Bacteria have gotten a bad rap. From the Black Plague to the recent talk of germ warfare, bacteria have been perceived as microbial pariahs, which must be eliminated.
A new study may help to change the perception of bacteria as working against humans. At least one microorganism in the gut has been found to facilitate gene expression of a number of genes that assist intestinal development and digestive function.
The report came out in the February 2 issue of the journal Science. Jeffrey I. Gordon, M.D., who led the study, is the Alumni Professor and Head of the Department of Molecular Biology and Pharmacology at Washington University School of Medicine in St. Louis. The first author is Lora V. Hooper, Ph.D., an instructor in molecular biology and pharmacology and a recipient of a career development award from the Burroughs Welcome Fund.
“We live in a world predominated by microbes,” explains Gordon. “These organisms have co-evolved with their mammalian hosts over millions of years. During this time, they have been forced to become master physiologic chemists, and they have had to develop strategies for satisfying their own nutritional needs and various needs of their hosts. We wanted to figure out some of the lessons that they have learned about us, and how they contribute to our health.”
Hooper also said that the “majority of the bacteria that we have contact with on a daily basis are the ones that we carry around in our body and the number of microbial cells that you carry around with you probably exceeds the number of your own cells.”
The Mice Get It Again
To better understand how microbes affect another organism’s physiology, the researchers started off with mice that were germ-free.
They then inoculated the mice with Bacteroides thetaiotaomicron (B. theta for short), a bacterium normally found in healthy human and mouse intestines. Though E. coli may be the more famous intestinal microbe, B. theta is more abundant.
The researchers then used new molecular techniques to determine how the flora affected mouse genes. DNA micro-arrays or gene chips allowed them to determine the gene expression profiles for thousands of genes at the same time.
“We did not have a preconceived notion of how many intestinal functions are influenced by gut microbes,” noted Hooper. “Gene chips allowed us to survey, in a relatively unbiased way, the effects of a common gut microbe on more than 20,000 mouse genes.”
The team found that introducing B. theta into the germ-free mice changed the expression of a number of genes in the mice. Many of the genes play a role in the digestive physiology of the rodent.
Some of the genes affect absorption and metabolism of sugars and fats. B. theta also activated genes that control the integrity of the cellular barrier that lines the intestine and separates us from dangerous organisms and ingested substances. Other genes affected by the bacterium regulate how potentially toxic compounds are metabolized, how blood vessels are formed and how the gut matures during the post-natal period.
“Bacteria have a large impact on overall physiology,” Hooper said. “We were amazed at the breadth of normal intestinal functions affected by a single microbe.”
“One of our findings is that microbes are able to regulate intestinal genes involved in breaking down foods into simpler units that can be absorbed,” explained Gordon.
Hooper compared the mouse/bacterial interactions to a conversation. “What we ultimately want to know is what types of signals are emanating from the bacteria, how do they affect our cells, how does the immune system integrate the information they contribute to the cells, and how does the host affect bacterial physiology.”
“Shortly after birth, resident microbes begin to educate the gut’s immune system, signaling that they are safe, normal partners that do not merit an immune response,” says Gordon. “As well as preventing adverse responses to normal bacteria, this educational process might help ensure that we don’t react poorly to certain antigens we ingest.
When the alliance between microbe and host is upset, there may be serious consequences to human health. “We normally think of bacteria as something to be killed off,” said Hooper. “We really need to rethink that and to think carefully about the effects that antibiotics can have on our microbes.”
In the future, the team hopes to learn more about how normal bacteria develop an effective working relationship with humans. They would like to exploit the strategies developed by our microbes over the course of several million years to help identify new therapies for promoting health and for treating diseases that occur inside, or even outside, our gastrointestinal tract.

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