Doctors and psychiatrists have long suspected that diet can alter a person’s temperament, and studies over the past decade have turned those suspicions into hard data. It now seems clear that a healthy diet can lower the risk of depression and other mental disorders. What is also clear is that some of that effect may be tied to bacteria and other residents of the digestive tract. “These bacteria are little factories producing all sorts of chemicals,” says John Cryan, a professor of anatomy and neuroscience at University College Cork in Ireland. Cryan and others are trying to sort out what materials might be most useful in boosting mood with the hopes of someday concocting a “psychobiotic”—an infusion of microbes that works as one of the “New Tools for Depression” (Spring 2018).

That gut microbes play some role in mood has been boosted by recent research. In a 2019 article in Nature Microbiology, a team of European researchers surveyed the gut bacteria in more than 2,100 people through genomic screening. They identified two genera of bacteria—Coprococcus and Dialister—that were sparse in people with depression. The study also found that Coprococcus and another bacterium, Faecalibacterium, were especially abundant in people who reported a high quality of life.

Study co-author Jeroen Raes, a microbial immunologist at VIB-KU Leuven in Belgium, notes that both Coprococcus and Faecalibacterium can produce butyrate, an anti-inflammatory compound. The study doesn’t prove any cause and effect, but the possibility is intriguing to those who have long suspected that an inflammatory response plays a role in mood disorders. “It’s tempting to think that inflammation in the gut could be related to inflammation in the brain, which could in turn be related to depression,” he says. Raes and his colleagues also showed that many gut bacteria have the genetic capacity to either produce or metabolize neuroactive compounds such as dopamine and serotonin.

Teasing out which bacteria are particularly helpful might guide future clinical trials of probiotics, although “that part of the field needs to catch up,” says Cryan. He and colleagues identified 20 such clinical trials in a January 2020 issue of the Harvard Review of Psychiatry, but the studies used widely varying designs that made it hard to draw generalized conclusions.

Cryan points to one Iranian double-blind, placebo-controlled study. As reported in Clinical Nutrition in 2019, depressed individuals who took a probiotic capsule containing strains of Lactobacillus helveticus and Bifidobacterium longum for eight weeks showed improvement in depression symptoms compared with a placebo.

Probiotics aren’t the only way the microbiome can be enlisted to improve mental health. Valerie Taylor, a psychiatrist at the University of Calgary in Canada, is actively studying a more direct approach: fecal transplants from healthy volunteers. She’s currently recruiting patients with bipolar disorder, and is about to start a study of people with major depression. “The premise of a fecal transplant is you’re trying to reset the microbiome of someone who is unwell,” she says. The studies will track any improvement in symptoms as well as any changes in the microbial community.

A fecal transplant—an entire colony of microbes taken from a healthy donor—may be a blunt approach, and not without its own dangers, but the insights could help lead the way to psychobiotic capsules and other interventions, Taylor says. “Right now, we don’t even know what normal looks like, and we don’t know what abnormal looks like,” she says. “We’re trying to find the things that we need to target.”

Cryan is studying the possibility of using diet to create a depression-resistant gut microbiome. He’s partly inspired by a 2017 study showing that a 12-week Mediterranean-style diet reduced symptoms of major depression. “I fervently believe that the beneficial effects of that trial are because of the microbiome,” he says. He has started a pilot study to see whether a similar diet—ramped up with extra fiber and bacteria-rich fermented products—could alter the gut bacteria community and ease feelings of stress and depression. “We’re very excited about developing a psychobiotic diet,” he says.

The potential of a bacterial remedy for depression has grown stronger but Cryan says it will take more studies to win over the doubters. “I see a long way to go toward convincing a very conservative medical community,” he says.