Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Effepharm (Shanghai) Co. Ltd, Shanghai, China.
Int J Radiat Biol. 2023;99(5):823-834. doi: 10.1080/09553002.2023.2145029. Epub 2022 Nov 16.
Radiation-induced intestinal fibrosis, a common complication of long-term survivors after receiving abdominal and pelvic radiotherapy, has no effective clinical drugs at present. Nicotinamide mononucleotide (NMN) has been reported to alleviate a variety of age-related diseases and has potential of regulating gut microbiota. The current study focuses on the role of gut microbiota in chronic radiation induced intestinal fibrosis, and investigates whether NMN plays a protective role in radiation-induced intestinal fibrosis as well as the impact of NMN on radiation-induced dysbiosis of gut microbiota.
C57BL/6J mice received 15 Gy abdominal irradiation and NMN (300 mg/kg/day) supplement in drinking water. Feces were collected at 4- and 8-months post-irradiation and performed 16S rRNA sequencing to detect the gut microbiota. Colon tissues were isolated at 12 months after irradiation with or without NMN supplementation for histological analysis.
We found that irradiation caused intestinal fibrosis, and altered the β diversity and composition of gut microbiota, while the gut microbiota was observed to be affected by time post-irradiation and age of mice. Long-term NMN supplementation alleviated intestinal fibrosis, and reshaped the composition and function of gut microbiota dysregulated by ionizing radiation (IR). In addition, , a promising probiotic, and metabolism-related pathways, such as Biosynthesis of other secondary metabolites and Amino acid metabolism, were more abundant after NMN treatment in irradiated mice.
IR has a long-term effect on the gut microbiota and NMN supplementation can alleviate radiation induced intestinal fibrosis by reshaping the composition of gut microbiota and regulating the metabolic function of the microorganism.
辐射诱导的肠道纤维化是接受腹部和盆腔放射治疗的长期幸存者的常见并发症，目前尚无有效的临床药物。烟酰胺单核苷酸（NMN）已被报道可缓解多种与年龄相关的疾病，并且具有调节肠道微生物群的潜力。本研究侧重于肠道微生物群在慢性辐射诱导的肠道纤维化中的作用，并研究 NMN 是否在辐射诱导的肠道纤维化中发挥保护作用以及 NMN 对辐射诱导的肠道微生物群失调的影响。
C57BL/6J 小鼠接受 15Gy 腹部照射，并在饮用水中补充 NMN（300mg/kg/天）。在照射后 4 个月和 8 个月收集粪便，并进行 16S rRNA 测序以检测肠道微生物群。在照射后 12 个月，有无 NMN 补充的情况下分离结肠组织进行组织学分析。
我们发现照射导致肠道纤维化，并改变了肠道微生物群的β多样性和组成，而肠道微生物群受到照射后时间和小鼠年龄的影响。长期 NMN 补充可减轻肠道纤维化，并重塑电离辐射（IR）失调的肠道微生物群的组成和功能。此外，益生菌丰度增加，如，和与代谢相关的途径，如其他次生代谢物的生物合成和氨基酸代谢，在接受 NMN 治疗的照射小鼠中更为丰富。
IR 对肠道微生物群有长期影响，NMN 补充可通过重塑肠道微生物群的组成和调节微生物的代谢功能来缓解辐射诱导的肠道纤维化。
