Chemotherapy-Induced Remodeling of the Gut Microbiota-Inflammation Axis: Implications for the Course of Bipolar...

There is growing evidence that bipolar disorder, BD and cancer share several biological features, including immune dysregulation, gut microbiota alterations, and chronic inflammation. Chemotherapy remains a mainstay of cancer treatment but can substantially alter the gut microbial ecosystem, impair intestinal barrier integrity, and contribute to systemic inflammation. However, little research has been done on whether these changes brought on by chemotherapy affect how BD develops clinically. This review summarizes the mechanisms through which chemotherapy may modify the gut microbiota-inflammation axis, along with how these changes may impact BD via the microbiota-gut-brain axis. We discuss how intestinal barrier failure, microbial metabolite production, microbial composition, and inflammatory signaling pathways-such as the LPS-TLR4/NF-κB axis and NLRP3 inflammasome activation-are affected by chemotherapeutic drugs. We also investigate the role of gut-derived inflammatory responses in neuroinflammation, dysregulation of the hypothalamic-pituitary-adrenal,HPA axis, impaired neuroplasticity, neurotransmitter imbalance, and cognitive dysfunction, all of which may contribute to mood instability, treatment resistance, and neuroprogression in BD. We also evaluate developing microbiome-targeted therapies, such as probiotics, fecal microbiota transplantation, and dietary modification, and explore the possible therapeutic consequences of chemotherapy-induced microbiota remodeling for patients with concomitant cancer and BD. Taken together, the available evidence supports the possibility that chemotherapy-induced modification of the gut microbiota-inflammation axis may contribute to the clinical course of BD. This integrated mechanistic paradigm offers a potential platform for future translational research and the creation of tailored treatment approaches for patients with comorbid cancer and BD, despite the lack of direct clinical proof. This narrative review summarizes the current evidence linking chemotherapy-induced gut dysbiosis and inflammatory responses to the clinical course of bipolar disorder and discusses their potential implications for integrated therapeutic strategies.