Jeremy Appleton, a naturopathic physician who has researched the gut–brain axis, says our gut microbiome and its connection with our brain have a significant effect on every part of the body.

“Every system in the body seems to be influenced by the quality of our microbiome and also the quality of that interface where those bacteria reside in us,” he explains. “It’s definitely a symbiotic relationship that we have with them.”

The gut microbiome can alter the function of the enteric nervous system by activating stress pathways in the brain. The process can also happen in reverse.

Stress and depression can disrupt the gut’s microbiome through stress hormones, inflammation, and changes within the autonomic nervous system—which regulates involuntary processes in the body such as heart rate, blood pressure, respiration, and digestion. These changes can cause gut bacteria to release substances that can affect our eating behavior and mood.

Alternately, gut bacteria can increase stress responsiveness and increase the risk of depression.

According to the chapter mentioned above, animal studies have found that the gut microbiome is an important factor behind mood, pain, cognition, and obesity. It’s an interesting relationship that may provide important clues into various neuropsychiatric diseases including schizophrenia, autism, and affective disorders (such as depression and bipolar disorder).

All of this has an impact on our behavior, Appleton says.

According to Appleton, research into the gut–brain axis has exploded in the past 15 to 20 years; unfortunately, the “lessons learned” are rarely applied by most practitioners.

“In terms of depression, it’s something that we still in mainstream medicine, we just really aren’t looking at when we’re talking about moods,” he says. “We’re not looking at the health of their gut—it still hasn’t become intuitive for us.”

Appleton says that instead of just prescribing drugs or supplements to address depression, clinicians should look at dysbiosis and/or evaluate for leaky gut syndrome “as part of the standard operating procedure.”

A holistic approach to treating depression is the best approach, Appleton says. He says he wouldn’t tell a patient not to take an antidepressant; however, if medication is the only treatment, “you’re going to touch part of the problem, but you’re not going to treat the whole problem.”

Angelo Pezzote, who holds a doctorate in pharmacy and is a board-certified psychiatric pharmacist and clinical mental health counselor, marries the two professions with mind and body and works almost as a psychiatrist would.

Although Pezzote assists prescribers with medication recommendations, his focus is less on medications and more on “nutritional psychiatry”—he works with clients to replenish and enhance the gut microbiome through methods such as lifestyle changes, stress reduction, exercise, and healthy eating.

Pezzote says that while some people do need medication, many may be overmedicated or rely on medication as their “one and only answer” for depression.

“I think for a lot of patients, they’re just used to ‘here, take this pill and you’re going to feel happy’ and that’s just not the way reality is. A lot of people on their antidepressants still feel sad and they need more than just a pill.”

Appleton agrees.

Managing stress is a major component of healing the gut. Pezzote says that stress “throws off” the immune system, causing inflammation, which is linked to depression and other mood disorders. Through managing stress, you can manage stress hormones that influence the gut microbiome.

“It’s really stress that gets people off balance,” Pezzote says.

Movement, meditation, yoga, tai chi, quality sleep, meaningful social interaction, having fun, and finding joy also can help manage stress and consequently help the gut.

Eating a plant-rich diet is very important in maintaining a healthy gut microbiome, given that the gut microbiome loves fiber and prebiotics—things we can’t digest.

Pezzote recommends a plant-rich diet, incorporating low-fat dairy, limiting processed meat and red meat, as well as refined sugar and flour, and increasing whole grains, healthy fats, and complex carbohydrates.

“If I had MDD or major anxiety disorder, I would be going top down and bottom up. It makes a lot of sense given the bidirectional nature of the gut-brain axis,” Appleton says.

Pezzote says healing the gut and treating depression cannot be solved with one intervention only.