Mind-Altering Microbes: The Gut Connection to Bipolar Disorder
Mira Jiang
Bipolar disorder is a mental health condition characterized by intense mood swings, alternating between periods of mania or hypomania and episodes of depression. Manic phases can involve euphoria, excessive energy, or irritability, while depressive episodes often bring fatigue, sadness, and hopelessness. The disorder’s development is linked to a complex interplay of genetic, neurochemical, and environmental factors. Because symptoms primarily manifest in mood and behavior, research has traditionally focused on the brain. However, recent studies suggest that interactions within the gut microbiome may also contribute to the disorder.
The gut-brain axis, a bidirectional communication system between the digestive tract and the brain, is heavily influenced by the trillions of microorganisms in the gut. Research has found notable differences between the microbiomes of healthy individuals and those with bipolar disorder, including reduced microbial diversity and elevated levels of specific bacteria like Flavonifractor that are associated with oxidative stress (Lu et al., 2019). These microbial imbalances vary across different disorder types and even between mood cycles, indicating a potential role in symptom manifestation.
While it may seem surprising that gut microorganisms can significantly impact mental health, the mechanisms involved—such as inflammation and altered hormone signaling—align with our current understanding of disease progression. Gut bacteria modulate intestinal permeability, and when the typical balance is unsettled, this permeability can increase and allow harmful substances to enter the bloodstream. Bacteria and toxins can escape the intestines and trigger systemic inflammation that can affect the central nervous system, potentially contributing to the mood disturbances seen in bipolar disorder.
The cytokines produced from neuroinflammation further lead to dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, which controls the body's stress response through cortisol production. Inflammation causes hyperactivation of this axis and excessive cortisol signaling which can induce depressive symptoms in bipolar disorder (Ahmad et al., 2021).
Given many aspects of the disease may arise from bacterial imbalances, finding ways to modulate the gut microbiome of bipolar patients could prove to be a promising avenue for novel therapies. Indeed, a study by Dickerson et al. found that probiotics reduced the risk of rehospitalization in patients experiencing acute mania. While this research is promising, further studies are needed to determine the most effective strains of probiotics and whether these benefits extend to other aspects of bipolar disorder.
The connection between gut health and bipolar disorder represents a developing frontier in mental health research. Existing evidence suggests that targeting the gut microbiome could provide a promising avenue for new treatments, potentially reducing symptom severity or stabilizing mood fluctuations. Future studies will likely focus on identifying specific bacterial strains involved in the disease and examining targeted interventions, such as dietary changes or tailored probiotics. As we deepen our understanding of the gut-brain axis, these insights could ultimately lead to novel, microbiome-based therapies that improve outcomes for those living with bipolar disorder and offer an exciting new dimension to understanding mental health.
About the Author
Mira Jiang (‘26) is a junior at Harvard College concentrating in neuroscience.
References
The gut-brain axis, a bidirectional communication system between the digestive tract and the brain, is heavily influenced by the trillions of microorganisms in the gut. Research has found notable differences between the microbiomes of healthy individuals and those with bipolar disorder, including reduced microbial diversity and elevated levels of specific bacteria like Flavonifractor that are associated with oxidative stress (Lu et al., 2019). These microbial imbalances vary across different disorder types and even between mood cycles, indicating a potential role in symptom manifestation.
While it may seem surprising that gut microorganisms can significantly impact mental health, the mechanisms involved—such as inflammation and altered hormone signaling—align with our current understanding of disease progression. Gut bacteria modulate intestinal permeability, and when the typical balance is unsettled, this permeability can increase and allow harmful substances to enter the bloodstream. Bacteria and toxins can escape the intestines and trigger systemic inflammation that can affect the central nervous system, potentially contributing to the mood disturbances seen in bipolar disorder.
The cytokines produced from neuroinflammation further lead to dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, which controls the body's stress response through cortisol production. Inflammation causes hyperactivation of this axis and excessive cortisol signaling which can induce depressive symptoms in bipolar disorder (Ahmad et al., 2021).
Given many aspects of the disease may arise from bacterial imbalances, finding ways to modulate the gut microbiome of bipolar patients could prove to be a promising avenue for novel therapies. Indeed, a study by Dickerson et al. found that probiotics reduced the risk of rehospitalization in patients experiencing acute mania. While this research is promising, further studies are needed to determine the most effective strains of probiotics and whether these benefits extend to other aspects of bipolar disorder.
The connection between gut health and bipolar disorder represents a developing frontier in mental health research. Existing evidence suggests that targeting the gut microbiome could provide a promising avenue for new treatments, potentially reducing symptom severity or stabilizing mood fluctuations. Future studies will likely focus on identifying specific bacterial strains involved in the disease and examining targeted interventions, such as dietary changes or tailored probiotics. As we deepen our understanding of the gut-brain axis, these insights could ultimately lead to novel, microbiome-based therapies that improve outcomes for those living with bipolar disorder and offer an exciting new dimension to understanding mental health.
About the Author
Mira Jiang (‘26) is a junior at Harvard College concentrating in neuroscience.
References
- Ahmad M. H., Rizvi M. A., Fatima M., Chandra Mondal A. (2021). Pathophysiological implications of neuroinflammation mediated HPA axis dysregulation in the prognosis of cancer and depression. Molecular and Cellular Endocrinology, 520, 111093. https://doi.org/10.1016/J.MCE.2020.111093.
- Dickerson F., Adamos M., Katsafanas E., Khushalani S., Origoni A., Savage C., et al. (2018). Adjunctive probiotic microorganisms to prevent rehospitalization in patients with acute mania: a randomized controlled trial. Bipolar Disorders, 20, 614–21. https://doi.org/10.1111/BDI.12652.
- Lu Q., Lai J., Lu H., Ng C., Huang T., Zhang H., et al. (2019). Gut microbiota in bipolar depression and its relationship to brain function: an advanced exploration. Front Psychiatry,10, 784. https://doi.org/10.3389/fpsyt.2019.00784.
- Ortega, M.A., Álvarez-Mon, M.A., García-Montero, C. et al. (2023). Microbiota–gut–brain axis mechanisms in the complex network of bipolar disorders: potential clinical implications and translational opportunities. Molecular Psychiatry, 28, 2645–2673. https://doi.org/10.1038/s41380-023-01964-w.
- Rowland, T. A., & Marwaha, S. (2018). Epidemiology and risk factors for bipolar disorder. Therapeutic Advances in Psychopharmacology, 8(9), 251–269. https://doi.org/10.1177/2045125318769235.