Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages
ABSTRACTThe gut microbiota has been shown to influence the efficacy and toxicity of chemotherapy, thereby affecting treatment outcomes. Understanding the mechanism by which microbiota affects chemotherapeutic toxicity would have a profound impact on cancer management. In this study, we report that f...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2024.2319511 |
| _version_ | 1797296106375217152 |
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| author | Zhen He Hongyu Xie Haoyang Xu Jinjie Wu Wanyi Zeng Qilang He Christian Jobin Sanqing Jin Ping Lan |
| author_facet | Zhen He Hongyu Xie Haoyang Xu Jinjie Wu Wanyi Zeng Qilang He Christian Jobin Sanqing Jin Ping Lan |
| author_sort | Zhen He |
| collection | DOAJ |
| description | ABSTRACTThe gut microbiota has been shown to influence the efficacy and toxicity of chemotherapy, thereby affecting treatment outcomes. Understanding the mechanism by which microbiota affects chemotherapeutic toxicity would have a profound impact on cancer management. In this study, we report that fecal microbiota transplantation from oxaliplatin-exposed mice promotes toxicity in recipient mice. Splenic RNA sequencing and macrophage depletion experiment showed that the microbiota-induced toxicity of oxaliplatin in mice was dependent on macrophages. Furthermore, oxaliplatin-mediated toxicity was exacerbated in Il10-/- mice, but not attenuated in Rag1-/- mice. Adoptive transfer of macrophage into Il10-/- mice confirmed the role of macrophage-derived IL-10 in the improvement of oxaliplatin-induced toxicity. Depletion of fecal Lactobacillus and Bifidobacterium was associated with the exacerbation of oxaliplatin-mediated toxicity, whereas supplementation with these probiotics alleviated chemotherapy-induced toxicity. Importantly, IL-10 administration and probiotics supplementation did not attenuate the antitumor efficacy of chemotherapy. Clinically, patients with colorectal cancer exposed to oxaliplatin exhibited downregulation of peripheral CD45+IL-10+ cells. Collectively, our findings indicate that microbiota-mediated IL-10 production influences tolerance to chemotherapy, and thus represents a potential clinical target. |
| first_indexed | 2024-03-07T21:58:34Z |
| format | Article |
| id | doaj.art-dcd39c2da6064157906d24af5c374e05 |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-03-07T21:58:34Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-dcd39c2da6064157906d24af5c374e052024-02-24T12:31:35ZengTaylor & Francis GroupGut Microbes1949-09761949-09842024-12-0116110.1080/19490976.2024.2319511Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophagesZhen He0Hongyu Xie1Haoyang Xu2Jinjie Wu3Wanyi Zeng4Qilang He5Christian Jobin6Sanqing Jin7Ping Lan8Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Anesthesia, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaSchool of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangzhou, ChinaSchool of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangzhou, ChinaDepartment of Medicine, Division of Gastroenterology, University of Florida, Florida, USADepartment of Anesthesia, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaABSTRACTThe gut microbiota has been shown to influence the efficacy and toxicity of chemotherapy, thereby affecting treatment outcomes. Understanding the mechanism by which microbiota affects chemotherapeutic toxicity would have a profound impact on cancer management. In this study, we report that fecal microbiota transplantation from oxaliplatin-exposed mice promotes toxicity in recipient mice. Splenic RNA sequencing and macrophage depletion experiment showed that the microbiota-induced toxicity of oxaliplatin in mice was dependent on macrophages. Furthermore, oxaliplatin-mediated toxicity was exacerbated in Il10-/- mice, but not attenuated in Rag1-/- mice. Adoptive transfer of macrophage into Il10-/- mice confirmed the role of macrophage-derived IL-10 in the improvement of oxaliplatin-induced toxicity. Depletion of fecal Lactobacillus and Bifidobacterium was associated with the exacerbation of oxaliplatin-mediated toxicity, whereas supplementation with these probiotics alleviated chemotherapy-induced toxicity. Importantly, IL-10 administration and probiotics supplementation did not attenuate the antitumor efficacy of chemotherapy. Clinically, patients with colorectal cancer exposed to oxaliplatin exhibited downregulation of peripheral CD45+IL-10+ cells. Collectively, our findings indicate that microbiota-mediated IL-10 production influences tolerance to chemotherapy, and thus represents a potential clinical target.https://www.tandfonline.com/doi/10.1080/19490976.2024.2319511Chemotherapy-induced toxicitymicrobiotainterleukin-10macrophage |
| spellingShingle | Zhen He Hongyu Xie Haoyang Xu Jinjie Wu Wanyi Zeng Qilang He Christian Jobin Sanqing Jin Ping Lan Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages Gut Microbes Chemotherapy-induced toxicity microbiota interleukin-10 macrophage |
| title | Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages |
| title_full | Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages |
| title_fullStr | Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages |
| title_full_unstemmed | Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages |
| title_short | Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages |
| title_sort | chemotherapy induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin 10 from macrophages |
| topic | Chemotherapy-induced toxicity microbiota interleukin-10 macrophage |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2024.2319511 |
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