The Connection Between Your Gut and Your Mental Health

Back in the 1800s, one of the most hotly contested “celebrity” feuds was between two French chemists: Louis Pasteur and Antoine Béchamp. Chances are, you’ve only heard of one of these scientists, which means that he ostensibly “won” the debate. This is true, but it does not tell the full story, or even come close.

Pasteur and Béchamp were fighting about germs, also known as microbes or microorganisms. These tiny living things include viruses, bacteria, archaea, fungi, and protists — all too small to be seen by the naked eye. Both men agreed that these microbes existed. What they disagreed about was whether they were good or bad.

Pasteur believed microbes were bad. One of his signature contributions to public health was pasteurization, which kills microbes in milk and makes it safe to drink. Pasteur took this idea a step further, claiming that all microbes caused disease and that killing them was therefore always the cure. This became known as the germ theory of diseases, and today this framework informs much of modern medicine.

We now generally assume that killing off germs is the best way to prevent and cure disease, so we do it routinely. Just think about that hand sanitizer that you carry around with you, or the last round of antibiotics your doctor prescribed. And some specific bacteria, such as some E. coli and Salmonella, are pathogenic and therefore dangerous to us. But Pasteur’s germ theory was only partially correct. And Béchamp knew it.

To Béchamp, germs themselves were not strictly the problem. He believed they only caused disease when their environmental “terrain” was disrupted, making their host susceptible to disease. In other words, most microbes could only cause disease when the conditions in the body allowed them to overgrow.

Béchamp also believed that microbes were an essential part of human beings and all living things, so he viewed killing off germs as both impossible and terribly dangerous. Unfortunately, his argument failed to gain any traction. Pasteur was a brilliant public speaker, and in 1863 he allegedly gained Emperor Napoleon III’s undying support when he “proved” that wine went “bad” from bacterial contamination.

In vino veritas, as they say. But not always.

Thanks to recent research, we now know that it was Béchamp — not Pasteur — who had the better understanding of the microbial world.

Every day we discover new things about the sheer numbers of microbes living in and around us, not to mention the countless, complex ways they influence our health and behavior. Our bodies are host to multiple microbial communities — in our mouths, lungs, skin, and, most significantly, in our guts. Together, these are known as the “holobiome,” and they give us good reason to reconsider who and what we are as humans.

Are we lone creatures, or symbiotic communities made up of a combination of human and microbial cells? If you believe you are the former, I hope to change your mind.

 

Mental Health and the Gut

Not long after the debate between Pasteur and Béchamp, a Portuguese physician named Antonio Maria de Bettencourt Rodrigues became the first doctor we know of to make the connection between bacteria and mental health. In 1889, at a mental health congress in Paris, Rodrigues presented the idea that depression could be caused by “autointoxication,” a theory that bacterial waste products could build up in the body and cause disease. He treated depressed patients with a combination of dietary changes and gut detoxification.

The idea of autointoxication went hand in hand with Pasteur’s belief that all bacteria were harmful, and it became the prevailing theory of the day. Throughout the 19th century, autointoxication was widely viewed as a cause of or contributor to most diseases, leading to such interventions as colonic irrigation to clear out those bacterial waste products.

Rodrigues may have been the first to suggest autointoxication as a cause for depression, but some of his contemporaries also saw a potential connection between mental health and the gut. A scientist named François-André Chevalier-Lavaure observed that many of his psychiatric patients suffered from digestive conditions and saw improvements in their psychiatric symptoms after their digestive issues were treated.

Although the term “autointoxication” was imprecise and incorrect, these scientists were onto something. As the field of psychology grew over the course of the 20th century, the connection between gut health and mental health was mostly abandoned in favor of the idea that the mind and body were basically disconnected and should be treated separately.

But things have a way of coming full circle. Today, we see that a vast majority of mental health conditions involve neuroinflammation. Numerous studies have noted the connections between mental illness and leaky gut, a leaky blood-brain barrier, increased cytokines, and microglial activation.

Put another way, it seems that waste products and toxins may contribute to mental health challenges, if not in the way autointoxication proposed.

When mice are given lipopolysaccharides (LPSs), which are fragments of cell walls from dead bacteria, it leads directly to anxiety-related behaviors. Adult humans with major depressive disorder (MDD), schizophrenia, and bipolar disorder have all been shown to have increased cytokine levels as well as higher-than-normal amounts of mitochondrial content in their bloodstreams. That mitochondrial content has been released from the cells during a process of cellular cleansing known as apoptosis. Because of its bacterial DNA, that content is then recognized by the immune system as invasive bacteria. This triggers neuroinflammation and, by extension, higher potential for mental health struggles.

 

The Depressed Microbiome

Let’s take a look at the connections between depression and the gut — of which there are many.

Our gut bacteria can lead to depression via neuroinflammation stemming from dysbiosis and leaky gut. Dysbiosis can also lead to a change in neurotransmitter levels, which can lead to depression, and inflammation can also cause worsening dysbiosis and leaky gut.

Although the role of neurotransmitters in depression is widely known, many researchers leave the microbiome out of this discussion. But gut bacteria produce neurotransmitters either directly or they produce the precursors that your body needs to make neurotransmitters. Simply put, with an altered terrain, neurotransmitter levels become dysregulated. This is a major factor in depression.

Research shows that patients suffering from MDD have significantly altered microbiomes compared with healthy patients. Notably, patients with MDD have enriched proinflammatory bacteria and depleted anti-inflammatory, butyrate-producing bacteria. Patients with MDD also have a higher chance of suffering from leaky gut and higher levels of circulating cytokines.

Further, in 2022, a groundbreaking study looked at the microbiomes of more than a thousand patients with depression. They found alterations in 13 specific bacteria associated with depression. These specific bacteria are all known to be involved in the synthesis of glutamate, butyrate, serotonin, and GABA. And in patients with severe mental illness, increases in dysbiosis, levels of zonulin (with causes leaky gut), LPSs, and inflammation are all correlated with the severity of disease.

Inflammation doesn’t discriminate. Once your immune system gets the message that the fortress of your gut lining has been breached, that inflammation will become widespread and eventually get to your brain.

One study looked at the metabolites in the blood of three groups of people: those suffering from depression, those who were in remission from depression, and a control group. The people suffering from depression had significantly higher levels of glutamate and alanine and significantly lower levels of myo-inositol, GABA, phenylalanine, creatine, methionine, oleic acid, and tryptophan compared with the other two groups.

 

The Metabolite Problem

Balance is key when it comes to metabolites. Either too many or too few can cause problems. A balanced inner terrain should produce just the right amount of these substances; in patients suffering from depression, their microbiomes are not able to do their jobs correctly.

Low levels of tryptophan are especially notable in depression. Tryptophan is a precursor to serotonin and plays a role in its synthesis. It is also a precursor of 5-hydroxytryptamine, an amino acid needed to activate serotonin receptors — the main targets for conventional antidepressants.

What’s interesting is that antidepressants actually work their magic less on the serotonin receptors than on the microbiome. Research has found that SSRIs (selective serotonin reuptake inhibitors) change the makeup of the gut and even have direct antibacterial effects. One study compared the microbiomes of patients with MDD before and after they had been treated with an SSRI. Before treatment, their microbiomes showed reduced diversity and richness compared with controls. After treatment, their microbiomes had “normalized” and were comparable to those of healthy patients.

So, if SSRIs work by fixing the microbiome, then why not just go straight to the source and … fix the microbiome? That’s what I do in my practice. Meanwhile, have patience: The effects of SSRIs usually take a month to kick in, because it takes about that long to change your inner terrain.

 

Some Examples of Treating Depression Through the Gut

Treating depression by way of the gut can be done through several mechanisms:

 

Fecal Microbiota Transplant

A review of 21 human studies found that fecal microbiota transplants — repopulating the gut microbiome with diverse and healthy microbes — consistently led to a decrease in depression and anxiety symptoms among patients suffering from depression. A recent review also found that transplanting fecal microbiota from patients suffering from depression to healthy patients led to depression and anxiety symptoms in those previously healthy patients.

 

Probiotics and Prebiotics

Probiotics, which help rebalance the gut microbiome, can help regulate serotonin levels and reduce inflammation, leading to a reduction in symptoms of depression. And prebiotics (which feed our gut microbes) also seem to have antidepressant and antianxiety effects. A recent review looked at human studies from 2015 to 2023 on probiotics and prebiotics being used to treat depression. Researchers concluded that by attenuating inflammation and making serotonin more available, both prebiotics and probiotics significantly improved mood and reduced the severity of symptoms in patients suffering from depression.

 

Hydrogen Sulfide

Hydrogen sulfide (H₂S) is a signaling molecule made by your gut microbes, specifically when they ferment sulfur-containing compounds. H₂S plays an important role in nociception, which is your nervous system’s process of understanding noxious stimuli (heat, cold, mechanical force, or chemical stimulation).

When you experience pain, your gut microbes produce H₂S and send it to your brain to let you know you’re hurt. The H₂S then activates nociception neurons in the brain, which leads to the release of inflammatory cytokines and growth factors to heal the damage. When nociceptors are removed, the result is a defective tissue-protective reparative process. This happens because neurons do not get the signal that you’re in pain and need to heal.

Too little H₂S can lead to depression. When mice were treated with LPSs, it led to an increase in neuroinflammation and symptoms of depression. Both the inflammation and the symptoms were reversed with the administration of H₂S.

 

Vitamin D

Depression and vitamin D deficiency often occur together, so vitamin D supplements are another potential treatment for depression. It comes as no surprise that vitamin D has a positive impact on the gut. It increases gut diversity and the relative abundance of butyrate-producing bacteria, as well as some other particularly helpful gut microbes, like Akkermansia and Bifidobacterium. The result of these changes is less leaky gut and less inflammation. This may be why vitamin D also helps prevent dementia.

 

Psychedelics

Much like SSRIs, psychedelic drugs work with the gut to help alleviate depression. Ketamine, for example, can profoundly reduce inflammation by making changes to the microbiome. When depressed mice were injected with ketamine for seven days, they had a significant increase in friendly gut microbes and a reduction of pathogens.

Our gut microbes also play a big role in the bioavailability of these drugs and their effects, because they play a big role in metabolizing psychedelic substances. The uniqueness of our inner terrains may help explain why the effects of psychedelics tend to vary so much between individuals.

For instance, Bifidobacterium, which is linked to dopamine and addiction, modulates the metabolism of DMT, the psychoactive compound in ayahuasca. Another species of bacteria, Enterococcus faecalis, produces a critical enzyme to degrade LSD. There are specific bacterial strains that can metabolize mescaline, a psychoactive compound found in the peyote cactus. An insufficient microbial terrain will make it difficult to receive any benefit from these treatments.

That means patients with dysbiosis and leaky gut, which can cause inflammation and depression, are the least likely to be able to metabolize psychedelics. This is just one reason I think it’s critical to heal the microbiome before attempting to treat depression with any of these substances.

 

The Root of the Problem

The gut is the real root of neuroinflammation, which, in turn, is the real root of neurodegeneration and many common mental health and cognitive issues. With our disrupted inner terrains, many of us now have leaky gut, causing a near-constant activation of the immune system and chronic neuroinflammation. It’s a recipe for disaster, but it can be turned around, along with the diseases and symptoms that it causes.

Adapted from “THE GUT-BRAIN PARADOX” by Dr. Steven R. Gundry. Copyright © 2025 by Dr. Steven R. Gundry. Reprinted courtesy of Harper, an imprint of HarperCollins Publishers. Available wherever books are sold.

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