Feeling Depressed? Bacteria in Your Gut May Be to Blame

In a series of studies, researchers are discovering that the microbial menagerie living in our digestive tract may help regulate brain function, including mental health. Recent findings by scientists in the U.S., Europe and China are linking our feelings of stress, anxiety and severe depression to disturbances among hundreds of microbe species living in our gut that some researchers have started calling the psychobiome.

Conversely, other bacteria in the gut appear to produce some of the same substances used by doctors to treat depression and may naturally play a role in maintaining our emotional balance.

“The feeling of malaise, if you will, is often associated with gastrointestinal disorders,” said microbiologist Jack Gilbert at the University of California, San Diego and the Scripps Institution of Oceanography, who helped pioneer the study of the human gut microbiome. It is “chemically altering nerve signals going into the brain, which alter brain chemistry and therefore behavior, mood and, we believe, depression and anxiety.”

As evidence, some scientists have been able to infect mice and rats with mental disorders, including depression and anxiety, by transplanting stool samples, which contain gut microbes, from human patients into laboratory animals, several recent studies show. “When you give these mice the microbes from depression, they begin to behave in a depressive-like way,” said psychiatrist

Julio Licinio

at State University of New York Upstate Medical University in Syracuse. These behavior changes in mice affect such things as appetite, weight gain and activities like swimming. Dr. Licinio studies the biology of depression and helped design some of the experiments. “It’s actually transmissible,” he said.

Until now, though, no one has been able to single out specific species of microbes linked to a mental illness. This month, an international research team for the first time identified dozens of species of gut microbes involved in depression by comparing patients diagnosed with the disorder to healthy people. These 47 species are a tiny fraction of the gut’s microbial diversity, which includes other single-celled organisms, thousands of virus species and fungi.

The new research by neuroscientist

Peng Xie

at China’s First Affiliated Hospital of Chongqing Medical University and colleagues reveals a potential mechanism for a mental illness that affects an estimated 350 million people world-wide, several experts said. The research was published in the journal Science Advances.

Scientists are rushing to discover how such microbes interact with the human central nervous system, what signals they send to the brain and how that alters a person’s behavior or risk of mental illness, in hopes of new treatments and diets for maladies of the mind.

“The big race is on to understand what role all these play in various brain diseases,” said

Emeran Mayer,

a medical psychologist at the University of California, Los Angeles who studies the brain and gut microbiome and has written “The Mind-Gut Connection.” He adds, “if you already have genetic risk factors for Parkinson’s disease or Alzheimer’s or major depression, this is a factor that could push it over the edge into a disease.”

Not so many years ago, the only microbes that attracted medical attention were germs that caused infections and diseases.

But indiscriminate use of antibiotics and other sanitation measures eliminated the harm that bacteria cause at the expense of the protection they can provide. Unintended health consequences ranged from increases in liver disease, Type 2 diabetes and asthma to preterm birth and antibiotic-associated diarrhea, according to a 2019 review in the Journal of Experimental Medicine and many other microbiology studies.

During the past decade, advances in low-cost, high-speed gene sequencing machines allowed researchers to study millions of microorganisms that normally can’t be grown in a laboratory. In these studies, researchers can determine whether genetic material belongs to bacteria though a biomarker called the 16s ribosomal RNA gene, which turns up only in microbes.

As a result, the study of the microbiome is one of the hottest new fields in medicine, with more than 15,000 scientific papers published last year alone. “There is a lot of excitement in the field of psychiatry now about this,” said

John Cryan

at the University College Cork in Ireland, who studies the microbiome and the neurobiology of stress.

Microbiologists calculate that the human gut contains more than 100 trillion microorganisms. Together they weigh about 5 pounds—about as much as a big mango and slightly more than the human brain, according to the European Society for Neurogastroenterology and Motility.

Moreover, where the human genome carries some 22,000 protein-coding genes, researchers estimate that the human microbiome contributes some eight million unique protein-coding genes, or 360 times more bacterial genes than human genes, according to the National Institutes of Health’s Human Microbiome Project.

These microbes appear especially adaptable to changes in the environment, diet and the biochemistry of emotion. While no one yet knows exactly why, patients with various psychiatric disorders including depression, bipolar disorder, schizophrenia and autism-spectrum disorder have significant disruptions in the composition of their gut microbiome.

The microbes appear to be in almost constant communication with the brain directly by affecting nerve signals and indirectly through chemicals absorbed into the bloodstream, said Dr. Gilbert, who also is scientific adviser for a small microbiome company called Holobiome in Cambridge, Mass., that seeks new ways to treat depression, insomnia and other ailments.

Some common gut bacteria, for example, help generate neurotransmitters such as serotonin, which affects neural activity related to mood and memory. It’s commonly used to treat depression. Others make an amino acid called gamma-aminobutyric acid that naturally blocks some brain signals. It’s used in medication to relieve anxiety and improve mood.

“The bacteria are hijacking parts of systems within the body that we know are affecting emotional regulation,” Dr. Cryan said. “This has led us to the idea that by targeting microbes in the gut, we can have behavioral effects that are going to have impact on overall well-being.”

Write to Robert Lee Hotz at lee.hotz@wsj.com