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Are Happy Gut Bacteria Key to Weight Loss?

Imbalances in the microbial community in your intestines may lead to metabolic syndrome, obesity, and diabetes. What does science say about how to reset our bodies?

| Mon Apr. 22, 2013 6:00 AM EDT

A few years before Super Size Me hit theaters in 2004, Dr. Paresh Dandona, a diabetes specialist in Buffalo, New York, set out to measure the body's response to McDonald's—specifically breakfast. Over several mornings, he fed nine normal-weight volunteers an egg sandwich with cheese and ham, a sausage muffin sandwich, and two hash brown patties.

Dandona is a professor at the State University of New York-Buffalo who also heads the Diabetes-Endocrinology Center of Western New York, and what he observed has informed his research ever since. Levels of a C-reactive protein, an indicator of systemic inflammation, shot up "within literally minutes." "I was shocked," he recalls, that "a simple McDonald's meal that seems harmless enough"—the sort of high-fat, high-carbohydrate meal that 1 in 4 Americans eats regularly—would have such a dramatic effect. And it lasted for hours.

Inflammation comes in many forms. The swelling of a sprained ankle indicates repairing torn muscle and tendon. The redness and pain around an infected cut signifies the body's repulsion of microbes. The fever, aches, and pains that accompany the flu represent a body-wide seek-and-destroy mission directed against an invading virus. They're all essential to survival, the body's response to a perceived threat or injury. But inflammation can also cause collateral damage, especially when the response is overwhelming—like in septic shock—or when it goes on too long.

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Chronic, low-grade inflammation has long been recognized as a feature of metabolic syndrome, a cluster of dysfunctions that tends to precede full-blown diabetes and that also increases the risk of heart disease, stroke, certain cancers, and even dementia—the top killers of the developed world. The syndrome includes a combination of elevated blood sugar and high blood pressure, low "good" cholesterol, and an abdominal cavity filled with fat, often indicated by a "beer belly." But recently, doctors have begun to question whether chronic inflammation is more than just a symptom of metabolic syndrome: Could it, in fact, be a major cause?

For Dandona, who's given to waxing grandiloquent about the joys of a beer on the porch in his native Delhi, or the superb ice wines from the Buffalo region, the results presented a quandary. Food was a great pleasure in life. Why would Nature be so cruel, he wondered, and punish us just for eating?

Over the next decade he tested the effects of various foods on the immune system. A fast-food breakfast inflamed, he found, but a high-fiber breakfast with lots of fruit did not. A breakthrough came in 2007 when he discovered that while sugar water, a stand-in for soda, caused inflammation, orange juice—even though it contains plenty of sugar—didn't.

The Florida Department of Citrus, a state agency, was so excited it underwrote a subsequent study, and had fresh-squeezed orange juice flown in for it. This time, along with their two-sandwich, two-hash-brown, 910-calorie breakfast, one-third of his volunteers—10 in total—quaffed a glass of fresh OJ. The non-juice drinkers, half of whom drank sugar water, and the other half plain water, had the expected response—inflammation and elevated blood sugar. But the OJ drinkers had neither elevated blood sugar nor inflammation. The juice seemed to shield their metabolism. "It just switched off the whole damn thing," Dandona says. Other scientists have since confirmed that OJ has a strong anti-inflammatory effect.

Orange juice is rich in antioxidants like vitamin C, beneficial flavonoids, and small amounts of fiber, all of which may be directly anti-inflammatory. But what caught Dandona's attention was another substance. Those subjects who ate just the McDonald's breakfast had increased blood levels of a molecule called endotoxin. This molecule comes from the outer walls of certain bacteria. If endotoxin levels rise, our immune system perceives a threat and responds with inflammation.

If theories about the interplay of food and intestinal microbes pan out, it could help cure obesity and revolutionize the $66 billion weight loss industry.

Where had the endotoxin come from? One possibility was the food itself. But there was another possibility. We all carry a few pounds' worth of microbes in our gut, a complex ecosystem collectively called the microbiota. The endotoxin, Dandona suspected, originated in this native colony of microbes. Somehow, a greasy meal full of refined carbohydrates ushered it from the gut, where it was always present but didn't necessarily cause harm, into the bloodstream, where it did. But orange juice stopped that translocation cold.

Dandona's ongoing experiments—and others like it—could upend much of we thought we knew about the causes of obesity, or just that extra pesky 10 pounds of flab. If what some scientists now suspect about the interplay of food and intestinal microbes pans out, it could revolutionize the $66 billion weight loss industry—and help control the soaring $2.7 trillion we spend on health care yearly. "What matters is not how much you eat," Dandona says, "but what you eat."
 

EVER SINCE THE DUTCH DRAPER Antonie van Leeuwenhoek first scrutinized his own plaque with a homemade microscope more than three centuries ago and discovered "little living animalcules, very prettily a-moving," we've known that we're covered in microbes. But as new and cheaper methods for studying these microbes have become available recently, their importance to our health has grown increasingly evident. Scientists now suspect that our microbial communities contribute to a number of diseases, from allergic disorders like asthma and hay fever, to inflammatory conditions like Crohn's disease, to cancer, heart disease, and obesity.

We are, numerically speaking, 10 percent human, and 90 percent microbe. 

As newborns, we encounter our first microbes as we pass through the birth canal. Until that moment, we are 100 percent human. Thereafter, we are, numerically speaking, 10 percent human, and 90 percent microbe. Our microbiome contains at least 150 times more genes, collectively, than our human genome. Think of it as a hulking instruction manual compared to a single page to-do list.

As we mature, we pick up more microbes from breast milk, food, water, animals, soil, and other people. Sometime in childhood, the bustling community of between 500 and 1,000 species stabilizes. Some species are native only to humans, and may have been passed down within the family like heirlooms. Others are generalists—maybe they've hopped aboard from pets, livestock, and other animal sources.

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