Dysbiosis and psychosis
Part 1 Schizophrenia
The gut-brain axis is a key player in mental illnesses such as schizophrenia, bipolar disorder, depression, and anxiety. The microbiome, the community of microorganisms in the gut, influences brain function, mood, and behavior through multiple pathways, including immune system modulation, neurotransmitter production, and the vagus nerve. Dysbiosis (an imbalance in the gut microbiome, where there's an increase in harmful bacteria and a decrease in beneficial ones) is correlated with mental illness. Today’s post dives deeper into Schizophrenia, focusing on microbiome connections, mechanisms, evidence, and potential interventions.
A 2024 report by Chinese scientists studied 64 schizophrenia patients and compared them to 53 healthy controls. The researchers analyzed fecal (poop) 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 Lactobacillus in schizophrenics. All in all, these shifts suggest a dysbiotic gut environment in schizophrenia.
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, (as noted above) 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 shit. 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 schizophrenia. 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.
Schizophrenia is associated with immune system abnormalities, and the microbiome modulates immune responses via cytokines and T-cell activity, potentially influencing symptom severity.
Well, is there anything I can do about it?
Many people have advocated bolstering the microbiome with probiotic supplementation, prebiotics (specialized plants (such as garlic, onions, bananas, whole grains, and various fruits and vegetables fibers) that are not wholly digested by the body, but are fermented by gut bacteria may act as food for beneficial bacteria, stimulating their growth and activity), or even dietary changes (e.g., Mediterranean diet). Unfortunately, in 2020, a group of Irish scientists carefully evaluated the medical literature and discovered that prescribing probiotics (such as Lactobacillus and Bifidobacterium) doesn’t improve schizophrenia.
Perhaps, though, there’s a bigger gun that may prove effective. Believe it or not, 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.
What does this have to do with schizophrenia?
FMT in animal models has shown promise in reducing schizophrenia-like behaviors. In 2024, Chinese scientists transplanted fecal microbiota from patients with schizophrenia into mice. The researchers found that mice receiving these transplants exhibited schizophrenia-like behaviors compared to mice receiving microbiota from healthy humans. The affected mice showed altered expression of genes related to neuroinflammation, synaptic function, and neurotransmitter signaling (e.g., dopamine and glutamate pathways), which are implicated in schizophrenia pathology.
Want to learn about FMT for Alzheimer’s Disease? Check out https://brain2mind.substack.com/p/poop-transplant-and-alzheimers-disease