NMN alleviates radiation-induced intestinal fibrosis by modulating gut microbiota

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, Akkermansia muciniphila, 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.