The notion that the state of our gut governs our state of mind dates back more than 100 years. Many 19th- and early 20th-century scientists believed that accumulating wastes in the colon triggered a state of “auto-intoxication,” whereby poisons emanating from the gut produced infections that were in turn linked with depression, anxiety and psychosis. Patients were treated with colonic purges and even bowel surgeries until these practices were dismissed as quackery.
The ongoing exploration of the human microbiome promises to bring the link between the gut and the brain into clearer focus. Scientists are increasingly convinced that the vast assemblage of microfauna in our intestines may have a major impact on our state of mind. The gut-brain axis seems to be bidirectional—the brain acts on gastrointestinal and immune functions that help to shape the gut’s microbial makeup, and gut microbes make neuroactive compounds, including neurotransmitters and metabolites that also act on the brain. These interactions could occur in various ways: microbial compounds communicate via the vagus nerve, which connects the brain and the digestive tract, and microbially derived metabolites interact with the immune system, which maintains its own communication with the brain. Sven Pettersson, a microbiologist at the Karolinska Institute in Stockholm, has recently shown that gut microbes help to control leakage through both the intestinal lining and the blood-brain barrier, which ordinarily protects the brain from potentially harmful agents.
Microbes may have their own evolutionary reasons for communicating with the brain. They need us to be social, says John Cryan, a neuroscientist at University College Cork in Ireland, so that they can spread through the human population. Cryan’s research shows that when bred in sterile conditions, germ-free mice lacking in intestinal microbes also lack an ability to recognize other mice with whom they interact. In other studies, disruptions of the microbiome induced mice behavior that mimics human anxiety, depression and even autism. In some cases, scientists restored more normal behavior by treating their test subjects with certain strains of benign bacteria. Nearly all the data so far are limited to mice, but Cryan believes the findings provide fertile ground for developing analogous compounds, which he calls psychobiotics, for humans. “That dietary treatments could be used as either adjunct or sole therapy for mood disorders is not beyond the realm of possibility,” he says.