Fecal Microbiota Transplantation Repairs Radiation Enteritis Through Modulating the Gut Microbiota-Mediated Tryptophan Metabolism

Yeqiang Tu; Lumeng Luo; Qiong Zhou; Juan Ni; Qiu Tang

doi:10.1667/RADE-23-00189.1

Fecal Microbiota Transplantation Repairs Radiation Enteritis Through Modulating the Gut Microbiota-Mediated Tryptophan Metabolism

Radiat Res. 2024 Apr 1. doi: 10.1667/RADE-23-00189.1. Online ahead of print.

Authors

Yeqiang Tu^{1

2

3}, Lumeng Luo^{1

2

3}, Qiong Zhou⁴, Juan Ni⁴, Qiu Tang^{1

2

3}

Affiliations

¹ Department of Radiation Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, Zhejiang, China.
² Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China.
³ Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, 310006, Zhejiang, China.
⁴ Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.

PMID: 38555945
DOI: 10.1667/RADE-23-00189.1

Abstract

Radiation enteritis is a common complication of abdominal and pelvic radiotherapy. Several previous studies showed that fecal microbiota transplantation (FMT) could alleviate radiation enteritis. In this study, we investigated the efficacy of FMT in alleviating radiation enteritis and explored the mechanisms by multi-omics approaches. Briefly, C57BL/6J mice were subjected to 9 Gy irradiation to the localized abdominal field, and randomized received FMT from healthy donor mice or saline. H&E staining of harvested small intestine showed FMT decreased epithelial injury. Radiation-induced microbiota dysbiosis, characterized by a decrease in beneficial bacteria Lactobacillaceae and Lachnospiraceae, while these bacteria were restored by FMT. Fecal metabolomics analysis revealed that FMT modulated metabolic dysregulation. Two tryptophan pathway metabolites, indole-3-acetaldehyde and N-Acetyl-5-hydroxytryptamine were decreased after irradiation, whereas these metabolites showed a pronounced recovery in mice receiving FMT. Proteomics analysis of small intestine indicated that radiation enteritis triggered immune-inflammatory responses, which were potentially mitigated by FMT. In 21 patients receiving pelvic radiotherapy for cervical cancer, those who developed enteritis (n = 15) had higher abundance in Lachnospiraceae. Moreover, Indole-3-acetaldehyde was reduced after irradiation. These findings provide insights into the therapeutic effects of FMT in radiation enteritis and highlight Lachnospiraceae and the tryptophan metabolite, Indole-3-acetaldehyde may protect against radiation enteritis.