The microbiota that exists in an established biofilm is unlikely to be displaced by incoming microbes. This antagonistic protection may simply be a result of a limited number of attachment sites in the host site, all of which are stably occupied by normal microbiota. Antagonism may also result from the chemical or physiological environment created by the resident microbiota, which is hostile to other microbes.
In experiments performed with mice, scientists discovered that a species of the intestinal bacterium Bacteroides controlled the host’s production of a defense compound that suppressed other microbes in the area. This is an extreme case of microbial antagonism, but the general phenomenon is of great importance to human health.
Generally the normal residents will have beneficial or benign effects only if the host is in good health with a fully functioning immune system, and if the microbiota remain in their natural microhabitats within the body. Hosts with compromised immune systems could very easily be infected by these residents (see table 3). We see this outcome when AIDS patients develop recurring bouts of pneumonia from Streptococcus pneumoniae, often carried as normal residents in the nasopharynx. Other micro biota-associated infections can occur when residents are introduced to a site that was previously sterile, as when E. coli from the large intestine gets into the bladder, resulting in a urinary tract infection.
Table3. Factors that Weaken Host Defenses and Increase Susceptibility to Infection*
Initial Colonization of the Fetus and Newborn
It has long been the consensus that the uterus and its contents are normally sterile during embryonic and fetal development and remain germ-free until just before birth.
Beginning with the rupturing of the amniotic sac several hours prior to birth, the baby is exposed to microbes carried by the mother. Even more extensive exposure occurs during the birth process itself, when the baby unavoidably comes into intimate contact with the birth canal. Within 8 to 12 hours after delivery, the newborn typically has been colonized by bacteria such as streptococci, staphylococci, and lactobacilli, acquired primarily from its mother. The skin, gastrointestinal tract, and portions of the respiratory and genitourinary tracts all continue to be colonized as contact continues with family members, health care personnel, the environment, and food. While this is the accepted view of most scientists, new techniques have pointed toward possible colonization of the fetus far before birth (see Clinical Connections: “Bacteria Before Birth?”).
The nature of the microbiota initially colonizing the large intestine is greatly influenced by whether the baby receives breast milk or formula. Milk and breast tissues contain their own microbiomes that seed the baby’s digestive tract with beneficial bacteria. A surprising part of neonatal research has revealed that breast milk contains short carbohydrate chains (oligosaccharides) that cannot be digested by the infant. Only certain species of Bifidobacterium (infantis) produce enzymes to break them down. This ensures that the milk selects for the growth of these beneficial bacteria, and the baby’s GI tract will become populated almost exclusively by them. It is likely that these bacteria provide protection against colonization by potentially harmful species and invasion by pathogens. In contrast, bottle-fed infants (receiving milk or a milk-based formula) tend to acquire a mixed population of coliforms, lactobacilli, enteric streptococci, and staphylococci. This combination is similar to an adult’s microbiota and does not offer the same protective effect.
Milestones that contribute to further development of the microbiota are weaning, eruption of teeth, and introduction of the first solid food. Although exposure to microbes is unavoidable and even necessary for the maturation of the infant’s microbiome, contact with pathogens is dangerous. The immune defenses of neonates have not yet fully developed, which makes them extremely susceptible to infection.
