A cluster of Enterobacter cloacae bacteria Eye of Science / Science Source
Most of our microbes inhabit the colon, the final loop of intestine, where they help us break down fibers, harvest calories, and protect us from micro-marauders. But they also do much, much more. Animals raised without microbes essentially lack a functioning immune system. Entire repertoires of white blood cells remain dormant; their intestines don't develop the proper creases and crypts; their hearts are shrunken; genes in the brain that should be in the "off" position remain stuck "on." Without their microbes, animals aren't really "normal."
What do we do for our microbes in return? Some scientists argue that mammals are really just mobile digestion chambers for bacteria. After all, your stool is roughly half living bacteria by weight. Every day, food goes in one end and microbes come out the other. The human gut is roughly 26 feet in length. Hammered flat, it would have a surface area of a tennis court. Seventy percent of our immune activity occurs there. The gut has its own nervous system; it contains as many neurons as the spinal cord. About 95 percent of the body's serotonin, a neurotransmitter usually discussed in the context of depression, is produced in the gut.
Children raised in microbially rich environments—with pets, on farms, or attending day care—are at lower risk of allergic diseases.
So the gut isn't just where we absorb nutrients. It's also an immune hub and a second brain. And it's crawling with microbes. They don't often cross the walls of the intestines into the blood stream, but they nevertheless change how the immune, endocrine, and nervous systems all work on the other side of the intestine wall.
Science isn't always consistent about what, exactly, goes wrong with our microbes in disease situations. But a recurrent theme is that loss of diversity correlates with the emergence of illness. Children in the developing world have many more types of microbes than kids in Europe or North America, and yet generally develop allergies and asthma at lower rates than those in industrialized nations. In the developed world, children raised in microbially rich environments—with pets, on farms, or attending day care—have a lower risk of allergic disease than kids raised in more sterile environments.
Those who study human microbial communities fret that they are undergoing an extinction crisis similar to the one afflicting the biosphere at large—and that modern medicine may be partly to blame. Some studies find that babies born by C-section, deprived of their mother's vaginal microbes at birth, have a higher risk of celiac disease, Type 1 diabetes, and obesity. Early-life use of antibiotics—which tear through our microbial ecosystems like a forest fire—has also been linked to allergic disease, inflammatory bowel disease, and obesity.
Which brings us to the question more and more scientists are asking: If our microbiota plays a role in keeping us healthy, then how about attacking disease by treating the microbiota? After all, our community of microbes is quite plastic. New members can arrive and take up residence. Old members can get flushed out. Member ratios can shift. The human genome, meanwhile, is comparatively stiff and unresponsive. So the microbiota represents a huge potential leverage point in our quest to treat, and prevent, chronic disease. In particular, the "forgotten organ," as some call the microbiota, may hold the key to addressing our single greatest health threat: obesity.
PARESH DANDONA LEFT INDIA in 1966 for a Rhodes Scholarship at Oxford University. He became "the first colored guy," he says, to head his unit at the University of London hospital. His bearing—heels together, back stiff, and an orator's care with words delivered in a deep, sonorous voice—recalls a bygone era. He moved to Buffalo in 1991.
During those decades, the number of Americans considered obese nearly tripled. One-third of Americans are now considered overweight, and another third obese. Worldwide, one-fourth of humanity is too heavy, according to the World Health Organization. In 2011, the United Nations announced that for the first time ever, chronic diseases, most of which are linked to obesity, killed more people than infectious diseases. In the United States, obesity accounts for 20 percent of health care costs, according to Cornell University economists.
And the problems aren't limited to the obese themselves: Children born to obese mothers have hardened arteries at birth, a risk factor for cardiovascular disease. They have a greater risk of asthma. Some studies suggest they're more likely to suffer from attention deficit disorders and autism.
Why are we increasingly prone to obesity? The long-dominant explanation is simply that too little exercise and too many calories equals too much stored fat. The solution: more exercise and a lot more willpower. But there's a problem with this theory: In the developed world, most of us consume more calories than we really need, but we don't gain weight proportionally.
A pound of body fat contains roughly 3,500 calories. If you run a daily surplus of just 500 calories—the amount in a bagel with a generous serving of cream cheese—you should, judging by the strict calorie-in-must-equal-calorie-out model, gain a pound of fat per week. Most of us do run a surplus in that range, or even higher, but we either gain weight much more slowly, or don't gain weight at all.
Some corpulent people, meanwhile, have metabolisms that work fine. Their insulin and blood sugar levels are within normal range. Their livers are healthy, not marbled with fat. And some thin people have metabolic syndrome, often signaled by a beer gut. They suffer from fatty liver, insulin resistance, elevated blood sugar, high blood pressure, and low-grade, systemic inflammation. From a public health perspective, these symptoms are where the real problem lies—not necessarily how well we fit into our jeans.
Inflammation might not be a symptom of metabolic syndrome: It could be a cause.
Here's the traditional understanding of metabolic syndrome: You ate too much refined food sopped in grease. Calories flooded your body. Usually, a hormone called insulin would help your cells absorb these calories for use. But the sheer overabundance of energy in this case overwhelms your cells. They stop responding to insulin. To compensate, your pancreas begins cranking out more insulin. When the pancreas finally collapses from exhaustion, you have diabetes. In addition, you develop resistance to another hormone called leptin, which signals satiety, or fullness. So you tend to overeat. Meanwhile, fat cells, which have become bloated and stressed as they try to store the excess calories, begin emitting a danger signal—low-grade inflammation.
But new research suggest another scenario: Inflammation might not be a symptom, it could be a cause. According to this theory, it is the immune activation caused by lousy food that prompts insulin and leptin resistance. Sugar builds up in your blood. Insulin increases. Your liver and pancreas strain to keep up. All because the loudly blaring danger signal—the inflammation—hampers your cells' ability to respond to hormonal signals. Maybe the most dramatic evidence in support of this idea comes from experiments where scientists quash inflammation in animals. If you simply increase the number of white blood cells that alleviate inflammation—called regulatory T-cells—in obese mice with metabolic syndrome, the whole syndrome fades away. Deal with the inflammation, it seems, and you halt the dysfunction.