Schizophrenia is widely recognized as a heterogeneous disorder, meaning that patients with the same diagnosis often show very different symptoms. Some experience more positive symptoms like hallucinations and delusions, others have cognitive impairments such as disorganized thinking, and some show blunted affect or depression.

Current drug development assumes all schizophrenia cases are similar, focusing on shared neurotransmitters. But what if schizophrenia consists of distinct subtypes with unique causes and symptom clusters, perhaps even involving gut bacteria?

A new 2025 study identified Brain Subtypes (BSs), Gut Subtypes (GSs), and combined Brain-Gut Subtypes (B-GSs) with potential biomarkers, which could one day aid in precise diagnosis.

The Study

Researchers screened 768 individuals for psychotic symptoms and cognitive functions like memory, verbal learning, and attention. Stool samples were analyzed for 176 genera of gut bacteria, and participants underwent MRI scans to examine brain structures.

Using an innovative data-fusion technique, the team linked gut microbiota profiles to brain imaging results, revealing seven distinct biological subtypes with differences in brain structure, gut health, and symptom patterns.

Brain Subtypes

Key differences were found in white matter volume and functional connectivity:

BS1: Increased white matter in the frontal and temporal lobes, weak connectivity in networks like the Default Mode Network, Somatomotor Network, and Visual Network.

BS2: Opposite white matter changes but similar connectivity issues.

Gut Subtypes

Three gut subtypes emerged:

GS1: High levels of Collinsella, linked to inflammation.

GS2: Low Gemmiger, high Prevotella, correlated with severe symptoms.

GS3: Elevated Streptococcus, known to impact neurotransmitters.

Brain-Gut Links

Strong overlaps were seen, such as B-GS1 and B-GS2 aligning with BS2, reinforcing the connection between gut microbiota and brain structure.

Implications

Tailored treatments could emerge:

BS1 may benefit from structural therapies like Transcranial Magnetic Stimulation (TMS).

BS2 may respond better to dopamine-targeting antipsychotics like Risperidone and Cognitive Behavioral Therapy (CBT).

The association between specific gut bacteria and symptom clusters suggests potential for microbiome-based therapies.While the study’s limitations include sample demographics and uncontrolled lifestyle factors, it marks a significant step towards understanding schizophrenia as a biological disorder with targeted biological treatments.