Of Microbes and Men
Bacteria disappearing from our bodies may harm human health
By Colin Nickerson, Globe Staff | February 25, 2008
CAMBRIDGE - Not feeling quite yourself?
No wonder. In a sense, you aren't really you.
Scientists estimate that 90 percent of the cells contained in the human body belong to nonhuman organisms - mostly bacteria, but also a smattering of fungi and other eensy entities. Some 100 trillion microbes nestle in niches from our teeth to our toes.
But what's setting science on its heels these days is not the boggling numbers of bugs so much as the budding recognition that they are much more than casual hitchhikers capable of causing disease. They may be so essential to well-being that humans couldn't live without them.
In this emerging view, humans and their microbes - or, as some biologists playfully put it, microbes and their attached humans - have evolved together to form an extraordinarily complex ecosystem.
"We're not individuals, we're colonies of creatures," said Bruce Birren, director of microbial sequencing at the Broad Institute, a research center affiliated with Harvard and the Massachusetts Institute of Technology. His team is part of a newly launched effort by the US National Institutes of Health to map the DNA and complete the first comprehensive census of microbial species that are inseparable from human existence.
"We can't take nutrition properly without bacteria. We can't fight bad germs without good germs," he said. "It may turn out that secretions from bacteria affect not only long-term health, but hour-by-hour moods - could a person's happiness depend on his or her bugs? It's possible. Our existences are so incredibly intertwined."
However, in the opinion of some researchers, this strange union may be headed for trouble because of profligate use of antibiotics and antiseptic lifestyles that deter the transfer of vital strains of bacteria that have swarmed in our systems at least since early humans ventured out of Africa.
Some strains of bacteria are disappearing from humans, especially in industrialized countries, and may be linked to germ-destroying substances in everything from hankies to hamburger.
"We're seeing the equivalent of global warming in the human ecosystem," said Dr. Martin J. Blaser, professor of microbiology and chairman of the department of medicine at New York University. "Changes of huge magnitude are occurring over a few generations. Nature famously abhors a vacuum - the bacteria disappearing from our systems ... might be replaced by or ganisms that aren't nearly as benign."
Since the late 19th century, when microbes were discovered, researchers have focused mostly on bacteria that cause disease.
"No one was paying too much attention to the vastly more numerous species [within the body] that do no harm and may be doing a great deal of good," said Roberto Kolter, professor of microbiology at Harvard Medical School and president-elect of the American Society of Microbiology. "Without these microbes, human beings would be in trouble."
The human gut, throat, mouth, skin, and other anatomical regions host thousands of species of microbes that have never been tallied, much less scrutinized. The bacteria and other microbial entities are tiny, so while they make up the huge majority of cells living on and within us, they are just a fraction of our overall bulk.
When the human genome was completed in 2003, scientists were stunned to realize that humans possessed only about 20,000 genes, far fewer than expected. In contrast, microbiologists estimate the microbes in our systems carry 3 million genes, with which we constantly exchange molecular substances involved in growth, development, and reproduction.
Under emerging theories, human development and behavior - as well as health - may be influenced by the genes of the species within. "We haven't got the hard evidence, but that's where the science is headed," said Kolter.
The new thinking grew partly from 1990 work by Norman Pace, a University of Colorado professor who used DNA analysis to show more biodiversity in an ounce of sediment from hot springs at Yellowstone National Park than scientists had previously suspected existed in the entire world. That inspired microbiologists to begin seeking DNA in all sorts of odd places - leading to discoveries that multiple species of bacteria thrive in areas, like the esophagus, long assumed inhospitable to life.
Until recent years, microbial science has been hindered by the fact that many strains of bacteria cannot be "cultured," or coaxed to reproduce in Petri dishes in the lab. That made them difficult to study using the time-honored tools of microscope and nutrients.
But now high-powered and relatively inexpensive DNA sequencing technology similar to that used to map the human genome is being turned on our microbes. A five-year Human Microbiome Project underway since last month will seek to turn a genetic spotlight on the thousands of species that pervade five regions of the anatomy - the digestive system, mouth, nose, skin, and female urogenital tract.
"The goal is to discover what microbial communities exist in different parts of the body and how these communities affect health and disease," said Lu Wang, program director for large scale sequencing at the National Human Genome Research Institute.
Not all of the body is infused with germs. The brain, blood system, and most organs appear to be microbe-free, say scientists.
Humans are born kicking, screaming - and sterile. The womb contains no germs, but the moment a new baby emerges it is colonized by rapidly multiplying microbes - from its mother's breast, from the clothes in which it is first swaddled, from the germ-imbued air of its first breath.
Not every baby acquires the same germs. A baby born by Caesarean section, for example, will pick up other germs than a baby delivered through the birth canal. And there are hints that acquiring the right combination of bacteria affects health in ways similar to inheriting good genes.
While the composition of the microbial swarms within humans varies in different parts of the world, some germs seem to have accompanied humans everywhere, and the waning presence of some of these bugs within inhabitants of the industrialized world is cause for puzzlement among researchers - and some alarm.
Take the stomach bacterium Helicobacter pylori, an ambivalent germ: It has been linked to ulcers and stomach cancers. But it also may guard against asthma and diseases of the esophagus, according to new research.
In Africa, 90 percent of children carry h. pylori in their stomachs. So did children in the United States, until a few decades ago.
The bacteria seem to be transferred within families who live in close proximity, sharing beds, eating utensils, and tight quarters. These days, only about 5 percent of American children harbor the bacteria - that's because US kids often grow up in small families, occupy private bedrooms, drink clean water, and scarf food from plates scoured in dishwashers using antibacterial soaps.
One good consequence is that stomach disease is on the decline in the West, say researchers.
But diseases of the esophagus, allergies, and childhood asthma are on the rise. And research by Blaser and NYU epidemiologist Yu Chen suggests that h. pylori provided protection against esophageal diseases - including cancer - as well as asthma. Their study last year of 7,663 adults found that those who carried the bacteria were 40 percent less likely to have had asthma under age 15 than those who didn't host it."What we see, for certain, is that human micro-ecology is changing right under our noses," said Blaser. "This bacterium has been the dominant organism in our stomach for tens of thousands of years. Now it's disappearing. I suspect if [h. pylori] was totally bad for us, it wouldn't have been there. So I think the disappearance will have consequences. You can compare this to changes occurring in the world environment - species that may be vital are vanishing too fast."