A link to depression might be in your gut bacteria

Understanding our stomach's microbiome could make doctors rethink how to treat depression.
a person in a gray shirt their hand over their stomach under dark lighting
Researchers are trying to get to the bottom of the gut's potential connection to depression. Deposit Photos

Of the trillions of microorganisms that call your gut home, 13 bacterial species may contribute to depression. A pair of studies published on December 6 in the journal Nature Communications identified bacteria linked to depression and a possible explanation for how they’re promoting depressive episodes. 

Depression is one of the leading causes of disability worldwide. About five percent of adults live with the condition. If left untreated, a depressive episode can significantly impair your life, from constant hopelessness to a loss of interest in day-to-day activities. Understanding just how these microbes contribute to our mental health could shape gut-driven approaches for managing the condition.

Certain gut bacteria could be causing a chemical imbalance in the brain 

In one of the studies, the authors examined the microbiome composition of 1,539 adults in the Netherlands. “Our biggest surprise was the strength of the relationship between gut bacteria and depression,” Robert Kraaij, a senior research scientist at Erasmus Medical Center Rotterdam in the Netherlands and study coauthor, wrote in an email to PopSci. Of the 13 microbial taxa linked to depression, people with a higher abundance of Sellimonas, Eggerthella, Lachnoclostridium, and Hungatella reported more depressive symptoms. 

The 13 microbial species help produce chemical messengers—glutamate, butyrate, serotonin, and gamma amino butyric acid (GABA)—which the levels are typically altered during the depression. The findings from the current study could help identify people who are most at risk for depression, explains Najaf Amin, a senior researcher at Oxford University and senior study author. 

In the future, Amin plans to study the levels of the four chemical messengers in the blood of people with and without depression to see how they compare. Doing so may help get a better sense of how gut bacteria influence a person’s brain chemistry and how the brain regulates mood.

[Related: Magic mushrooms help cancer patients deal with depression]

Differences across ethnicities in the gut microbiomes of people with depression

The second study investigated fecal samples of 3,211 individuals who resided in urban Amsterdam. The participants belonged to one of six different ethnic groups—Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan. The microbiome assessments showed changes in bacterial species associated with depressive symptoms, including those species from the Christensenellaceae, Lachnospiraceae, and Ruminococcaceae families. One interesting observation, however, was that not everyone with depression had the same amounts of each microbial species. About 18 to 29 percent of differences in depression-related bacteria was due to ethnic differences.

“This is pivotal research with interesting data on gut-brain [interactions], a burgeoning area of science and medicine now,” says Harvey Hamilton Allen Jr., chief gastroenterologist at Mohawk Valley Endoscopy Center at St. Luke’s Hospital, who was not involved in either of the studies.

What we know about the gut’s involvement in depression

One of the reasons depression is difficult to treat is that there seems to be no single cause. Prior research has linked depression to stressful or traumatic life events, while others have observed depression manifesting after chronic substance abuse. Genetic factors might also be at play, as people with a family history of depression are three times more likely to have it too. The gut microbiome might be another contributor at play. 

While the idea had been tossed around for centuries, biologists have only recently unearthed physical evidence of a gut-brain connection in the past couple of decades. The theory goes that humans have a “bidirectional” line of communication between the emotional and cognitive centers of the brain, explains Hamilton Allen Jr. Imagine a telephone wire running from your central brain to your enteric nervous system—a collection of neurons in the wall of the GI tract that controls your digestive system. The enteric nervous system is often called the “second brain” for its influence on the rest of the body. 

One important piece of evidence that the gut likely plays a role in depression is that about 95 percent of serotonin—often labeled the “happy hormone” for its mood-regulating effects—is made from gut bacteria. Paxil and Zoloft, two commonly prescribed medications for depression, block the body from reabsorbing serotonin to avoid the hormone’s levels from falling too low. 

Treating depression through the microbiome

A deep understanding of the ins and outs of the gut microbiome could revolutionize how we approach medicine, including how we treat depression. “If certain bacteria are part of the cause of depression, we can design treatments to modulate these bacteria,” says Kraaij.

One potential approach is through fecal transplants. While such a treatment might seem ripe for bacterial infections, it could help promote healthy gut bacteria in people who are unable to produce them on their own (there have been reported deaths from fecal transplants among immunocompromised people). Transporting the poop from a person with a healthy gut microbiota to someone with  an unhealthy gut has already become the standard of care for treating Clostridioides difficile infections. The procedure restores healthy bacteria back into the lower intestines. Just last week on December 2, the FDA approved the first pharmaceutical-grade fecal transplant to treat difficult intestinal infections.

[Related: Autism shapes the gut microbiome, scientists report, not the other way around]

There is also some growing evidence that fecal transplants could help with depression. In a small case study published in February 2022, two people with major depressive disorder underwent poop transplants in addition to their current treatment plan. Both showed a reduction in depressive-live behavior four weeks after the procedure. One of the patients continued to show improvement in their depressive symptoms for up to eight weeks after treatment, along with improvement in other GI problems. 

The two studies could make the fecal transplant process more efficient by knowing which of the 13 bacteria species need to be transferred to make the gut healthy again. What’s more, Hamilton Allen Jr. speculates the findings could even help fecal transplants to be more personalized to different ethnicities in the future. 

Still, gut microbes are one of many factors linked to depression, Hamilton Allen Jr. says. Without an experiment that could manipulate the microbiome to see how people fared with and without these microbes, scientists cannot definitively say a gut imbalance is a primary cause of depression. But he says, “this is definitely one of the new treatment modalities, and as we learn more about this organ, we are going to see more research going into treating the microbiome.”

Correction (December 12, 2022): This story has updated the genus name Clostridium difficile to Clostridioides difficile to reflect changes in taxonomic classification of the bacteria.