The Microbial Health Factor

Abstract

Trillions of commensal bacteria cover almost all environmentally exposed surfaces of our bodies at all times. But what are they doing? And why? If you want to understand the impact of commensal organisms on mammals, a good place to start is with mice that are devoid of all bacteria. When I started working on this problem in 2002, so few people were still familiar with the germ-free mouse models that I had to persuade a retired research technician to help me set up sterile chambers and teach me the ways of "sanitary engineering." Rather than the old steel and glass contraptions that he had used in his day (50 years ago), we were able to procure nicely modernized chambers with plastic bubbles that held up to four mouse cages. After my first few chamber contaminations, I began to understand why researchers rarely use germ-free animals. Germ-free animals were conceived of almost a century ago, but were not successfully raised until 1945. James A. Reyniers' group at the University of Notre Dame was the first to successfully raise and study germ-free animals. Perhaps reflecting a new fervor over hygiene, researchers concluded that wiping a mammal clean of microbes might actually be a good thing. The adult mice grew enormous bellies, stemming from digestive problems, but other than that, they seemed just as healthy and lived just as long as typical mice. In those days, science's relationship with bacteria was adversarial-the main purpose of a microbiologist was to study infectious disease. No one seemed too curious about what the seemingly passive commensal bacteria were doing. Indeed, 20 Nobel Prizes have been awarded for research on the immune response to harmful microbes, from tuberculosis to Helicobacter pylori, the causative agent of gastric ulcers. But in the grand scheme of things, bacterial infections are rare and opportunistic. Of the over 300,000 known bacterial species and possibly millions more, only about 170 are known to be pathogenic in mammals. When I trained as a microbiologist around the year 2000, the focus was still on pathogenic bacteria. But I became intrigued by the potential benefits of good bacteria. After all, we've co evolved with symbiotic bacteria for millions of years. The hygiene hypothesis, proposed in 1989 by David Strachan, correlated lower environmental exposure to microbes-as seen in developed countries-with higher rates of allergies. The idea made sense to me. Commensal bacteria help keep pathogenic bacteria at bay, and in the late 1990s new research was beginning to show that symbionts also contribute to the development of the intestinal architecture. If bacteria were so crucial to development, what else might they do? Could they actually make us healthier? Challenging though it was, I was convinced the best way to learn about the systemic effects of bacteria was to start with mice that lacked them entirely.

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