Caution: Killing Germs May Be Hazardous to Your Health

Microbes play an important role in digestion, especially of polysaccharides, starch molecules found in foods such as potatoes or rice that may be hundreds or thousands of atoms long. The stomach and intestines secrete 99 different enzymes for breaking these down into usable 6-carbon sugars, but the humble gut-dwelling Bacterioides theta produces almost 250, substantially increasing the energy we can extract from a given meal.

Of course, "energy" is another way of saying "calories." Jeffrey Gordon of Washington University raised a colony of mice in sterile conditions, with no gut microbes at all, and although they ate 30 percent more food than normal mice they had less than half the body fat. When they were later inoculated with normal bacteria, they quickly gained back up to normal weight. "We are finding that the nutritional value of food is pretty individualized," Gordon says. "And a big part of what determines it is our microbial composition."

We can't raise humans in sterile labs, of course, but there's evidence that variations between people in their intestinal microbes correspond to differences in body composition. And other factors appear to be at work besides the ability to extract calories from starch. Bacteria seem able to adjust levels of the hormones ghrelin and leptin, which regulate appetite and metabolism. Certain microbes even seem to be associated with a desire for chocolate, according to research by the Nestlé Research Center. And a tiny study suggests that severe emotional stress in some people triggers an explosion in the population of B. theta, the starch-digesting bacteria associated with weight gain. That corresponds to folk wisdom about "stress eating," but it is also a profoundly disturbing and counterintuitive observation that something as intimate as our choice between a carrot and a candy bar is somehow mediated by creatures that are not us.

But these are the closest of aliens, so familiar that the immune system, which ordinarily attacks any outside organism, tolerates them by the trillions—a seeming paradox with profound implications for health. The microbes we have all our lives are the ones that colonize us in the first weeks and months after birth, while our immune system is still undeveloped; in effect, they become part of the landscape. "Dendritic" (treelike) immune cells send branches into the respiratory and digestive tracts, where they sample all the microbes we inhale or swallow. When they see the same ones over and over, they secrete an anti-inflammatory substance called interleukin-10, which signals the microbe-killing T-cells: stand down.

And that's an essential step in the development of a healthy immune system. The immune reaction relies on a network of positive and negative feedback loops, poised on a knife edge between the dangers of ignoring a deadly invader and over-reacting to a harmless stimulus. But to develop properly it must be exposed to a wide range of harmless microbes early in life. This was the normal condition of most human infants until a few generations ago. Cover the dirt on the floor of the hut, banish the farm animals to a distant feedlot, treat an ear infection with penicillin, and the inflammation-calming interleukin-10 reaction may fail to develop properly. "Modern sanitation is a good thing, and pavement is a good thing," says Sachs, "but they keep kids at a distance from microbes." The effect is to tip the immune system in the direction of overreaction, either to outside stimuli or even to the body's own cells. If the former, the result is allergies or asthma. Sachs writes that "children who receive antibiotics in the first year of life have more than double the rate of allergies and asthma in later childhood." But if the immune system turns on the body itself, you see irritable bowel syndrome, lupus or multiple sclerosis, among the many autoimmune diseases that were virtually unknown to our ancestors but are increasingly common in the developed world.

That is the modern understanding of the "Hygiene Hypothesis," first formulated by David Strachan in 1989. In Strachan's original version, which has unfortunately lodged in the minds of many parents, actual childhood illness was believed to exert a protective effect. There was a brief vogue for intentionally exposing youngsters to disease. But researchers now believe the key is exposure to a wide range of harmless germs, such as might be found in a playground or a park.