Department of Radiotherapy and Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China; Institute of Radiotherapy and Oncology, Soochow University, Suzhou, China.
Department of Radiotherapy and Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China; State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China.
Int J Radiat Oncol Biol Phys. 2024 Sep 1;120(1):189-204. doi: 10.1016/j.ijrobp.2024.03.003. Epub 2024 Mar 12.
Radiation-induced intestinal injury (RIII) commonly occur during abdominal-pelvic cancer radiation therapy; however, no effective prophylactic or therapeutic agents are available to manage RIII currently. This study aimed to clarify the potential of probiotic consortium supplementation in alleviating RIII.
Male C57BL/6J mice were orally administered a probiotic mixture comprising Bifidobacterium longum BL21, Lactobacillus paracasei LC86, and Lactobacillus plantarum Lp90 for 30 days before exposure to 13 Gy of whole abdominal irradiation. The survival rates, clinical scores, and histologic changes in the intestines of mice were assessed. The impacts of probiotic consortium treatment on intestinal stem cell proliferation, differentiation, and epithelial barrier function; oxidative stress; and inflammatory cytokines were evaluated. A comprehensive examination of the gut microbiota composition was conducted through 16S rRNA sequencing, while changes in metabolites were identified using liquid chromatography-mass spectrometry.
The probiotic consortium alleviated RIII, as reflected by increased survival rates, improved clinical scores, and mitigated mucosal injury. The probiotic consortium treatment exhibited enhanced therapeutic effects at the histologic level compared with individual probiotic strains, although there was no corresponding improvement in survival rates and colon length. Moreover, the probiotic consortium stimulated intestinal stem cell proliferation and differentiation, enhanced the integrity of the intestinal epithelial barrier, and regulated redox imbalance and inflammatory responses in irradiated mice. Notably, the treatment induced a restructuring of the gut microbiota composition, particularly enriching short-chain fatty acid-producing bacteria. Metabolomic analysis revealed distinctive metabolic changes associated with the probiotic consortium, including elevated levels of anti-inflammatory and antiradiation metabolites.
The probiotic consortium attenuated RIII by modulating the gut microbiota and metabolites, improving inflammatory symptoms, and regulating oxidative stress. These findings provide new insights into the maintenance of intestinal health with probiotic consortium supplementation and will facilitate the development of probiotic-based therapeutic strategies for RIII in clinical practice.
腹部-骨盆癌症放射治疗过程中常发生放射性肠损伤（RIII）；然而，目前尚无有效的预防或治疗药物来治疗 RIII。本研究旨在阐明益生菌联合体补充剂在缓解 RIII 方面的潜力。
雄性 C57BL/6J 小鼠在接受 13Gy 全腹部照射前 30 天经口给予包含长双歧杆菌 BL21、副干酪乳杆菌 LC86 和植物乳杆菌 Lp90 的益生菌混合物。评估小鼠的存活率、临床评分和肠道组织学变化。评估益生菌联合体治疗对肠道干细胞增殖、分化和上皮屏障功能、氧化应激和炎症细胞因子的影响。通过 16S rRNA 测序对肠道微生物群落组成进行全面检查，通过液相色谱-质谱联用鉴定代谢物变化。
益生菌联合体通过提高存活率、改善临床评分和减轻黏膜损伤来缓解 RIII。与单一益生菌株相比，益生菌联合体治疗在组织学水平上表现出增强的治疗效果，尽管存活率和结肠长度没有相应改善。此外，益生菌联合体刺激肠道干细胞增殖和分化，增强了肠道上皮屏障的完整性，并调节了照射小鼠的氧化还原失衡和炎症反应。值得注意的是，该治疗方法引起了肠道微生物群落组成的重构，特别是富含产生短链脂肪酸的细菌。代谢组学分析显示，与益生菌联合体相关的代谢物发生了独特的变化，包括抗炎和抗辐射代谢物水平升高。
益生菌联合体通过调节肠道微生物群和代谢物来减轻 RIII，改善炎症症状并调节氧化应激。这些发现为益生菌联合体补充维持肠道健康提供了新的见解，并将促进基于益生菌的 RIII 治疗策略在临床实践中的发展。
