A bacterium that lives in the human gut adaptively shifts more than a quarter of its genes into high gear when its host's diet changes from sugar to complex carbohydrates.
This adaptive mechanism not only allows the bacterial species to survive rapidly changing nutrient conditions but also helps maintain the functions and stability of the gut's highly complex microbial society, according to researchers at Washington University School of Medicine in St. Louis.
Their findings are reported in the March 25, 2005 issue of the journal Science.
"Bacterial cells in the human gut number close to 100 trillion," says Jeffrey Gordon, M.D., director of the Center for Genome Sciences at Washington University and professor of molecular biology and pharmacology. "Together, these microbes can be viewed as a 'microbial organ' that lives within the intestine and harvests, stores and redistributes energy from the diet."
Because changes in the composition of this "microbial organ" may be deleterious to human health, it is important to understand how gut microbes adapt to the dynamic environment of the gut and ensure the functional stability of the intestinal bioreactor, the researchers say. In addition, variations in the composition of gut microbial communities among different people may be an important factor that influences predisposition to obesity and obesity-related disorders such as diabetes and heart disease
The bacterium of the study, called Bacteriodes thetaiotaomicron or B. theta, is among the most abundant species in the human gut microbial community. B. theta breaks down otherwise indigestible carbohydrates, such as dietary fiber, and supplies its host with nutrients while obtaining food for itself and other gut bacterial species. The complete genome sequence of B. theta was generated two years ago in the same laboratory.
The researchers inoculated germ-free mice, who have no intestinal bacteria, with B. theta. The mice were fed a diet high in complex carbohydrates and low in simple sugars. Ten days later, the activity of all genes in the bacterial genome was surveyed in B. theta from the mice's guts.
The research team found that 1,237 of the bacterium's 4,779 genes were highly active compared to B. theta grown in a simple-sugar soup. The predominant group of high-activity genes were involved in the acquisition and digestion of carbohydrates.
"In mice fed complex carbohydrates, we found that the microbes attached to small food particles in the intestine," Gordon says. "These carbohydrate-rich particles are the bacteria's dining room tables. By generating a series of carbohydrate-binding proteins on its outer surface, B. theta is able to hold onto a seat at the table. The bacterium also produces the necessary utensils to break different types of carbohydrate chains into 'bite-sized' pieces; the utensils are a variety of enzymes directed at different types of carbohydrates."
When a set of germ-free mice were fed a simple-sugar diet--instead of a complex-carbohydrate diet--and then inoculated with B. theta, the genome activity analysis showed that B. theta had adaptively switched on a different set of genes encoding surface proteins and carbohydrate-busting enzymes. This switch allowed B. theta to bind to and digest the host-produced mucus carbohydrates.