Gut Microbiome Health May Predict Patient Response to Bipolar Disorder Treatment

Researchers have completed the first systematic review to explore the connection between bipolar medications and the gut microbiome, providing fresh insights into the complex relationship between the gut and brain.

The review, published in Microbiology, sheds light on how changes in the gut microbiome may affect the response to bipolar treatment, highlighting the potential for personalized therapies targeting the microbiome.

Bipolar disorder and treatment challenges

Bipolar disorder, a condition marked by extreme mood swings ranging from mania to depression, affects over 1% of the global population. Despite its prevalence, the disorder is often misdiagnosed or inadequately treated.

Many individuals with bipolar disorder do not respond well to medication, and previous studies have shown that their gut microbiomes differ from those of healthy individuals. This difference is thought to be linked to the gut-brain axis, a complex system where the gut and brain communicate via neurotransmitters and hormones.

Alterations in the gut microbiome can influence brain function, and conversely, changes in the brain caused by disorders like bipolar can affect the gut microbiome. This bidirectional relationship may complicate the treatment of bipolar disorder.

The impact of bipolar medications on the gut microbiome

Researchers from the University of Alberta conducted a systematic review to assess how medications used to treat bipolar disorder might alter the gut microbiome, and whether these changes could influence a patient's response to treatment.

The team reviewed data from 12 studies examining the effects of bipolar medications on both medicated and unmedicated patients. These studies compared the gut microbiome of patients before and after starting treatment, as well as between medicated individuals, those untreated, and healthy controls.

The findings indicate a significant connection between the gut microbiome and treatment outcomes in bipolar disorder. Patients who responded well to treatment – evidenced by alleviated depressive symptoms – showed gut microbiome profiles that resembled those of healthy individuals. In contrast, non-responders exhibited microbiome profiles that were distinct, suggesting that the microbiome could potentially serve as a biomarker for predicting treatment efficacy.

Moving towards personalized treatment strategies

Although the relationship between the gut microbiome and bipolar disorder is not yet fully understood, the review’s findings open the door for further research into personalized treatment options. The researchers suggest that by identifying specific microbiome profiles associated with positive treatment responses, clinicians could tailor therapy to better suit individual patients, potentially improving outcomes. The researchers also note that additional studies are needed to clarify the causal relationship between the gut microbiome and brain function in the context of bipolar disorder.

“We don’t know the direction in which this occurs, whether the drugs change the gut microbiome and this changes the way the brain functions, or whether the drugs change the way the brain functions which in turn, affects the gut microbiome," said lead study author An Bui, from the Department of Psychiatry at the University of Alberta

The team hopes that these findings may inspire future clinical trials that focus on microbiome-targeted therapies, offering a new approach to managing bipolar disorder.

"The review is important as it brings up more questions and suggestions for future research on how the gut microbiome affects bipolar treatment responses and vice versa," said Dr Andrew Greenshaw, study author and a professor of psychiatry and neuroscience at the University of Alberta. "Also, since the research subject is still new, synthesizing such diverse results with heterogeneous experimental methodologies can be helpful in guiding researchers design new studies."

Reference: Bui TA, O’Croinin BR, Dennett L, Winship IR, Greenshaw AJ. Pharmaco-psychiatry and gut microbiome: a systematic review of effects of psychotropic drugs for bipolar disorder. Microbiol. 2025;171(6). doi: 10.1099/mic.0.001568

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