Gut Health and Bipolar Disorder: The Microbiome-Brain Connection
The gut microbiome is altered in bipolar disorder, with consistent reductions in beneficial bacteria like Faecalibacterium, and these changes correlate with illness severity—though current evidence does not yet support microbiome-targeted interventions as standard treatment outside of research settings. 1, 2
The Gut-Brain Axis in Bipolar Disorder
The relationship between gut health and bipolar disorder operates through the gut-brain axis—a bidirectional communication system connecting the gut and brain via the autonomic nervous system, HPA axis, and microbiome. 3 This is not simply one condition causing the other; rather, shared genetic risk factors exist between mood disorders and gut dysfunction, indicating common pathophysiological mechanisms. 3
Key Pathophysiological Mechanisms
- HPA axis dysregulation occurs in both bipolar disorder and gut disorders, making individuals more susceptible to stress and less able to recover from stressful events. 3, 4
- Microbiome alterations are consistently documented, with bipolar patients showing different gut bacterial compositions compared to healthy controls. 3, 1
- Inflammatory pathways link gut dysbiosis to mood symptoms through immune activation and gut barrier dysfunction. 5, 6
Specific Microbiome Changes in Bipolar Disorder
Research has identified distinct patterns of gut bacterial alterations in bipolar disorder:
- Decreased Faecalibacterium is the most robust finding, with this reduction correlating with worse health outcomes across multiple domains including depression severity (PHQ9), anxiety (GAD7), sleep quality (PSQI), and mania symptoms (ASRM). 1
- Increased Actinobacteria and decreased Firmicutes at the phylum level are observed across mental disorders including bipolar disorder. 2
- Lower microbiota diversity distinguishes bipolar patients from healthy controls. 7
- Greater abundance of Clostridiaceae and Collinsella (particularly in bipolar II) have been documented. 7
The fractional representation of Faecalibacterium specifically associates with better self-reported health outcomes independent of age, sex, and BMI—suggesting this may be a key therapeutic target. 1
Clinical Implications and Current Treatment Approach
What This Means for Practice
While the gut-brain connection in bipolar disorder is scientifically established, current clinical guidelines do not support microbiome-targeted interventions as standard treatment. 8 The evidence remains preliminary, with significant methodological limitations including:
- Small sample sizes and heterogeneous study designs 2, 6
- Insufficient control for confounding factors (medications, diet, smoking, BMI) 2, 7
- Variable methods for sample storage, analysis, and statistical reporting 2
Potential Adjunctive Approaches (Research Context Only)
- Probiotic supplementation has shown beneficial effects in mood disorders and IBS, with one small trial demonstrating improvement in both mood and gastrointestinal symptoms. 3
- Dietary interventions such as the Mediterranean diet may influence the microbiome and HPA axis, though this has been studied primarily in IBS with comorbid depression rather than bipolar disorder specifically. 3
- Fecal microbiota transplantation (FMT) is only recommended for recurrent C. difficile infection, not for bipolar disorder or depression, and should only be considered within research protocols. 8
Important Caveats and Clinical Pitfalls
Do not delay or substitute evidence-based bipolar disorder treatments (mood stabilizers, antipsychotics, psychotherapy) with microbiome-targeted interventions. 8 First-line treatments for bipolar disorder should continue to be pharmacotherapy and psychotherapy as recommended by established guidelines. 8
Screen for gastrointestinal comorbidities in bipolar patients, as the bidirectional relationship means gut symptoms can worsen psychiatric outcomes and vice versa. 3 Approximately 39% and 29% of patients with gut-brain axis disorders have comorbid anxiety and depression respectively. 3
Consider the impact of psychiatric medications on gut function—many psychotropic medications have gastrointestinal effects that may further alter the microbiome. 3
Future Directions
The data support the hypothesis that targeting the microbiome may eventually become an effective treatment paradigm for bipolar disorder. 1, 6 However, larger controlled trials are needed to:
- Identify optimal probiotic strains and dosing 5, 6
- Determine which bipolar patients are most likely to benefit from microbiome interventions 6
- Establish standardized protocols for microbiome assessment and manipulation 2, 6
- Assess long-term safety and efficacy of microbiome-targeted therapies 8
Until such evidence emerges, microbiome interventions for bipolar disorder should remain within research settings only. 8