The trillions of bacteria in and on our bodies can bolster our health and contribute to disease, but just which microbes are the key actors has been elusive. Now, a study involving thousands of people in Finland has identified a potential microbial culprit in some cases of depression.
The finding, which emerged from a study of how genetics and diet affect the microbiome, “is really solid proof that this association could have major clinical importance,” says Jack Gilbert, a microbial ecologist at the University of California, San Diego, who was not involved with the work.
Researchers are finding ever more links between brain conditions and gut microbes. People with autism and mood disorders, for example, have deficits of certain key bacteria in their guts. Whether those microbial deficits actually help cause the disorders is unclear, but the findings have spawned a rush to harness gut microbes and the substances they produce as possible treatments for a variety of brain disorders. Indeed, researchers recently reported in Frontiers in Psychiatry that fecal transplants improved symptoms in two depressed patients.
Guillaume Méric didn’t set out to find microbes that cause depression. A microbial bioinformatician at the Baker Heart & Diabetes Institute, he and his colleagues were analyzing data from a large health and lifestyle study from Finland. Part of a 40-year effort to track down underlying causes of chronic disease in Finnish people, the 2002 study assessed the genetic makeup of 6000 participants, identified their gut microbes, and compiled extensive data about their diets, lifestyles, prescription drug use, and health. Researchers tracked the health of participants until 2018.
Méric and his colleagues combed the data for clues to how a person’s diet and genetics affect the microbiome. “There have been very few studies that have examined [all these factors] in such detail,” Gilbert says. Two sections of the human genome seemed to strongly influence which microbes are present in the gut, the researchers report this week in Nature Genetics. One contains the gene for digesting the milk sugar lactose, and the other helps specify blood type. (A second study, also published today in Nature Genetics, identified the same genetic loci by analyzing the relationship between the genomes and gut microbes of 7700 people in the Netherlands.)
Méric’s team also explored which genetic variants might affect the abundance of certain microbes—and which of those variants were linked to 46 common diseases. When it came to depression, two bacteria that cause infections in hospitalized patients, Morganella and Klebsiella, seemed to play a causal role, the researchers say. One of them, Morganella, was significantly increased in a microbial survey of the 181 people in the study who later developed depression.
“This is really exciting,” says Jeroen Raes, a microbiologist at KU Leuven who was not involved with the study. “The beauty of the work,” he adds, is that Méric and colleagues made the connection between increased levels of the bacterium and patients undergoing depression.
Morganella has already been implicated in depression. As far back as 2008, researchers investigating a possible link between depression and inflammation found depressed people had stronger immune responses to chemicals produced by Morganella and other gram-negative bacteria in the gut. Thus, the newest study seems to be “further proof” that inflammation caused by gut microbes can influence mood, Gilbert says.
But the field is still in its infancy, says Gerard Clarke, a microbiome researcher at University College Cork, as there are many forms of depression and many possible ways that microbes could affect this disease. The “holy grail” is to identify a missing microbe that could be given as supplement, he says. But it’s less clear how Morganella could be eliminated from the gut to relieve symptoms. “That’s a bit more challenging.”