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Other bacteria, including a number of foodborne pathogens (e.g., E. coli, Salmonella, and Campylobacter), have a response to acid that makes them better able to survive for short periods of time at pH 4 (acid tolerance response). This is higher than the pH of the stomach interior, so how could it be protective? One speculation is that bacteria ingested in foods are protected from the full impact of stomach acid by the buffering capacity of the food, although they would still be exposed to conditions well below pH 7. Even though they still cannot survive in the stomach for prolonged periods of time, the bacteria capable of mounting an acid tolerance response may be able to survive long enough to reach the small intestine.
That many bacteria do not survive passage through the stomach to areas more favorable for bacterial growth, like the small intestine and colon, shows how the acidic environment of the stomach lumen does not just contribute to the digestion of food, but also acts as a protective barrier. Another indicator of the protective effect of the acidic environment of the stomach is that people who have achlorhydria, a condition that results in a less acidic stomach pH, have increased susceptibility to infections of the lower intestinal tract. Likewise, the U.S. Food and Drug Administration (FDA) has cited the widespread use of proton-pump inhibitor (PPI) drugs that block gastric acid production and reduce stomach acidity as a potential risk for increased intestinal infection.
For those bacteria that manage to survive the acid barrier of the stomach, bile salts await them in the small intestine and colon. Bile salts are steroids with detergent-like properties that are produced in the liver, stored in the gallbladder, and then released through the bile duct into the intestine when food is passing through. Bile salts help neutralize the stomach acid and are used to emulsify lipids in food to enable fat digestion and absorption through the intestinal wall. The detergent-like properties of bile salts help disrupt bacterial membranes, especially those of Gram-negative bacteria.
An equally important protection of the small intestine is the rapid flow of contents through the small intestine. This rapid flow, together with the bile salts and the rapid turnover of intestinal mucosal cells, helps keep high concentrations of bacteria from developing in the small intestine. High concentrations of bacteria would not only increase the chance that bacteria could invade the small intestinal mucosa, but also allow bacteria to compete more effectively for the nutrients (e.g., simple sugars, amino acids) that the small intestine is designed to absorb. In the colon, the flow rate of contents is drastically reduced compared to the flow rate in the small intestine. Some scientists have compared the difference to the passage from a rapidly flowing stream (small intestine) to a nearly stagnant pond (colon).
The importance of the rapid flow rate of contents through the small intestine as a protection against bacterial colonization is underscored by the fact that bacterial pathogens that cause intestinal infections such as gastroenteritis (diarrhea and pain) generally are able to swim to the mucosa of the small intestine and attach to the mucosal cells, thus keeping them from being washed out of the colon. Another illustration of the importance of rapid flow of contents is the fact that people who develop blind loops, or regions of outpouching that have rather stagnant contents, have problems due to the buildup of bacteria within those regions. At one time, the intentional surgical introduction of blind loops in the small intestine was tried as a means of weight reduction. Not surprisingly, a side effect of this in some people was the development of sepsis caused by an invasion of some of the bacteria that reached high concentrations in the blind loop and were thus better able to penetrate the fragile mucosal layer.
Special Defenses of the Urogenital Tract
The female and male urogenital tracts (Figure 2-8) offer different environments and so different bacteria are associated with the different areas. As with other mucosal areas, the epithelial layer of the urinary tract system (the kidneys, ureters, bladder, and urethra) is protected by secretion of mucin, blocking the bacteria from gaining access to the surface. The bladder is typically sterile in both males and females, and a number of defenses protect the urinary tract. The urethra sphincter prevents further ascent of the bacteria to the bladder and kidney. Urine itself is antiseptic, and flushing of the bladder with urine helps remove bacteria that manage to ascend the urethra. The prostate gland in men secretes defensins.
Figure 2-8. Comparison of the female and male urogenital tracts. Anatomical differences between the female and male urogenital tracts result in different environments and physical barriers that lead to different bacteria colonizing different sites. Physical barriers include a sphincter at the opening of the urethra that prevents ascent of microbes to the bladder and kidney. The urethra is shorter in females than males. Flushing of the bladder and urethra with urine removes adherent bacteria. Secretion of mucin blocks microbes from gaining access to the epithelial surface. A cervical mucus plug protects the uterus and fallopian tubes in females. Lactobacillus species, major resident bacteria in healthy females, protect the vaginal cavity from other bacteria that might enter from the anal area, which is relatively close to the vaginal opening. Sexually active partners exchange their resident microbiota with each other.
Altered conditions, such as pH changes or obstructions, can facilitate certain pathogens (e.g., E. coli, Proteus mirabilis, Staphylococcus saprophyticus, and Klebsiella species) to colonize the urethra and cause urinary tract infections (UTIs), especially in women. Almost 95% of UTIs are attributed to bacteria that normally reside at the opening of the urethra and travel up to the bladder and occasionally as far as the kidney. Women are more likely to get UTIs because in females the urethra is much shorter and closer to the anus. Some anatomical obstructions of the ureter or the urethra, such as prostate enlargement, kidney transplant, or bladder or kidney dysfunction, as well as indwelling catheter use, can impair bacterial clearance by urine and promote bacterial growth and infection.
In the vagina, a cervical plug protects the uterus and fallopian tubes from invasion by bacteria. The vagina is lined by a stratified epithelium, which produces a variety of protective defense mechanisms, including lysozyme, lactoferrin, small antimicrobial cationic peptides, and proteins (such as secreted IgA and IgG antibodies, secretory leukocyte protease inhibitors, and various cytokines and chemokines). The resident microbiota plays an important protective function against pathogens in the female genital tract. The application of molecular sequencing technologies over the past decade has contributed greatly to our understanding of urogenital microbiome composition and dynamics. In sexually active partners, the microbiota exchange freely and influence each other. There are also age-specific changes to the microbiomes and immune functions that occur, especially in response to hormones in women. Resident vaginal bacteria are thought to help prevent acquisition of sexually transmitted infections, such as HIV.
Lactobacillus species are the major resident vaginal bacteria found in healthy humans. Lactobacillus bacteria ferment glycogen, which is abundantly produced in the vaginal tract. These bacteria produce hydrogen peroxide and lactic acid, which helps maintain a weakly acidic (pH 4–5) environment that serves to inhibit the growth of other microbes, thereby preventing infection by yeast (vulvovaginal candidiasis or vaginitis) and bacteria (bacterial vaginosis). Humans are unique among primates in having a vaginal microbiome dominated by Lactobacillus species, though it is not known why. How the vaginal mucosa tolerates chronic colonization with Lactobacillus species, while still protecting against colonization by other microbes, is an area of active research.
Special Defenses of the Respiratory Tract
The respiratory system is comprised of a ciliated epithelial cell layer that is interspersed with goblet cells that secrete mucin. In the respiratory tract (as well as in the fallopian tubes of the vaginal tract), there are specialized ciliated columnar cells, whose elongated protrusions (cilia) continuously wave in the same direction. The waving action of the cilia propels mucus blobs out of the area. Airway epithelial cells also secrete collectins (collagen-containing
