Flavanones in Citrus unshiu peel (CUP) have been used as therapeutic agents to reduce intestinal inflammation; however, the anti-inflammatory effects of their biometabolites remain ambiguous. Here, we identified aglycone-type flavanones, such as hesperetin and naringenin, which were more abundant in the bioconversion of the CUP than in the ethanol extracts of the CUP. We found that the bioconversion of the CUP induced the canonical nuclear factor-κB pathway via degradation of IκB in Caco-2 cells. To check the immune suppressive capacity of the aglycones of the CUP in vivo, we orally administered the bioconversion of the CUP (500 mg/kg) to mice for two weeks prior to the 3% dextran sulfate sodium treatment. The CUP-pretreated group showed improved body weight loss, colon length shortage, and intestinal inflammation than the control mice. We also found a significant decrease in the population of lamina propria Th17 cells in the CUP-pretreated group following dextran sodium sulfate (DSS) treatment and an increase in mRNA levels of occludin in CUP-treated Caco-2 cells. Pyrosequencing analysis revealed a decreased abundance of Alistipes putredinis and an increased abundance of Muribaculum intestinale in the feces of the CUP-pretreated mice compared to those of the control mice. Overall, these findings suggest that the pre-administration of CUP biometabolites may inhibit the development of murine colitis by modulating intestinal permeability and the gut microbiome.

Background Advances in medical science improved cancer treatment outcomes, and radiotherapy became a common modality used by 50% of cancer patients. However, radiotherapy induces gastrointestinal distress, and it can severely impair patients’ quality of life. During irradiation, the gut microbiome is critical in maintaining intestinal health and influences the body’s response. This study examines the alterations in the gut microbiome and serum metabolites of prostate cancer patients undergoing radiotherapy. We investigate the potential radioprotective effects of Alistipes (A.) onderdonkii. Methods Ten patients with prostate cancer receiving radiotherapy were included in this study. Fecal and serum samples were collected, and diarrhea symptoms were monitored along with each radiotherapy section. Results After radiotherapy, nine microbiomes and 129 serum metabolites displayed significant changes associated with irradiation-induced gastrointestinal toxicity. Dehydroascorbic acid and A. onderdonkii found a correlation in the analysis between metabolites and the microbiome. Administration of A. onderdonkii significantly improved survival and reduced intestinal damage in mice after radiation exposure, suggesting A. onderdonkii as a protective agent in radiotherapy. Conclusions This result highlights A. onderdonkii as a potential microbial candidate for mitigating irradiation-induced damage in the gastrointestinal tract. It appears to alleviate oxidative stress and support mucosal integrity, thereby promoting resistance to radiation-induced injury. Impact This finding establishes the foundation for developing microbiome-based therapeutics for the gut health of cancer patients undergoing radiotherapy.