The Environment Within: Exploring the Role of the Gut Microbiome in Health and Disease
Lindsey Konkel, Jayne Danska, Sarkis Mazmanian, Lisa Chadwick, Environ Health Perspect. 2013;121(9):a276-a281.
The human genome codes for approximately 23,000 genes,  yet some experts have suggested that the total information coded by the human genome alone is not enough to carry out all of the body's biological functions.  A growing number of studies suggest that part of what determines how the human body functions may be not only our own genes, but also the genes of the trillions of microorganisms that reside on and in our bodies.
The genomes of the bacteria and viruses of the human gut alone are thought to encode 3.3 million genes.  "The genetic richness and complexity of the bugs we carry is much richer than our own," says Jayne Danska, an immunologist at the Hospital for Sick Children Research Institute in Ontario, Canada. "They serve as a buffer and interpreter of our environment. We are chimeric organisms."
A role for gut microbes in gastrointestinal function has been well documented since researchers first described differences in the fecal bacteria of people with inflammatory bowel disease.  The molecular mechanisms responsible for the gut microbiome's impact on metabolism and diseases throughout the body remain largely unknown. However, researchers are beginning to decipher how the microorganisms of the human intestinal tract influence biological functions beyond the gut and play a role in immunological, metabolic, and neurological diseases.
A New Normal
Early research on microbiota focused largely on the commensal bacteria that reside in the human gut. Commensal gut bacteria supply nutrients, help metabolize indigestible compounds, and defend against colonization by nonnative opportunistic pathogens.
But the distinction between "good" microbes that aid health and "bad" pathogenic microbes that cause disease has become blurred in recent years. Researchers have shown that under certain conditions, some types of normal gut bacteria can trigger disease. Sarkis Mazmanian, a microbiologist at the California Institute of Technology, dubbed these elements "pathobionts"; the term "pathogens," in contrast, refers to opportunistic microbes that are not normally part of the gut microbial community. 
Disturbances to the microbial equilibrium of the gut may mean that some microbes become overrepresented while others are diminished. "It's like a garden—you're less likely to have weeds growing if you have lush vegetation, but without this vegetation the weeds can potentially take over," Mazmanian says. When the gut moves toward a state of microbial imbalance, normally benign gut microbes may begin to induce inflammation and trigger disease throughout the body, even in the nervous system.
Researchers have long postulated that gut bacteria influence brain function. A century ago, Russian embryologist Elie Metchnikoff surmised that a healthy colonic microbial community could help combat senility and that the friendly bacterial strains found in sour milk and yogurt would increase a person's longevity. [6,7]
In 2011 Mazmanian and colleagues reported that changes in gut microbial composition might have far-ranging effects that extend to the brain.  They worked with germ-free ("gnotobiotic") mice, which are born in sterile environments and are not naturally colonized with microbiota.