Zoobiquity (25 page)

I’d long known that antibiotics are used in farming to stop the spread of certain diseases, especially under cramped and stressful living conditions. But antibiotics don’t kill just the bugs that make animals sick. They also decimate beneficial gut flora. And these drugs are routinely administered even when infection is not a concern. The reason may surprise you. Simply by giving antibiotics, farmers can fatten their animals
using less feed
. The scientific jury is still out on exactly why these antibiotics promote fattening, but a plausible hypothesis is that by changing the animals’ gut microflora, antibiotics create an intestine dominated by colonies of microbes that are calorie-extraction experts. This may be why antibiotics act to fatten not just cattle, with their multistomached digestive systems, but also pigs and chickens, whose GI tracts are more similar to ours.

This is a really key point: antibiotic use can change the weight of farm animals. It’s possible that something similar occurs in other animals—namely, us. Anything that alters gut flora, including but not limited to antibiotics, has implications not only for body weight but for other elements of our metabolism, such as glucose intolerance, insulin resistance, and abnormal cholesterol. And don’t forget the trillions of creatures making up our microbiomes are constantly interacting in complex ways with one another. They have oscillators that respond to circadian rhythms. The dynamic population of that tiny, contained universe exerts more influence over metabolism than physicians have ever suspected.

When the Firmicutes/Bacteroidetes study appeared in
Nature
, it sparked an interest in other obesity risk factors that are less obviously under our control than diet and exercise. Blogs were soon buzzing about a different study showing that having a fat friend increases a person’s chance of becoming overweight himself.
The Harvard medical sociologist Nicholas Christakis and U.C. San Diego scientist James Fowler were describing a “contagion” of social habits and practices. Your fat friend’s bad food choices and exercising habits could influence your own willpower and attitude toward food. Christakis and Fowler were quick to explain that the finding was not literal but symbolic. You couldn’t catch the “fat flu” from an ill-aimed sneeze in the waiting room of a lap band clinic. Rather, what was “infectious” was other people’s attitudes toward eating.

But when I studied the animal literature, I learned that infectious obesity may not be solely metaphorical. According to some experts, it is altogether literal and real. Nikhil Dhurandhar, a nutrition and food scientist at Wayne State University, in Detroit, explains: “
It has been proven that animals became obese when infected with certain viruses.” He calls it “infectobesity.” Dhurandhar reports that seven viruses and a prion have been linked with obesity in animals as varied as chickens, horses, lions, and rats. That’s right: infectious weight gain, spread or facilitated by microscopic pathogens.

On the hottest days between mid-May and late August, alongside one of the many ponds around State College, Pennsylvania, chances are good you’ll spy a tall, thin biologist creeping through the cattails in khaki shorts and a battered cap. He’ll be crouched, moving in barely perceptible super slo-mo. Suddenly, with an expert forehand swing, he’ll swipe a wood-handled net through a stand of reeds or bulrushes. (The move, he explains, is similar to a lacrosse catch or a tennis stroke, which is why he likes to hire grad students who’ve played these sports before.) Nipping the mesh shut with his free hand, he’ll peek inside to see if he captured his quarry:
Libellula pulchella
, the twelve-spotted skimmer dragonfly.

James Marden is an entomologist and professor of biology at Penn State University. For more than two decades at ponds in central Pennsylvania
he has studied the flight mechanics of dragonfly wings. He told me that these insects are among the fittest animals on Earth, extraordinarily lean and muscular. Over 300 million years, dragonflies have evolved so perfectly to the acrobatic demands of hovering, bobbing, and looping the loop that Marden calls them “world-class, elite animal athletes.”

Usually dragonflies are pugnacious and extremely territorial, always up for a skirmish with another male. When two meet, they zoom at each other in belligerent, balletic aerial combat that ends with the loser being chased off. Some males, however, loiter on the outskirts of the action. Instead of spoiling for fights and flying straight into brawls, they “glide”—easing their way past challengers without coming to blows, as if to say, “I’m just passing through. No problem. Pay no attention to me. I was just leaving.”

In the early 2000s, intrigued by this behavior, and whether it might have something to do with muscle performance, Marden collected some of these slower, evasive dragonflies. And when he got them back to his lab, he discovered something shocking. Although on the outside the dragonflies looked perfectly normal—lean and combat ready—Marden’s examination showed that they were actually very, very sick. But their disease was peculiar for these “jet fighters of the insect world.” They were all medically obese.

Fat was collecting in their body tissues instead of converting into energy to fuel their extraordinary wing muscles. Their blood sugar
^a
concentrations were double that of healthy dragonflies, putting them in an insulin resistant–like state—similar to what’s seen in human patients with type 2 diabetes. They were slow, weak, sluggish, and unable to fight for females or defend territory.

That a wild dragonfly could develop a form of
metabolic syndrome
^b
has the potential to revise thinking about human weight gain and maybe even the obesity epidemic itself.
When Marden looked inside the dragonflies’ guts, he found something that surprised him. Freckling their
intestines were large white parasites. Some of them were so big—up to one-fiftieth of an inch—that Marden could see them without a microscope. Magnified, they looked mild-mannered enough: like plump little grains of rice.

What the parasites caused in the dragonflies, however, was anything but mild. They were gregarines, protozoans from the family that causes malaria and cryptosporidiosis in humans. In the dragonflies they triggered an inflammatory response that interfered with the insects’ ability to metabolize fat. That’s why it was collecting in their body tissues, particularly around their muscles. Their fat deposits were reducing their muscle performance, causing the dragonflies to relinquish territory and abandon mating opportunities.

By measuring the way the dragonflies’ muscles exchanged oxygen and carbon dioxide, Marden and his graduate student Rudolf Schilder could see that the infection was directly causing these changes. He told me it wasn’t just that the dragonflies were weakened by the presence of the parasites, making them duller and slower. Rather, “
specific components of their metabolism had changed.”

The gregarine infections also caused chronic activation of a signaling molecule involved in immune and stress responses, called p38 MAP kinase. In humans, the same molecule is implicated in insulin resistance that can lead to type 2 diabetes.

Intriguingly, the parasites were noninvasive, meaning they didn’t chew into or visibly damage the gut walls. Their inflammatory effect seemed to be triggered by substances they secreted and excreted. Eerily, the blood sugars of uninfected dragonflies became abnormal after they simply
drank water
containing trace amounts of the gregarines’ excretions or secretions.

At first, the possibility that obesity has an infectious component seemed ludicrous to me. Having been steeped in the simple diet-and-exercise, calories-in, calories-out approach, and knowing that reducing intake and increasing activity does result in at least temporary weight loss, I thought that infectobesity seemed unexpected and, frankly, even unlikely.

But although I had never heard about it, the search for infectious pathogens that promote weight gain has been under way since at least 1965, when a microbiologist at the State University of New York, Syracuse, explored how a certain worm caused mice and hamsters to become
obese. He suggested that the worms might be “leaking” a hormone into the bloodstreams of the rodents, causing them to eat more in order to satisfy the chemistry of the parasite.

And, indeed, infections of many kinds influence appetite. Tapeworms make you hungry. Certain viruses put you off your feed. In fact, appetite is one of the first things doctors ask patients about when we’re taking a medical history, because it’s one of the most sensitive markers of infection. These facts made me consider more seriously the real possibility that microbial invaders might manipulate what, how, and when we eat.

It wasn’t that long ago that a serious human intestinal medical condition was unexpectedly found to have an infectious component. For decades, gastric ulcers were believed to occur as a result of our stressed lives and overly reactive psyches. You got them, the medical wisdom went, if you were anxious and couldn’t resist greasy, spicy foods.
In 2005, the Australians Barry Marshall and J. Robin Warren, a physician and a pathologist, won the Nobel Prize in Medicine for busting that myth. They identified the cause of many ulcers as
Helicobacter pylori
, a contagious bacterium easily treated with a dose of antibiotics.
The road to the Nobel was long, however. For years Marshall and Warren had to endure criticism, rejection, and scorn. But now the microbiome is being examined for organisms that may be responsible for irritable bowel syndrome and Crohn’s disease. Maybe obesity should be next.

But the research on infectious causes of metabolic syndromes is still at the stage where nutrition scientists and doctors dismiss it—or at least don’t seem quite ready to hear it. Marden published his research in a top academic journal, the
Proceedings of the National Academy of Sciences
, and wrote an opinion piece for a human diabetes journal. Yet he told me there “
really wasn’t much response. I don’t think the medical community was swayed by our results or super eager to hear about it. It’s been pretty much a ‘so what?’ from the medical community.”

Whether infection will ultimately be proven to play a part in human obesity is still hard to say. However, a cross-disciplinary, zoobiquitous approach—one that connects the knowledge of a dragonfly expert in an agricultural sciences biology department with researchers looking at human obesity—may spark innovative hypotheses and a broadened view of this major health threat. We live in a world teeming with organisms
in us, on us, and around us. Our defenses against them drive many of our diseases. It’s critically important that researchers charged with understanding and containing obesity’s dangerous growth remain open to ecological factors, including lightness, darkness, seasonal shifts, and, yes, even infectious organisms. As Marden put it when his paper came out in 2006, “
Metabolic disease isn’t some strange thing having just to do with humans. Animals in general suffer from these symptoms … [and] it would be irresponsible for us not to point out these possibilities.”

To repeat: “Obesity is a disease of the environment.” And while Big Gulps and Segways play a primary role, so, too, do these much larger and much smaller forces. An expanded, environmental approach to weight has already cured two obese patients from the Chicago area—those two obese grizzly bears at the Brookfield Zoo.

Whether it was circadian rhythms, imbalanced microbiomes, seasonally confused intestines, an infectious parasite, or just access to too much food that caused Axhi and Jim to pack on the pounds over the years is hard to say. But their pattern of fattening before Watts changed what, when, where, how, and how much they ate resembles our own.

Watts had decided to make a massive change that was both innovative and as old as eating itself. She would approximate the yearly rhythms of a wild diet. In other words, she would let the seasons and the bears’ bodies lead the way.

She started with
what
they ate. For years, their food had been abundant, readily available, and largely unchanging throughout the year. It included processed dog food, bread from a local bakery, supermarket apples and oranges, and ground beef. Gradually, Watts challenged the bears’ taste buds. She swapped out a serving of lettuce and introduced kale. She traded mango for apple. Then spinach, celery, peppers, and tomatoes subbed in for sweet potatoes and oranges. Although this produce wasn’t exactly identical to what they’d find growing on the banks of an Alaskan river, in terms of nutrient range, variety, and seasonality, it was an improvement.

Soon, when the keepers showed up with a meal, the bears were as enthusiastic as human foodies sniffing out the exotic offerings at a new gastropub. Watts also added whole prey like fish, rats, and rabbits, and timed their appearance on the menu with when those foods would be
found in the wild. She also ordered boxes of wax worms, which she dumped in the bears’ foraging pile—a big, peaty dirt mound—and let them rummage and eat to their hearts’ content. With each of these dietary introductions the bears consumed not only new sources of protein and vitamins at seasonally appropriate times of the year, but whatever new and varied microorganisms happened to be making those food items their home. Although she notes this wasn’t at first intentional, Watts was following her own motto: “feeding the bugs” in their GI tracts.

Watts also decided to allow the bears to enter a more seasonally appropriate winter torpor. It wasn’t a full hibernation (which many bears in the wild don’t do anyway). But it was a big change for Axhi and Jim. For the previous decade, the bears had been awakened every day throughout winter for feeding. Sometimes the keepers had to rouse them by shouting or making loud clanging noises. Watts instructed that the bears be allowed to sleep through the winter months. And she ordered that, if they woke, they not be presented with food around the clock but be given “one shot” at a small amount before it was removed. On the surface, this plan would seem to work in favor of weight loss because it reduced the number of overall calories the bears consumed. But its efficacy may have been deeper than that. Sleep and metabolism are interconnected, and the longer periods of fasting may have signaled other physiologic changes to the bears’ bodies, such as intestinal lengthening or shortening.