Bioessays Gut Bacteria And Anxiety

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Consider this: Right now, as you're sitting there, there's a battle raging in your belly. Some 1,000 species of bacteria are duking it out, trying to establish dominance. Why should you care? Because whether the good bacteria in your gut or the bad triumph doesn't just decide how well you digest your dinner, respond to allergens and fend off diseases—it also helps determine how much weight you're likely to gain. Or lose.

"Simply put, if you get the microbiome—that collection of bacteria inside you—healthy, you will lose weight," says Raphael Kellman, MD, a New York City physician and author of The Microbiome Diet. "It's less about eating a certain percentage of carbohydrates, protein and fat than about correcting the overgrowth of unhealthy bacteria, which is making you crave the wrong foods, triggering inflammation."

A flurry of ground-breaking findings are helping to connect the dots about how our gut bacteria may shape our, well, shape. In a study in the British Journal of Nutrition, obese women who took a probiotic supplement (of the bacteria Lactobacillus rhamnosus) lost twice as much weight and fat over about six months—and were better at keeping it off—as those who took a placebo. Probiotics may have helped by controlling the women's appetites, which seem to have waned as their microbiomes changed.

Unhealthy gut bacteria also produce food cravings: A study published in BioEssays suggests that some microbes may drive us to eat doughnuts or another tempting treat. These gut bugs send chemical messages to the brain that sway our appetite and mood—perhaps making us feel anxious until we gobble a square of dark chocolate or a T-bone steak.

Fortunately, we can begin to take control by feeding our microbiome the right foods. "I tell my patients, 'The bacteria follow the food,'" says gastroenterologist Robynne Chutkan, MD, founder of the Digestive Center for Women in Chevy Chase, Md., and author of Gutbliss. "What we eat dictates the kind of bacteria we grow in our gut garden."

This is big news: There are trillions of microbes in your belly that will—if you feed them well—help you fight flab and win.

Gut check #1: Get Your Two P's
Basically, it all begins with probiotics and prebiotics, components of food believed to play an important role in improving gut health. Probiotics are a type of good bacteria, similar to the ones that already reside in your gut. Ingesting these organisms aids digestion and helps change and repopulate intestinal bacteria to balance what doctors refer to as "gut flora." Prebiotics are plant-fiber compounds, also found in food, that pass undigested through the upper part of the gastrointestinal tract and help stimulate the growth of good bacteria. When pre- and probiotics are combined, they become an intestinal power couple (or, in blunter terms, they kick nutritional butt).

RELATED:4 Surprising Health Benefits of Yogurt

Gut check #2: Go Live
Fermented foods deliver probiotics directly to the gut. A cup of yogurt a day? It's a nice start. Look for products that say "live and active cultures" on the label, and be careful when it comes to fruit-infused flavors: Some are loaded with sugar, which can feed bad bugs, so be sure to check the ingredients and aim for fewer than 15 grams per serving. For even more probiotics, try Greek yogurt or kefir, a tangy dairy drink that's packed with good bugs. A 2011 Harvard study found that yogurt was more strongly linked to weight loss than any other health food. In fact, people who ate an extra serving a day lost nearly a pound every four years.

Next Page: Gut check #3: Down Some Fiber

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Gut check #3: Down Some Fiber
It does more than fill you up: Research shows that foods that are high in fiber help promote the growth of friendly bacteria. Case in point: In a University of Illinois study, people who ate high-fiber snack bars experienced a growth of anti-inflammatory bacteria in their bellies.

RELATED:20 Best Foods for Fiber

Gut check #4: Mix Up Your Menu
Eat an assortment of foods to encourage a more varied metropolis in your belly. Recent studies suggest that the intestines of lean people look more like bustling cities than sleepy towns. (Translation: They're densely populated and diverse.) One study showed that individuals who had a healthy weight, body mass index, waist circumference and blood sugar level were more apt to have high levels of three different types of bacteria—Firmicutes, Bifidobacteria and Clostridium leptum. What's more, in a pair of French studies, people with diverse gut microbiomes were less likely to be obese or at risk of diabetes. Plus, their intestinal ecosystems were home to fewer pro-inflammatory bacteria. It's easy to change up your meals: If you had salad with grilled chicken yesterday, for example, go with a fish taco or a tofu stir-fry today.

Gut check #5: Skip Bad-News Foods
What you don't eat is every bit as crucial as what you do add to your diet. Keep your gut flora fit by cutting back on these offenders.

Refined carbs
Fatty and sugary foods not only tend to lack fiber—which is ideal food for the microbiome—but can also cause bad bacteria to thrive. And let's face it: If you're pounding that bag of potato chips, chances are you're not munching on celery sticks, blueberries and other gut-friendly eats.

Animal protein
A diet heavy in fat and protein (such as meat and cheese) feeds a type of bacteria, Bilophilia, that has been linked to inflammation. Lawrence David, PhD, assistant professor at Duke University's Institute for Genome Sciences and Policy, saw the levels of this bacteria shoot up in study participants scarfing ribs and brisket, but not in those eating squash and lentils. Dr. Kellman suggests limiting red meat to once a week. It's smart for your heart—and hips!

‘‘Dr. Lyte,’’ he later asked at a question-and-answer session, ‘‘if what you’re saying is right, then why is it when we give antibiotics to patients to kill bacteria, they are not running around crazy on the wards?’’

Lyte knew it was a dismissive question. And when he lost out on the grant, it confirmed to him that the scientific community was still unwilling to imagine that any part of our neural circuitry could be influenced by single-celled organisms. Lyte published his theory in Medical Hypotheses, a low-ranking journal that served as a forum for unconventional ideas. The response, predictably, was underwhelming. ‘‘I had people call me crazy,’’ he said.

But by 2011 — when he published a second theory paper in Bioessays, proposing that probiotic bacteria could be tailored to treat specific psychological diseases — the scientific community had become much more receptive to the idea. A Canadian team, led by Stephen Collins, had demonstrated that antibiotics could be linked to less cautious behavior in mice, and only a few months before Lyte, Sven Pettersson, a microbiologist at the Karolinska Institute in Stockholm, published a landmark paper in Proceedings of the National Academy of Science that showed that mice raised without microbes spent far more time running around outside than healthy mice in a control group; without the microbes, the mice showed less apparent anxiety and were more daring. In Ireland, Cryan published his forced-swim-test study on psychobiotics. There was now a groundswell of new research. In short order, an implausible idea had become a hypothesis in need of serious validation.

Late last year, Sarkis Mazmanian, a microbiologist at the California Institute of Technology, gave a presentation at the Society for Neuroscience, ‘‘Gut Microbes and the Brain: Paradigm Shift in Neuroscience.’’ Someone had inadvertently dropped a question mark from the end, so the speculation appeared to be a definitive statement of fact. But if anyone has a chance of delivering on that promise, it’s Mazmanian, whose research has moved beyond the basic neurochemicals to focus on a broader class of molecules called metabolites: small, equally druglike chemicals that are produced by micro-organisms. Using high-powered computational tools, he also hopes to move beyond the suggestive correlations that have typified psychobiotic research to date, and instead make decisive discoveries about the mechanisms by which microbes affect brain function.

Two years ago, Mazmanian published a study in the journal Cell with Elaine Hsiao, then a graduate student and now a neuroscientist at Caltech, and others, that made a provocative link between a single molecule and behavior. Their research found that mice exhibiting abnormal communication and repetitive behaviors, like obsessively burying marbles, were mollified when they were given one of two strains of the bacterium Bacteroides fragilis.

The study added to a working hypothesis in the field that microbes don’t just affect the permeability of the barrier around the brain but also influence the intestinal lining, which normally prevents certain bacteria from leaking out and others from getting in. When the intestinal barrier was compromised in his model, normally ‘‘beneficial’’ bacteria and the toxins they produce seeped into the bloodstream and raised the possibility they could slip past the blood-brain barrier. As one of his colleagues, Michael Fischbach, a microbiologist at the University of California, San Francisco, said: ‘‘The scientific community has a way of remaining skeptical until every last arrow has been drawn, until the entire picture is colored in. Other scientists drew the pencil outlines, and Sarkis is filling in a lot of the color.’’

Mazmanian knew the results offered only a provisional explanation for why restrictive diets and antibacterial treatments seemed to help some children with autism: Altering the microbial composition might be changing the permeability of the intestine. ‘‘The larger concept is, and this is pure speculation: Is a disease like autism really a disease of the brain or maybe a disease of the gut or some other aspect of physiology?’’ Mazmanian said. For any disease in which such a link could be proved, he saw a future in drugs derived from these small molecules found inside microbes. (A company he co-founded, Symbiotix Biotherapies, is developing a complex sugar called PSA, which is associated with Bacteroides fragilis, into treatments for intestinal disease and multiple sclerosis.) In his view, the prescriptive solutions probably involve more than increasing our exposure to environmental microbes in soil, dogs or even fermented foods; he believed there were wholesale failures in the way we shared our microbes and inoculated children with these bacteria. So far, though, the only conclusion he could draw was that disorders once thought to be conditions of the brain might be symptoms of microbial disruptions, and it was the careful defining of these disruptions that promised to be helpful in the coming decades.

The list of potential treatments incubating in labs around the world is startling. Several international groups have found that psychobiotics had subtle yet perceptible effects in healthy volunteers in a battery of brain-scanning and psychological tests. Another team in Arizona recently finished an open trial on fecal transplants in children with autism. (Simultaneously, at least two offshore clinics, in Australia and England, began offering fecal microbiota treatments to treat neurological disorders, like multiple sclerosis.) Mazmanian, however, cautions that this research is still in its infancy. ‘‘We’ve reached the stage where there’s a lot of, you know, ‘The microbiome is the cure for everything,’ ’’ he said. ‘‘I have a vested interest if it does. But I’d be shocked if it did.’’

Lyte issues the same caveat. ‘‘People are obviously desperate for solutions,’’ Lyte said when I visited him in Abilene. (He has since moved to Iowa State’s College of Veterinary Medicine.) ‘‘My main fear is the hype is running ahead of the science.’’ He knew that parents emailing him for answers meant they had exhausted every option offered by modern medicine. ‘‘It’s the Wild West out there,’’ he said. ‘‘You can go online and buy any amount of probiotics for any number of conditions now, and my paper is one of those cited. I never said go out and take probiotics.’’ He added, ‘‘We really need a lot more research done before we actually have people trying therapies out.’’

If the idea of psychobiotics had now, in some ways, eclipsed him, it was nevertheless a curious kind of affirmation, even redemption: an old-school microbiologist thrust into the midst of one of the most promising aspects of neuroscience. At the moment, he had a rough map in his head and a freezer full of monkey fecals that might translate, somehow, into telling differences between gregarious or shy monkeys later in life. I asked him if what amounted to a personality transplant still sounded a bit far-fetched. He seemed no closer to unlocking exactly what brain functions could be traced to the same organ that produced feces. ‘‘If you transfer the microbiota from one animal to another, you can transfer the behavior,’’ Lyte said. ‘‘What we’re trying to understand are the mechanisms by which the microbiota can influence the brain and development. If you believe that, are you now out on the precipice? The answer is yes. Do I think it’s the future? I think it’s a long way away.’’

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Correction: July 12, 2015

An article on June 28 about microbiota and the brain described incorrectly the affiliation of Elaine Hsiao, an author of a study published in the journal Cell that linked bacteria to behavioral changes. At the time, she was a graduate student in the lab of Paul Patterson, another author of the study, not in the lab of Sarkis Mazmanian.

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