Enhancing Colorectal Cancer Treatment: The Role of Bifidobacterium in Modulating Gut Immunity and Mitigating Capecitabine-Induced Toxicity

Aswathi Ramesh ¹, Dhasarathdev Srinivasan ¹, Rajasekaran Subbarayan ^1,2*, Ankush Chauhan ², Loganathan Krishnamoorthy ³, Jeevan Kumar ⁴, Madhan Krishnan ⁵, Rupendra Shrestha ⁶

1. Centre for Advanced Biotherapeutics and Regenerative Medicine, Faculty of Research, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India.
2. Centre for Herbal Pharmacology and Environmental Sustainability, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India.
3. Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India.
4. Department of Biomedical Sciences, The Apollo University, Chittoor, Andhra Pradesh, India.
5. Faculty of Research, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India.
6. Department of Natural and Applied Sciences, Nexus Institute of Research and Innovation (NIRI), Lalitpur, Nepal

Publications: Molecular Nutrition & Food Research (2025):e70023 doi: 10.1002/mnfr.70023

Abstract – Colorectal cancer (CRC) is the third leading cause of cancer-related mortality globally and presents significant challenges in treatment and patient care. Capecitabine, a widely used prodrug of 5-fluorouracil (5-FU), offers targeted delivery with reduced systemic toxicity compared to traditional chemotherapies. However, capacitabine is associated with adverse effects, such as hand-foot syndrome, gastrointestinal issues, and mucositis. Emerging evidence suggests that probiotics, particularly Bifidobacterium, play a pivotal role in gut microbiota modulation, promoting anti-inflammatory cytokines and short-chain fatty acids, such as butyrate, which possess both intestinal protective and anti-cancer properties. In this review, we explored the potential of Bifidobacterium to improve chemotherapy outcomes by mitigating inflammation and enhancing mucosal immunity in CRC patients. Furthermore, we demonstrated in silico approaches, including molecular docking and protein–protein interaction analysis, for Bifidobacterium and Toll-like receptor 2 (TLR-2), a key mediator of intestinal immunity. Docking results revealed strong binding affinity, suggesting the activation of anti-inflammatory pathways. Notably, this interaction enhanced IL-10 production while reducing pro-inflammatory cytokines, such as IL-6 and TNF-α, fostering gut homeostasis and mitigating chronic inflammation, a key driver of CRC progression. Therefore, future research should focus on personalized probiotics and validating their synergy with chemotherapy and immunotherapy to improve CRC treatment outcomes.

Cite: Ramesh A, Srinivasan D, Subbarayan R, Chauhan A, Krishnamoorthy L, Kumar J, Krishnan M, & Shrestha R. Enhancing Colorectal Cancer Treatment: The Role of Bifidobacterium in Modulating Gut Immunity and Mitigating Capecitabine-Induced Toxicity. Molecular Nutrition & Food Research. 2025:e70023.