Haroun Yara Adel, Alzyoud Abdulrahman Abdulla, Alizadeh Mohammad Taha, Mohamed Nashwa Ahmed, Bendardaf Riyad, Soliman Sameh S M
College of Pharmacy, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates.
College of Law, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates.
Nutr Res. 2025 Sep;141:10-33. doi: 10.1016/j.nutres.2025.07.007. Epub 2025 Jul 25.
Breast cancer remains a leading global health challenge, with treatment resistance posing significant obstacles to effective therapy. Emerging research highlights the pivotal role of dietary polyunsaturated fatty acids (PUFAs) and gut microbiota in modulating breast cancer progression and therapeutic outcomes. This review explores the interplay and potential relevance of the PUFA-microbiota-ferroptosis axis in breast cancer progression and therapy. Omega-3 PUFAs, abundant in diets like the Mediterranean, exhibit anti-inflammatory properties, promote beneficial gut microbiota, and enhance ferroptosis, thereby reducing tumor proliferation and resistance. Conversely, omega-6 PUFAs, prevalent in Western diets, can exacerbate inflammation and tumor aggressiveness when imbalanced. Gut microbiota, through the production of short-chain fatty acids and PUFA-derived metabolites, further regulate ferroptosis sensitivity and systemic inflammation. We are evaluating the mechanisms by which omega-3 PUFAs and probiotics restore gut dysbiosis, modulate the tumor microenvironment, and synergize with treatments like chemotherapy and immune checkpoint inhibitors. Taken together and considering the generally favorable safety profile of omega-3 PUFAs, these findings suggest that the PUFA-microbiota-ferroptosis axis may represent a promising avenue for further investigation as a complementary strategy to address treatment resistance and improve outcomes. This warrants further translational research to optimize its clinical utility in personalized breast cancer management. Regulatory frameworks are also crucial to ensuring the safe and ethical implementation of PUFA-based interventions in global breast cancer care.
乳腺癌仍然是一项重大的全球健康挑战，治疗耐药性对有效治疗构成了重大障碍。新出现的研究突出了膳食多不饱和脂肪酸（PUFAs）和肠道微生物群在调节乳腺癌进展和治疗结果方面的关键作用。本综述探讨了PUFA-微生物群-铁死亡轴在乳腺癌进展和治疗中的相互作用及潜在相关性。欧米伽-3 PUFAs在地中海饮食等膳食中含量丰富，具有抗炎特性，可促进有益的肠道微生物群，并增强铁死亡，从而减少肿瘤增殖和耐药性。相反，西方饮食中普遍存在的欧米伽-6 PUFAs失衡时会加剧炎症和肿瘤侵袭性。肠道微生物群通过产生短链脂肪酸和PUFA衍生代谢物，进一步调节铁死亡敏感性和全身炎症。我们正在评估欧米伽-3 PUFAs和益生菌恢复肠道生态失调、调节肿瘤微环境以及与化疗和免疫检查点抑制剂等治疗协同作用的机制。综合考虑欧米伽-3 PUFAs总体良好的安全性，这些发现表明，PUFA-微生物群-铁死亡轴可能是一个有前景的进一步研究途径，作为解决治疗耐药性和改善治疗结果的补充策略。这需要进一步的转化研究，以优化其在个性化乳腺癌管理中的临床应用。监管框架对于确保基于PUFA的干预措施在全球乳腺癌护理中的安全和伦理实施也至关重要。
