Katya Gavrish is searching for new brain drugs in a seemingly unlikely place: human stool samples. An earnest and focused microbiologist who trained in Russia and loves classical music, she’s standing in front of a large anaerobic chamber in a lab at Holobiome, a small startup company in Cambridge, Massachusetts. She reaches into the glass-fronted chamber through Michelin Man–like sleeves to begin to dilute the sample inside. That’s the first step toward isolating and culturing bacteria that Gavrish and her Holobiome colleagues hope will produce new treatments for depression and other disorders of the brain and nervous system.
The eight-person company plans to capitalize on growing evidence from epidemiological and animal studies that link gut bacteria to conditions as diverse as autism, anxiety, and Alzheimer’s disease. Since its founding a mere 5 years ago, Holobiome has created one of the world’s largest collections of human gut microbes. The company’s CEO, Phil Strandwitz, cannot yet say exactly what form the new treatments will take. But the targeted ailments include depression and insomnia, as well as constipation, and visceral pain like that typical of irritable bowel syndrome—conditions that may have neurological as well as intestinal components. Strandwitz, a mild-mannered Midwesterner with a Ph.D. in microbiology, isn’t prone to visionary statements, but neither is he short on ambition: He predicts the first human trial will start within 1 year.
The allure is simple: Drug development for neuropsychiatric disorders has lagged for decades, and many existing drugs don’t work for all patients and cause unwanted side effects. A growing number of researchers see a promising alternative in microbe-based treatments, or “psychobiotics,” a term coined by neuropharmacologist John Cryan and psychiatrist Ted Dinan, both at University College Cork. “This is a really young and really exciting field with a huge amount of potential,” says Natalia Palacios, an epidemiologist at the University of Massachusetts, Lowell, who is looking into connections between gut microbes and Parkinson’s disease.
Some researchers prefer a less hurried approach focused on understanding the underlying biology. But Holobiome and a few other companies are eager to cash in on the burgeoning, multibillion-dollar market that has already sprung up for other microbial therapies, which aim to treat conditions including intestinal disorders allergies, and obesity. Those companies are pushing ahead despite many unresolved questions about how psychobiotic therapies might actually work and the potential dangers of moving too fast. “There’s a gold rush mentality,” says Rob Knight, a microbiologist at the University of California (UC), San Diego.
Over the past 20 years, the recognition that the microbes living inside us outnumber our body’s own cells has turned our view of ourselves inside out. The gut microbiome, as it’s known, weighs about 2 kilograms—more than the 1.4-kilogram human brain—and may have just as much influence over our bodies. Thousands of species of microbes (not only bacteria but also viruses, fungi, and archaea) reside in the gut. And with as many as 20 million genes among them, those microbes pack a genomic punch that our measly 20,000 genes can’t match. Gut bacteria can make and use nutrients and other molecules in ways the human body can’t—a tantalizing source of new therapies.
The brain is the newest frontier, but it’s one with an old connection to the gut. The ancient Greeks, for example, believed mental disorders arose when the digestive tract produced too much black bile. And long before microbes were discovered, some philosophers and physicians argued that the brain and gut were partners in shaping human behavior. “What probably happens is that our brain and our gut are in constant communication,” says Cryan, who over the past decade has helped drive efforts to decode those communications. [Continue reading…]