The gut-brain axis is a key player in mental illnesses such as schizophrenia, bipolar disorder, depression, and anxiety.

The intestinal microbiome (the foundation of the gut-brain axis) influences brain function through bidirectional communication via neural (vagus nerve), immune (cytokines), and metabolic pathways. Microbiota alterations may also impair hypothalamic-pituitary-adrenal axis regulation, which, in turn, affects both psychological stress level (cortisol) and whole-body hormonal balance. What’s more, microbial metabolites (such as short-chain fatty acids (SCFAs)) and inflammation play roles in psychiatric symptoms.

When the intestinal microbiome gets out of whack, it’s called dysbiosis. Dysbiosis (imbalanced microbiota) has been linked to a plethora of psychiatric disorders. Dysbiosis may contribute to neuroinflammation, altered neurotransmitter production (which can affect brain signaling), and impaired brain connectivity. Dysbiosis can increase gut permeability (leaky gut), allowing inflammatory molecules to enter the bloodstream, disrupt blood-brain barrier integrity, and assault the brain.

Now that you’ve got the basics, let’s get down to the nitty gritty.

Schizophrenia

A 2024 report by Chinese scientists studying schizophrenia patients analyzed fecal samples using RNA gene sequencing. Schizophrenia patients exhibited significantly lower microbial diversity compared to controls, indicating a less diverse gut microbiome. It may be said that your noodle benefits from a good dose of colonic DEI. What’s more, schizophrenia patients had a lower abundance of beneficial bacteria like Faecalibacterium, Roseburia, Blautia, and Eubacterium (which produce anti-inflammatory short-chain fatty acids, SCFAs). Other studies have also noted a diminished population of Bifidobacterium in schizophrenics.

On the flip side of the coin, researchers noted that the mentally ill population harbored an overgrowth of potentially pathogenic bacteria like Prevotella, Succinivibrio, Fusobacterium, Megasphaera, and Clostridium. Other studies have also noted an increased microbial population of Proteobacteria and Lactobacillus in schizophrenics. All in all, these shifts suggest a dysbiotic gut environment in schizophrenia.

Mood disorders

Mood disorders are a category of mental illnesses characterized by significant and persistent disruptions in a person’s emotional state, impacting their mood, behavior, and overall well-being. These disorders can manifest as prolonged periods of sadness, irritability, or hopelessness (depression), or as periods of pathologically elevated mood, energy, and activity (mania or hypomania), or both.

In 2019, Chinese researchers evaluated individuals with bipolar disorder and depression. Compared to healthy controls, both patient groups had altered gut microbiota, including reduced microbial diversity. Specifically, certain bacteria (e.g., Bacteroides and Prevotella) were less abundant in those with mood disorders, while others (e.g., Clostridium and Streptococcus) were more abundant.

In 2021, Swiss researchers published a review article that explored the relationship between gut microbiota and the development and progression of MDD and BD, emphasizing the gut-brain axis as a key mechanism.

Their review showed reduced microbial diversity in MDD patients, with lower abundance of beneficial bacteria (Bifidobacterium, Lactobacillus) and increased pro-inflammatory species. Altered microbial metabolites, like reduced butyrate, may contribute to depressive symptoms via inflammation and impaired neuroplasticity.

Similar dysbiosis patterns are observed in BD, particularly during depressive episodes, with shifts in microbial composition (increased Clostridium). Manic episodes show distinct microbial profiles, suggesting state-specific alterations.

In 2022, researchers in the Netherlands reviewed the role of the gut microbiome in major psychiatric disorders. Their analysis showed dysbiosis in MDD, BD, and SCZ, with reduced microbial diversity and specific bacterial changes compared to healthy controls. For example, lower levels of anti-inflammatory bacteria like Faecalibacterium are common in these disorders.

OK, you may be saying, but how in the world do bugs in your gut screw up your brain?

Glad you asked.

First of all, good gut bugs produce a plethora of SCFAs. When these beneficial bacteria are banished, the SCFA goes away. The lack of bacterial-derived anti-inflammatory SCFAs like butyrate may result in increased inflammation, which may cross the blood-brain barrier and negatively impact proper cerebral function. Good bugs produce good stuff, bad bugs make toxic substances. To state the case more delicately and esoterically: Metabolic dysbiosis due to bacterial choline dysmetabolism ultimately causes a pernicious load of trimethylamine N-oxide (TMAO). In 2016, Russian scientists linked TMAO to schizophrenia symptoms, potentially via neuroinflammation.

Brain cells (neurons) communicate with each other via chemicals called neurotransmitters. Bugs in the gut influence the concentration and availability of neurotransmitters such as dopamine, serotonin, and GABA, which are implicated in psychiatric disorders. For example, certain gut bacteria can metabolize tryptophan, a precursor to serotonin, potentially disrupting brain signaling.

Dysbiosis increases gut permeability (“leaky gut”), allowing lipopolysaccharides (LPS) and other inflammatory molecules to enter the bloodstream, triggering systemic inflammation that may reach the brain and exacerbate psychotic symptoms.

Psychiatric disorders have been associated with immune system abnormalities, and the microbiome modulates immune responses via cytokines and T-cell activity, potentially influencing symptom severity.

Is there anything I can do about it?

There’s increasing evidence that bolstering the microbiome with probiotic supplementation, prebiotics, dietary changes (such as the Mediterranean diet), and fecal microbiota transplantation may all play a role in alleviating psychiatric disorders.

Probiotics can modulate gut microbiota composition and function, potentially influencing brain activity and behavior.

In 2018, doctors at Johns Hopkins conducted a clinical trial to investigate whether probiotics could prevent rehospitalization in patients with BD. The probiotic group had a significantly lower rehospitalization rate compared to the placebo group.

Probiotics are also likely to improve MDD. In 2020, a review by Irish scientists highlighted studies suggesting probiotics may reduce depressive symptoms and improve mood. However, the scientists concluded that probiotics don’t improve schizophrenia.

In 2017, Canadian scientists explored Bifidobacterium’s effects on depression, anxiety, and brain activity in IBS patients. The probiotic group showed reduced depression scores and brain activity changes in emotional regulation areas.

• Prebiotics like inulin may promote SCFA-producing bacteria, potentially stabilizing one’s mental state.
• Prebiotics like galactooligosaccharides (GOS) may enhance beneficial bacteria and reduce inflammation.
• Prebiotics like fructooligosaccharides (FOS) may support beneficial bacteria and reduce stress responses.

Diet also influences microbiota and psychiatric outcomes. Diets rich in fiber, omega-3s, and fermented foods (e.g., yogurt, kefir) have been associated with reduced anxiety and lower depression risk. Specialized plants (such as garlic, onions, bananas, whole grains, and various fruits and vegetables fibers) are not wholly digested by the body, but are fermented by gut bacteria and may act as food for beneficial bacteria, stimulating their growth and activity.

Last, but certainly not least, there’s a thing called a fecal medical transplant (FMT). During FMT a doctor harvests the poop of a healthy person and infuses it into the colon of someone who is ill. It’s not really the feces that they’re after. Lots of bacteria are hiding inside the poop and they are the gold for which the doctors are mining. It sounds outlandish, but FMT has saved the lives of thousands of people who would have otherwise died from toxic megacolon secondary to C. diff infection.

FMT in animal models has shown promise in reducing schizophrenia-like behaviors. In 2024, Chinese scientists conducted a transplant study using fecal microbiota from schizophrenia patients into mice, resulting in behavioral and gene expression changes resembling schizophrenia pathology.

Then, there’s the chicken and the egg quandary.

Mental illnesses can alter the microbiome (e.g., via stress or poor diet), and dysbiosis can worsen symptoms, creating a feedback loop. Psychiatric drugs like antipsychotics (e.g., risperidone) and antidepressants (e.g., SSRIs) can alter the microbiome, potentially influencing treatment outcomes.

So, as you can see, gut health and the health of our intestinal fellow travelers significantly impacts mental health. The good news is, there’s a bunch of stuff you can do to optimize the gut-brain axis.

Marc Arginteanu is a neurosurgeon and author of Azazel’s Public House.