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Frontiers in Microbiology - VIII. Microbes and Humans

If we consider a human being to be a collection of cells, then we are all 90 percent microbial! This conclusion is based on the estimate that within our bodies there are about 10 microbes for each human cell (ASM, 2004). Connections between human health and microbiology go all the way back to the discovery of microbes. The amateur Dutch scientist Antonie van Leeuwenhoek is credited with being the first to observe microbes in the late 17th century (DeKruif, 1926). Leeuwenhoek first observed microbes swimming in rainwater. He wondered if these "wretched beasties" fell from the sky or had a more earthly origin. To find out he performed a simple experiment. He scrupulously cleaned a porcelain bowl and set it out in the rain. He was careful to place the bowl up off the ground so that the splashing raindrops would not introduce dirt into the bowl. When he examined the fresh rainwater under his microscope, there were no beasties to be seen. He let the rainwater sit for several days and when he looked again, there they were. Thus, Leeuwenhoek demonstrated that the microbes did not come from the rain but from the earth.

Leeuwenhoek was also interested in how microbes interacted with humans. In one of his first investigations he examined some material taken from between his teeth and was fascinated to see more of his little beasties. Later, he encountered an old man with especially bad teeth. The old man explained to Leeuwenhoek that he had never in his life cleaned his teeth. Delighted to hear this, Leeuwenhoek persuaded the old man to come to his study so he could obtain samples to view through his microscope. He witnessed quite a show. Today, scientists estimate that the human mouth contains more than 700 different species of microbes (Pennisi, 2005). More than half of these species cannot be cultured in the laboratory.

Even humans who practice good hygiene are full of microbes. We don’t start out that way however. During the nine months we spend in our mother’s womb, we exist in a sterile environment. Not until we are born do we first encounter microbes: from our mothers, hospital personnel, and our surroundings. Then, very quickly, microbes begin to colonize our bodies in very specific ways. Many of these microbes perform activities that enhance the health of the individual. For example, microbes help digestion, synthesize nutrients, detoxify ingested toxins, kill invading bacteria, and help organs to grow larger. Animals that are raised in sterile environments to prevent exposure to microbes are less healthy than their microbe-colonized counterparts.

Some areas of human anatomy are home to enormous numbers of microbes, while others remain sterile. As shown in Table 1, the human body hosts approximately 1.25 kilograms (2.75 pounds) of microbes. This corresponds to more than 1 × 10¹⁴ individual cells. Aspects of these various microbe communities are described in Table 2.

Although microbes are important to our health, a small number of species can cause disease. Bubonic plague, cholera, syphilis, tuberculosis, dysentery, typhoid fever, and diphtheria are among the bacterial diseases that affect humans. How do we know when a microbe is the cause of a disease? Since the late 19^th century, medical researchers have used criteria developed by the German physician Robert Koch (see Table 3) to establish that a particular microbe causes a specific disease. More recent findings in microbiology are suggesting that Koch’s gold standard may sometimes be difficult or impossible to achieve.

Table 1

Take an upset stomach for example. We often attribute it to food poisoning. We know that a number of common species of bacteria such as Salmonella and E. coli can cause food poisoning. Stomachaches associated with ulcers, however, were long considered to be different. Until fairly recently, the prevailing wisdom was that stomach ulcers resulted from too much acid in the stomach, which was brought on by stress. The accepted treatment consisted of medication to neutralize stomach acid and the introduction of a bland diet.

Table 2

This stress-related view of stomach ulcers was challenged by two Australian scientists in 1982 (Blaser, 1996). Since Robert Koch’s time, scientists have seen bacteria associated with stomach ulcers. The bacteria were not thought to cause the ulcers, however. It was believed that the acidic conditions of the stomach would not support the growth of bacteria. Those bacteria that were observed were thought to result from contamination of the stomach samples.

Table 3

An Australian pathologist named J. Robin Warren had examined many gastric biopsies. He noticed that bacteria were always present in inflamed stomach tissues. Furthermore, the number of bacteria seen was correlated with the extent of the inflammation. He discussed his observations with a colleague named Barry Marshall. The two set out to isolate the bacteria and satisfy Koch’s postulates.

They tried to culture bacteria taken from stomach biopsies for more than one year without success. Then a fortunate accident occurred. It was their practice to incubate the bacterial cultures for two days and then look for growth. This time the Easter holiday interfered with their routine and the cultures were incubated for six days. When they finally removed the culture plates from the incubator and examined them, they saw vigorous bacterial growth. The bacteria were Helicobacter pylori, which require longer growth times than bacteria typically cultured in the laboratory.

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The two researchers were delighted with their serendipitous discovery. It did not, however, establish H. pylori as the cause of stomach ulcers. Koch’s postulates were not satisfied. In a bold and perhaps ethically questionable move, Marshall and another volunteer intentionally ingested cultures of H. pylori. Both developed stomach inflammation and H. pylori were successfully isolated from their stomach biopsies. A firm link was established between the bacteria and gastritis. Since neither scientist developed a stomach ulcer, that link remained unproven. Eventually, epidemiological studies confirmed that people with H. pylori infections were more likely to have stomach ulcers. The link was further strengthened when antibiotic treatments cured the ulcers. Eventually, in 2005, the two researchers received the Nobel Prize in medicine.

This example illustrates why Koch’s postulates may not be the best criteria for establishing a microbe as the cause of a disease. We cannot culture many microbes (and potential pathogens) in the laboratory. In the case of H. pylori, the two scientists were lucky to discover that the bacteria were slow-growing. In other cases, pathogenic microbes may live as part of a complex community that doesn’t permit them to be grown as pure cultures in the lab. As discussed earlier, newer techniques such as PCR have given scientists ways to establish links between a disease and a specific microbe, even when it can’t be grown in the lab.

Until the advent of antibiotics in the 1940s, bacterial infections were major killers, even in developed countries. Antibiotics were hailed as magic bullets, able to specifically obliterate disease-causing microbes. The first commercially developed antibiotic was penicillin. Within a few years of its introduction, bacteria resistant to the drug were observed. In fact bacteria resistant to antibiotics have been around long before their use in medicine. Scientists have found antibiotic-resistant bacteria in samples taken from artic glaciers. These bacteria were estimated to be more than 2000 years old.

Bacteria resistant to an antibiotic can pass on copies of their resistance gene to other bacteria through horizontal transfer. Over the past 50 years, antibiotics have been so widely used that infections once treatable by antibiotics are killing patients even in the United States. According to a Centers for Disease Control and Prevention (CDC) estimate, each year nearly two million people acquire a bacterial infection while in a hospital, resulting in approximately 90,000 deaths (Bren, 2003). Most of these bacteria are resistant to at least one of the antibiotics normally used to treat them.

The overuse of antibiotics contributes to the proliferation of resistant bacteria. Common infections such as colds and flus are caused by viruses. Antibiotics have no effect on them. Nevertheless, when people with colds or flus visit their doctor, they often receive prescriptions for antibiotics. To time-pressed physicians it is sometimes easier to just write the prescription that the patient wants rather than to explain why the antibiotic will not help. The CDC estimates that one-third of the outpatient prescriptions for antibiotics written in the United States are unnecessary (CNN.com Health, 2000). The problem of antibiotic-resistant bacteria must be addressed through education and research. The public needs to realize that the inappropriate use of antibiotics is dangerous. When prescribed for viral infections, antibiotics are of no benefit and contribute to the proliferation of resistant bacteria. For similar reasons, farmers need to restrict their use of antibiotics in animal feed. Finally, researchers need to carry on their quest to develop more and better antibiotics.

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