28 JUNE 2007
The benefits of being outnumbered
Count the number of cells in your body, and multiply by 10. Now you have the approximate population of bacteria living in your gastrointestinal tract -- your gut, for short. Some of these bacteria may cause disease, but most of them are needed for digesting food, clotting blood, and crowding out pathogenic bacteria.
The adult gut hosts hundreds of species of bacteria. Numbering well into the trillions, these uncountable bacteria scrap for biochemical advantage in the giant, organic Mixmaster we call the GI tract, and we are the main beneficiaries of all this jostling.
It may be shocking to learn that human health, even life, depends on the contentious elbow-work among a sea of microbes, but when bacteria are scoured out of mouse guts, the animal's immune system and heart both develop abnormally.
Think of this next time you say, "ugh, bacteria!"
Humans are born sterile, so how do bacteria come in from the cold and occupy the stomach and intestines? What accounts for the change in their populations over time?
Insight into these questions come from a new study in PLOS-Biology, which tracked bacteria in the human gut by studying poop from 14 healthy newborns during the first 12 months of life. The authors used a microarray, also called a gene chip, to identify bacteria based on their DNA fingerprints in poop lovingly harvested by the mothers. Gene chips identify scraps of DNA. Since bacteria often appear distressingly alike, and many refuse to grow in the laboratory, gene chips are the preferred means for identifying them.
The researchers found that bacteria appear in the diaper within one to seven days, and the pioneering species tend to arrive in tour groups, not as lone species. According to lead author Chana Palmer, "I don't think we ever saw a monoculture," on the gene chips. Palmer, now scientific director of the Canary Foundation, did the study for her Ph.D. thesis at Stanford University, under the guidance of Patrick Brown, a professor of biochemistry and a Howard Hughes Medical Institute researcher.
Photo: Public Library of Science
Before long, the bacterial ecosystem turned from simple to bewildering, as dozens, even hundreds, of species battled to occupy the intestines, their populations roller-coastering according to some unfathomable logic. "The rapid, unexplained shifts in flora show that we don't understand very well what is going on," says Palmer. The sudden rise of certain species is "probably due to environmental exposure to bacteria that happened to be really capable of taking over."
Graphs: See "Development of the Human Infant..." below.
But particular bugs do not dominate for long, she added. "It seems that something happens really quickly to establish a new equilibrium, but it's not self-evident which bacteria drove it because no one species dominated afterwards."
Death by antibiotics
One obvious cause of change in gut flora is the use of antibiotics, and when used right after birth, antibiotics did delay the colonization. "It does look like it stalls development," says Palmer, "but the flora do kick in as soon as the antibiotics are removed ... and they ended up fine in the end."
However, at least in one case when a baby took antibiotics in the middle of the study, the drug obliterated an entire gutful of bugs. "Within our sensitivity limits, we could not measure any bacteria," says Palmer.
Given the multiple ways that bacteria help us survive, that finding is significant, says David Relman, an associate professor of medicine and of microbiology and immunology at Stanford, and co-investigator in the study. "These were fairly dramatic effects. I am fairly concerned about the breadth and magnitude of the effects in terms of the potential medical impact on the child."
As Relman notes, we humans and our gut-dwellers are caught in a mutualistic (you-scratch-my-back-and-I'll-scratch-your's) relationship, so "Anything that damages one partner has the potential for damaging the other participant."
The blasting of beneficial bacteria can leave a niche for pathogens like the yeast Candida, and Clostridium dificile, a bacterium that can be deadly. "I am a clinician, and we see all too often the adverse effects" of using -- and especially overusing-- antibiotics," Relman says.
Courtesy ©David Tenenbaum
In the end, it's rather surprising that despite the enormous variation in bacterial genetics, baby genetics, and environmental exposures, the basic bacterial brews in the 14 one-year-olds had many essential similarities. "It was sort of all a wash," says Palmer. "It's almost a forgone conclusion about where you end up because those are the bacteria that will thrive in the adult gut."
Relman, who says he was surprised at the seemingly random identity of the early-arriving bacteria, says the ecosystem eventually seems to take over. "There is increasing evidence that certain communities are favored. Soon after birth, the particular organisms that come to populate the gut, have in essence, chosen each other."
The gut flora are complex, but not random, he adds. Soil microbes are far more diverse, genetically, than those living in the human GI tract. "Outside, there are many more branches on the tree of DNA, but in the gut, there are few big branches. Somehow the human gut has co-evolved with particular organisms that it allows to prosper in its particular environment."
-- David Tenenbaum
• Development of the Human Infant Intestinal Microbiota, Chana Palmer et al, PLoS Biology | www.plosbiology.org 0001 July 2007 | Volume 5 | Issue 7 | e177.
• Raising germ-free mice