NMN alleviates radiation-induced intestinal fibrosis by modulating gut microbiota

Abstract

Aim

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.

Materials and methods

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.

Results

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.

Conclusion

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.

Keywords:

• Nicotinamide mononucleotide
• gut microbiota
• ionizing radiation
• intestinal fibrosis
• Akkermansia muciniphila

Institutional review board statement

This study was conducted according to the Guide for the Care and Use of Laboratory Animals published by the U.S. National Institutes of Health, and approved by the Institutional Committee for the Care and Use of Animals, Institute of Radiological Sciences, Chinese Academy of Medical Sciences (IRM-DWLL-2019154).

Author contributions

Xiaotong Zhao: Conceptualization, Methodology, Writing-Original draft preparation. Manman Zhang: Validation, Formal analysis. Kaihua Ji: Data curation. Hao Huang: Investigation, Resources. Feng Wang: Data curation. Yang Liu, Qiang Liu: Conceptualization, Writing-Reviewing and Editing, Supervision, Funding acquisition.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [82072331, 81772243, 32171239, 81730086, 31900891, and 32170762], CAMS Innovation Fund for Medical Science [2021-I2M-1-042], the Natural Science Foundation of Tianjin City [19JCJQJC63500].

Notes on contributors

Xiaotong Zhao

Xiaotong Zhao, PhD, is a Postdoc at the Department of Radiation Biology, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.

Kaihua Ji

Kaihua Ji, PhD, is a Research Assistant Professor in the Department of Radiation Biology, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.

Manman Zhang

Manman Zhang, PhD, is a Research Assistant Professor in the Department of Radiation Biology, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.

Hao Huang

Hao Huang, PhD, is from Effepharm (Shanghai) Co. Ltd., Shanghai, China.

Feng Wang

Feng Wang, PhD, is a Professor in the Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

Yang Liu

Yang Liu, PhD, is an Associate Professor in the Department of Radiation Biology, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.

Qiang Liu

Qiang Liu, PhD, is a Professor in the Department of Radiation Biology, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.