Mike, though, lives in Colorado, where he had read an article online about how Greenblatt had treated a young woman with severe obsessive-compulsive disorder using traditional psychotherapy and medication coupled, less traditionally, with probiotics — capsules filled with live “good” bacteria. Within six months, her symptoms were gone. Mike also had issues with anxiety — he’d started obsessively pulling his hair out 15 years earlier — but no one had been able to help him. Mike began treating himself by taking the strongest over-the-counter probiotics he could find and after a couple months, he noticed the urge to pull had disappeared. “IT WORKED!” Mike later wrote in a blog post.

“Thank you, you’ve never even met me and yet you’ve changed my life.” That was the sign-off in an e-mail from a man named Mike that arrived at the office of Dr. James Greenblatt, a psychiatrist and the chief medical officer of Walden Behavioral Care in Waltham, on July 24. Greenblatt is not unused to such effusive gratitude, but usually it comes from his patients.


The idea that microbes in the body can affect the brain has gone in and out of fashion. In 1896, physicians writing in Scientific American concluded, in the language of the day, that “certain forms of insanity” could be caused by infectious agents “similar to typhoid, diphtheria and others.” But after Freudian psychoanalysis became popular in the first half of the 20th century, the microbial theory of mental illness was largely forgotten, and stayed that way for decades.

Today, however, scientists know that trillions of micro-organisms live in your digestive system, where they outnumber your human cells many times over and may make up as much as 3 percent of your body weight. The evidence that these bacteria affect a dense network of neurons in your gut — often called the “second brain”— is vast and growing. In recent years, a microbial imbalance in the gut (called “dysbiosis”) has been associated with chronic fatigue, obesity, certain types of cancer, and other physical ailments.


It’s unclear exactly how or which bacteria cause or cure which disorders and in what complex ways, Greenblatt says, “but the research is quite clear that the GI tract affects brain health.” In this case, he says, “one plus one does equal two.”

Research on the microbiome got a kick-start with the emergence of new methods of DNA profiling that allowed doctors to quickly identify various species of bacteria. Now, studies exploring how gut flora may affect health are exploding onto the scene. Once considered “alternative” — maybe even a bit wacky — the field is becoming firmly entrenched in the medical establishment: In 2007, the National Institutes of Health earmarked $115 million for the first phase of the Human Microbiome Project, which brings together researchers from several institutions, including the Broad Institute in Cambridge, and aims to map the ecology of the gut. In late September, Harvard Medical School’s Division of Nutrition hosted a symposium in Boston called “Gut Microbiota, Probiotics and Their Impact Throughout the Lifespan.” It was so popular, there was a wait-list to get in.

Dr. James Greenblatt, chief medical officer of Walden Behavioral Care in Waltham, is a proponent of probiotics. Suzanne Kreiter/Globe staff

All the interest marks a fundamental change in the way scientists and medical professionals view the connection between the brain and the gut. Not that long ago, many doctors believed that the brain was essentially walled off from the rest of the body and protected from infection. “The dogma when I was in grad school was that nothing crosses the blood-brain barrier,” says Nancy Desmond, chief of the neuroendocrinology and neuroimmunology program at the National Institute of Mental Health. “But there are data now that punch holes in that dogma.” The challenge, she says, “is to try to get at the mechanisms that underlie this apparent communication between microbiota in the gut and brain function that is relevant to mental health.”


Possible pathways include the vagus nerve, which runs throughout the body, the spinal cord, and numerous immune and endocrine mechanisms. For example, a chemical in urine called HPHPA signals a buildup of dopamine in the brain, which in turn “strongly correlates with psychiatric symptoms,” according to Greenblatt, “from anxiety to agitation.” As in irritable bowel syndrome, the culprits here are species of the Clostridium bacteria. Fighting them with targeted antibiotics, along with high doses of probiotics, appears to help ease or eliminate symptoms.

Dr. Kyle Williams, director of the Pediatric Neuropsychiatry and Immunology Program at Massachusetts General Hospital, is also looking at how the microbiome influences the brain and behavior. But Williams cautions that the body’s ecosystem is incredibly complex and that the placebo effect — patients feeling better even if the treatment isn’t actually doing anything — can be very strong in psychiatry. “There’s a lot of excitement about the microbiome now,” he says, “but evidence is what helps us transform an exciting idea into therapies. It’s true the blood-brain barrier isn’t the impenetrable fortress we thought it was, but we’re learning more each day about how molecules traffic or are transported across it.”


Though much remains to be learned, many physicians and researchers believe there’s no harm in probiotics, as long as patients don’t forgo conventional medicines and treatments in their favor. “Whenever someone says there’s an impossibility in medicine,” says Williams, “they end up being corrected in a few years.”

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Elizabeth Gehrman is a frequent contributor to the Globe Magazine. Send comments to magazine@globe.com.