Gut‐derived Lactobacillus from exceptional responders mitigates chemoradiotherapy‐induced intestinal injury through methionine‐driven epigenetic modulation
Abstract Acute chemoradiotherapy‐induced intestinal injury (ACRIII) is a common and debilitating complication in patients with colorectal cancer, significantly impairing both quality of life and treatment outcomes. This study aimed to investigate the role of the gut microbiome in mitigating ACRIII....
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Wiley
2025-06-01
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| Online Access: | https://doi.org/10.1002/imt2.70043 |
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| author | Lu Yu Zhenhui Chen Shengqi Yin Qiqing Guo Yuchuan Chen Jiaying Li Yafang Wang Xiangqiang Liu Zi Xu Yaowei Zhang Yuqin Zhang Zhihao Zheng Keli Chen Yanqing Ding Hongying Fan Zhifeng Liu Yi Ding |
| author_facet | Lu Yu Zhenhui Chen Shengqi Yin Qiqing Guo Yuchuan Chen Jiaying Li Yafang Wang Xiangqiang Liu Zi Xu Yaowei Zhang Yuqin Zhang Zhihao Zheng Keli Chen Yanqing Ding Hongying Fan Zhifeng Liu Yi Ding |
| author_sort | Lu Yu |
| collection | DOAJ |
| description | Abstract Acute chemoradiotherapy‐induced intestinal injury (ACRIII) is a common and debilitating complication in patients with colorectal cancer, significantly impairing both quality of life and treatment outcomes. This study aimed to investigate the role of the gut microbiome in mitigating ACRIII. Through bioinformatics analysis of clinical fecal samples and fecal microbiota transplantation (FMT) experiments in mice, we identified a strong association between a high abundance of Lactobacillus species and the absence of ACRIII. From the fecal samples of rectal cancer patients who achieved complete remission without experiencing ACRIII during chemoradiotherapy, 10 novel Lactobacillus strains were isolated and characterized. Among these, Lacticaseibacillus rhamnosus DY801 exhibited a robust capacity to synthesize methionine through metB. This microbial methionine production modulated methionine metabolism in host gut lymphoid tissue inducer (Lti) cells, without diminishing the therapeutic efficacy of chemoradiotherapy. Supplementation with methionine increased intracellular levels of S‐adenosylmethionine and enhanced histone H3 lysine 4 trimethylation (H3K4me3) in Lti cells. These epigenetic modifications led to the suppression of pro‐inflammatory cytokines interleukin‐17A (IL‐17A) and interleukin‐22 (IL‐22), ultimately reducing ACRIII severity. Our findings suggest that specific Lactobacillus strains derived from patients with exceptional treatment responses may offer a novel therapeutic avenue for preventing or alleviating ACRIII. This microbiome‐based approach holds significant potential for improving patient outcomes and enhancing the tolerability of chemoradiotherapy in colorectal cancer. |
| format | Article |
| id | doaj-art-a7e7a675a29a41eeb142f64ab5661ff6 |
| institution | OA Journals |
| issn | 2770-596X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | iMeta |
| spelling | doaj-art-a7e7a675a29a41eeb142f64ab5661ff62025-08-20T02:24:23ZengWileyiMeta2770-596X2025-06-0143n/an/a10.1002/imt2.70043Gut‐derived Lactobacillus from exceptional responders mitigates chemoradiotherapy‐induced intestinal injury through methionine‐driven epigenetic modulationLu Yu0Zhenhui Chen1Shengqi Yin2Qiqing Guo3Yuchuan Chen4Jiaying Li5Yafang Wang6Xiangqiang Liu7Zi Xu8Yaowei Zhang9Yuqin Zhang10Zhihao Zheng11Keli Chen12Yanqing Ding13Hongying Fan14Zhifeng Liu15Yi Ding16Department of Radiation Oncology, Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou ChinaDepartment of Radiation Oncology, Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of Radiation Oncology, Nanfang Hospital Southern Medical University Guangzhou ChinaState Key Laboratory of Organ Failure Research, Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Department of Infectious Diseases, Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of Radiation Oncology, Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of Radiation Oncology, Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of Gastroenterology General Hospital of Southern Theatre Command Guangzhou ChinaDepartment of Radiation Oncology, Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of Radiation Oncology, Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of Radiation Oncology, Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of Radiation Oncology, Nanfang Hospital Southern Medical University Guangzhou ChinaHuiQiao Medical Center, Nanfang Hospital Southern Medical University Guangzhou ChinaGuangdong Province Key Laboratory of Molecular Tumor Pathology Guangzhou ChinaDepartment of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou ChinaThe Department of Critical Care Medicine General Hospital of Southern Theater Command of PLA Guangzhou ChinaDepartment of Radiation Oncology, Nanfang Hospital Southern Medical University Guangzhou ChinaAbstract Acute chemoradiotherapy‐induced intestinal injury (ACRIII) is a common and debilitating complication in patients with colorectal cancer, significantly impairing both quality of life and treatment outcomes. This study aimed to investigate the role of the gut microbiome in mitigating ACRIII. Through bioinformatics analysis of clinical fecal samples and fecal microbiota transplantation (FMT) experiments in mice, we identified a strong association between a high abundance of Lactobacillus species and the absence of ACRIII. From the fecal samples of rectal cancer patients who achieved complete remission without experiencing ACRIII during chemoradiotherapy, 10 novel Lactobacillus strains were isolated and characterized. Among these, Lacticaseibacillus rhamnosus DY801 exhibited a robust capacity to synthesize methionine through metB. This microbial methionine production modulated methionine metabolism in host gut lymphoid tissue inducer (Lti) cells, without diminishing the therapeutic efficacy of chemoradiotherapy. Supplementation with methionine increased intracellular levels of S‐adenosylmethionine and enhanced histone H3 lysine 4 trimethylation (H3K4me3) in Lti cells. These epigenetic modifications led to the suppression of pro‐inflammatory cytokines interleukin‐17A (IL‐17A) and interleukin‐22 (IL‐22), ultimately reducing ACRIII severity. Our findings suggest that specific Lactobacillus strains derived from patients with exceptional treatment responses may offer a novel therapeutic avenue for preventing or alleviating ACRIII. This microbiome‐based approach holds significant potential for improving patient outcomes and enhancing the tolerability of chemoradiotherapy in colorectal cancer.https://doi.org/10.1002/imt2.70043acute chemoradiotherapy‐induced intestinal injuryLactobacillusLacticaseibacillus rhamnosus DY801Lti cellsmethionine metabolismmetB |
| spellingShingle | Lu Yu Zhenhui Chen Shengqi Yin Qiqing Guo Yuchuan Chen Jiaying Li Yafang Wang Xiangqiang Liu Zi Xu Yaowei Zhang Yuqin Zhang Zhihao Zheng Keli Chen Yanqing Ding Hongying Fan Zhifeng Liu Yi Ding Gut‐derived Lactobacillus from exceptional responders mitigates chemoradiotherapy‐induced intestinal injury through methionine‐driven epigenetic modulation iMeta acute chemoradiotherapy‐induced intestinal injury Lactobacillus Lacticaseibacillus rhamnosus DY801 Lti cells methionine metabolism metB |
| title | Gut‐derived Lactobacillus from exceptional responders mitigates chemoradiotherapy‐induced intestinal injury through methionine‐driven epigenetic modulation |
| title_full | Gut‐derived Lactobacillus from exceptional responders mitigates chemoradiotherapy‐induced intestinal injury through methionine‐driven epigenetic modulation |
| title_fullStr | Gut‐derived Lactobacillus from exceptional responders mitigates chemoradiotherapy‐induced intestinal injury through methionine‐driven epigenetic modulation |
| title_full_unstemmed | Gut‐derived Lactobacillus from exceptional responders mitigates chemoradiotherapy‐induced intestinal injury through methionine‐driven epigenetic modulation |
| title_short | Gut‐derived Lactobacillus from exceptional responders mitigates chemoradiotherapy‐induced intestinal injury through methionine‐driven epigenetic modulation |
| title_sort | gut derived lactobacillus from exceptional responders mitigates chemoradiotherapy induced intestinal injury through methionine driven epigenetic modulation |
| topic | acute chemoradiotherapy‐induced intestinal injury Lactobacillus Lacticaseibacillus rhamnosus DY801 Lti cells methionine metabolism metB |
| url | https://doi.org/10.1002/imt2.70043 |
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