Schizophrenia (SCZ) is a disabling psychiatric disorder that places a heavy burden on patients, families, and health systems. Despite available antipsychotic medications, many patients experience persistent symptoms, making effective treatment and long-term recovery a continuing challenge.
Emerging research suggests a link between gut dysbiosis and SCZ. This IPA blog describes the plausible mechanisms and the growing field of studies exploring the potential of microbiome-based therapies.
Schizophrenia, in brief
More than 50 million people globally suffer from SCZ. Men and women are affected by SCZ in roughly equal numbers. However, men typically develop the illness three to five years earlier than women do and often experience more severe symptoms.
SCZ symptoms fall into three clinical categories of diverse psychopathologies: positive (hallucinations, delusions— hence not in the traditional use of the term “positive”), negative (apathy, social withdrawal), and cognitive (impaired thinking). Considered the gold standard in testing, the Positive and Negative Syndrome Scale (PANSS) assesses symptom severity and treatment response. Negative and cognitive symptoms drive most of the long-term disability, as they respond poorly to antipsychotic therapy.
Etiology
The pathophysiology of SCZ is increasingly understood as a convergence of genetic vulnerability, neurodevelopmental disruption, and environmental stressors. Together, these factors alter brain connectivity and immune signaling, shaping the disorder’s complex presentation.
SCZ was once thought to result mainly from dopamine dysregulation. Current models, however, point to a broader interplay among neurotransmitter imbalances—including dopamine, glutamate, and γ-aminobutyric acid (GABA)—as well as oxidative stress and neuroinflammation that disrupt neural circuits governing cognition and emotion.
Treatment
Current treatments rely primarily on dopamine D2 receptor antagonists (antipsychotics), which can reduce positive symptoms but not the underlying dysfunctions, leaving negative and cognitive symptoms largely unaddressed.
Gut microbiota and schizophrenia
SCZ may stem not only from abnormalities in the brain but also from gut-derived signals that influence neural function.
Emerging evidence links SCZ to immune dysfunction rooted in the gut, where microbial imbalances, inflammation, and barrier defects intersect with genetic and environmental risk factors. These disruptions appear to influence brain pathology through gut–brain immune pathways.
Indeed, research consistently shows that individuals with SCZ have distinct shifts in gut microbial composition compared with healthy controls. These changes include reductions in SCFA-producing bacteria and increases in proinflammatory, neurotransmission-disrupting species. Though causality remains unclear, these alterations are linked to greater inflammation, metabolic disruption, and symptom severity.
Furthermore, altered microbiota composition in SCZ is correlated to reduced gray matter volume and other changes in brain structure and function.
It is also well established that gut dysbiosis in SCZ can compromise intestinal barrier integrity—resulting in “leaky gut”—allowing microbial products to enter circulation, trigger systemic and brain inflammation.
Mechanisms
Growing evidence suggests that gut microbes influence SCZ through three interconnected pathways:
• SCFA pathway: Reduced production of short-chain fatty acids such as butyrate, which normally strengthen the blood–brain barrier and suppress neuroinflammation, may contribute to cognitive and emotional symptoms.
• Tryptophan–kynurenine pathway: Inflammatory activation diverts tryptophan away from serotonin synthesis toward kynurenine and its neurotoxic metabolites, which can disrupt glutamate signaling and cognition.
• Neurotransmitter signaling pathway: Gut microbes directly and indirectly influence brain chemicals such as dopamine, glutamate, and GABA; dysbiosis may disturb this balance and exacerbate psychotic and cognitive symptoms.
Microbiome-based therapies in schizophrenia
Microbial dysbiosis may be a modifiable risk factor, opening the door to microbiome-based therapies such as probiotics, prebiotics, diet and fecal microbiota transplantation (FMT)for SCZ.
Probiotics
Clinical trials using lactobacilli and bifidobacteria strains in SCZ suggest that probiotics may modestly reduce symptom severity and improve gut and immune markers.
- In a 14-week trial, supplementation with strains of Lacticaseibacillus rhamnosus and Bifidobacterium animalis led to reduced inflammatory markers and modulation of cytokine pathways linked to neuroimmune signaling.
- In one trial, Bifidobacterium breve supplementation for four weeks in individuals with SCZ led to improvements in anxiety, depression, and overall PANSS scores.
- In a six-week study, patients with SCZ treated with risperidone (an antipsychotic) plus probiotics showed greater improvements in clinical symptoms, lower levels of the inflammatory marker IL-6, and larger reductions in total PANSS scores compared to those receiving risperidone alone.
In addition, probiotics may act synergistically with nutrient supplements such as selenium and vitamin D, both of which are often deficient in SCZ and play key roles in antioxidant and immune function.
- For example, one study found that a 12-week multi-strain probiotic supplement and Vitamin D in SCZ patients improved total and PANSS scores as well as their metabolic profiles.
- With regard to selenium, one study found that its addition to probiotic supplementation for 12 weeks to SCZ patients had beneficial effects on the PANSS score and some metabolic profiles.
And recently, a 2025 meta-analysis of randomized clinical trials found that probiotic supplementation significantly reduced SCZ symptoms as measured by PANSS scores, though the limited number of studies means stronger evidence is still needed.
Prebiotics
Prebiotics support commensal gut bacteria, helping counteract dysbiosis and promote gut–brain signaling. Though clinical evidence in SCZ is limited, preclinical studies suggest prebiotics can reduce neuroinflammation, restore microbial balance, and support stress resilience and cognition. In mice, galactooligosaccharides—prebiotic fibers— reduced olanzapine-induced weight gain and neuroinflammation without affecting the drug’s action, suggesting prebiotics may help mitigate antipsychotic side effects.
Diet
Dietary interventions like the Mediterranean Diet*—an anti-inflammatory eating pattern—may help counteract immune and metabolic dysfunction in SCZ. They do so by promoting SCFA-producing gut bacteria such as Faecalibacterium and Roseburia, which are typically reduced in SCZ patients. Studies of dietary intake show that most individuals with SCZ consume low-fiber, high-fat, and highly processed foods, limiting the growth of these beneficial microbes.
* The Mediterranean Diet is composed of abundant fruits, vegetables, whole grains, beans, nuts, and seeds, with extra virgin olive oil and fatty fish as the primary fat sources and less red meat and sweets.
Fecal microbiota transplantation
FMT, which transfers gut microbes from a healthy donor to a recipient, is being studied as a potential therapy, with research showing that microbiota from individuals with SCZ can induce SCZ-like behaviors in healthy mice.
Overall, the current evidence suggests that, though not a replacement for antipsychotics, microbiome-focused therapies may improve outcomes and support expanding SCZ treatment beyond dopamine-targeted approaches.
Takeaway
SCZ is a devastating psychiatric disorder that profoundly disrupts thinking, emotion, and daily functioning, and while antipsychotics are the main treatment, many symptoms remain inadequately controlled, driving interest in complementary approaches. Emerging evidence links SCZ to gut dysbiosis, increased gut permeability, and immune dysfunction, which may influence brain function through the gut-brain axis. Microbiome alterations in SCZ include reductions in SCFA-producing bacteria and increases in proinflammatory species, which correlate with inflammation, metabolic disruption, and changes in brain structure and function. Microbiome-focused therapies—such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation—show promise in modulating neuroinflammation, neurotransmitter balance, and symptom severity. While not a substitute for antipsychotics, these approaches could improve patient outcomes and point toward broader treatment strategies beyond conventional therapies.
Image by AartlistDesign from Pixabay
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