연구성과 홍보

J Am Acad Dermatol. 2024 Sep;91(3):562-564.

Title : Estrogen-related receptor alpha mitigates radiation-induced bowel injury through gut enrichment of Bacteroides vulgatus

Authors : Seul Gi Shin1,2,3, June-Young Lee4, Jee-Won Choi4, Ji-Ho Yoo5, In-Chul Jeong4, Do-Yeon Kim4, Hyun Sik Kim4, Seungwha Paik1,2,3, Gyu-Yong Song6, Kyung-Hee Kim7, Jin-Man Kim7, Jin-Woo Bae4,5*, Eun-Kyeong Jo1,2*, Sup Kim8*

Affiliations :

1Department of Microbiology, Chungnam National University College of Medicine, Daejeon, South Korea.

2Department of Medical Science, Chungnam National University College of Medicine, Daejeon, South Korea.

3System Network Inflammation Control Research Center, Chungnam National University College of Medicine, Daejeon, South Korea.

4Department of Biology, Kyung Hee University, Seoul, South Korea.

5Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, South Korea.

6College of Pharmacy, Chungnam National University, Daejeon, South Korea.

7Department of Pathology, Chungnam National University School of Medicine, Daejeon, South Korea.

8Department of Radiation Oncology, Chungnam National University School of Medicine, Daejeon, South Korea.

DOI: 10.1016/j.jaad.2024.05.021

Abstract :

Radiation-induced gastrointestinal (GI) toxicity can be a major cause of morbidity in patients undergoing abdominal radiotherapy. There is an unmet need for treatments to ameliorate GI toxicity. Estrogen-related receptor alpha (ESRRA), a protein involved in the regulation of inflammation and autophagy, is widely expressed across human tissues. Our recent findings on ESRRA's significant contribution to intestinal homeostasis and inflammation control in inflammatory bowel disease inspired us to investigate its potential role in radiation-induced gastrointestinal injury. esrra-/- mice showed distinct gut microbiota composition and increased susceptibility to abdominal irradiation with significant alteration of microbiota and increased intestinal inflammation. B. vulgatus reversed gut pathology in esrra-/- mice by improving intestinal barrier function, reducing inflammation, and restoring the expression of Tfeb and its downstream genes. Additionally, in patients treated with abdominal radiotherapy, decreased ESRRA expression in rectal tissues correlated with increased IL-6 expression and radiation induced diarrhea. Our findings indicate that ESRRA contributes to intestinal homeostasis through gut enrichment of B. vulgatus.