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Cell-free Lacticaseibacillus rhamnosus-fermented cereal fraction attenuates 5-fluorouracil-induced intestinal mucositis in mice: Associations with redox homeostasis and epithelial structural preservation

Journal 2026 · IF 6.2 · 发表于 2026 年 8 月 23 日
作者: Wenhui Fu,Xuemeng Ji,Dongze Qin,Lingda Zhao,Huan Lv,Yaozhong Hu,Ruican Wang,Wentao Gu,Dongfei Tan,Shuo Wang
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摘要

Chemotherapy-induced intestinal mucositis is a common and clinically important adverse effect. However, its underlying mechanisms remain poorly understood and effective interventions are limited. This study investigated the protective effects of a cell-free L. rhamnosus -fermented cereal fraction against 5-fluorouracil (5-FU) induced CIIM in a murine model. L. rhamnosus fermentation markedly enhanced the functional value of the cereal matrix by enriching soluble fermentation-derived bioactives, including TCA-soluble peptide content, total phenolic and flavonoid content, and lactic acid. Prophylactic administration of the fermented cereal fraction attenuated 5-FU-induced mucosal injury, enhanced intestinal antioxidant capacity, improved mucosal architecture and barrier-related indices, and suppressed epithelial apoptosis. Exploratory quantitative proteomic analysis identified candidate proteins whose abundance was altered following 5-FU treatment, including proteins associated with antioxidant defense, apoptosis, cytoskeletal organization, and epithelial barrier-related processes. In contrast, fermented cereal intervention restored the expression of key endogenous antioxidant and barrier-associated proteins. Notably, the final pH-matched lactic acid control indicated that low final pH and the direct presence of lactic acid were insufficient to account for the protective effects of the fermented cereal fraction, suggesting that multiple fermentation derived components contributed to the observed bioactivity. Collectively, these findings indicate that L. rhamnosus -fermented cereal mitigates CIIM through fermentation-enhanced exogenous antioxidant delivery, support of endogenous antioxidant defenses, and attenuation of mucosal and barrier-related alterations. This study supports the potential of cereal fermentation-derived bioactives as functional dietary ingredients for managing CIIM.

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