Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolites
Abstract Diet has emerged as a key impact factor for gut microbiota function. However, the complexity of dietary components makes it difficult to predict specific outcomes. Here we investigate the impact of plant-derived nanoparticles (PNP) on gut microbiota and metabolites in context of cancer immu...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56498-2 |
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| author | Yun Teng Chao Luo Xiaolan Qiu Jingyao Mu Mukesh K. Sriwastva Qingbo Xu Minmin Liu Xin Hu Fangyi Xu Lifeng Zhang Juw Won Park Jae Yeon Hwang Maiying Kong Zhanxu Liu Xiang Zhang Raobo Xu Jun Yan Michael L. Merchant Craig J. McClain Huang-Ge Zhang |
| author_facet | Yun Teng Chao Luo Xiaolan Qiu Jingyao Mu Mukesh K. Sriwastva Qingbo Xu Minmin Liu Xin Hu Fangyi Xu Lifeng Zhang Juw Won Park Jae Yeon Hwang Maiying Kong Zhanxu Liu Xiang Zhang Raobo Xu Jun Yan Michael L. Merchant Craig J. McClain Huang-Ge Zhang |
| author_sort | Yun Teng |
| collection | DOAJ |
| description | Abstract Diet has emerged as a key impact factor for gut microbiota function. However, the complexity of dietary components makes it difficult to predict specific outcomes. Here we investigate the impact of plant-derived nanoparticles (PNP) on gut microbiota and metabolites in context of cancer immunotherapy with the humanized gnotobiotic mouse model. Specifically, we show that ginger-derived exosome-like nanoparticle (GELN) preferentially taken up by Lachnospiraceae and Lactobacillaceae mediated by digalactosyldiacylglycerol (DGDG) and glycine, respectively. We further demonstrate that GELN aly-miR159a-3p enhances anti-PD-L1 therapy in melanoma by inhibiting the expression of recipient bacterial phospholipase C (PLC) and increases the accumulation of docosahexaenoic acid (DHA). An increased level of circulating DHA inhibits PD-L1 expression in tumor cells by binding the PD-L1 promoter and subsequently prevents c-myc-initiated transcription of PD-L1. Colonization of germ-free male mice with gut bacteria from anti-PD-L1 non-responding patients supplemented with DHA enhances the efficacy of anti-PD-L1 therapy compared to controls. Our findings reveal a previously unknown mechanistic impact of PNP on human tumor immunotherapy by modulating gut bacterial metabolic pathways. |
| format | Article |
| id | doaj-art-cd8e13f111294a24a6cbf7b6645e7507 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-cd8e13f111294a24a6cbf7b6645e75072025-02-09T12:44:50ZengNature PortfolioNature Communications2041-17232025-02-0116112510.1038/s41467-025-56498-2Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolitesYun Teng0Chao Luo1Xiaolan Qiu2Jingyao Mu3Mukesh K. Sriwastva4Qingbo Xu5Minmin Liu6Xin Hu7Fangyi Xu8Lifeng Zhang9Juw Won Park10Jae Yeon Hwang11Maiying Kong12Zhanxu Liu13Xiang Zhang14Raobo Xu15Jun Yan16Michael L. Merchant17Craig J. McClain18Huang-Ge Zhang19Brown Cancer Center, University of Louisville School of MedicineBrown Cancer Center, University of Louisville School of MedicineBrown Cancer Center, University of Louisville School of MedicineBrown Cancer Center, University of Louisville School of MedicineBrown Cancer Center, University of Louisville School of MedicineDepartment of Microbiology and Immunology, University of LouisvilleBrown Cancer Center, University of Louisville School of MedicineDepartment of Genomic Medicine, University of Texas MD Anderson Cancer CenterBrown Cancer Center, University of Louisville School of MedicineBrown Cancer Center, University of Louisville School of MedicineBrown Cancer Center, University of Louisville School of MedicineBrown Cancer Center, University of Louisville School of MedicineBrown Cancer Center, University of Louisville School of MedicineBrown Cancer Center, University of Louisville School of MedicineDepartment of Pharmacology and Toxicology, University of LouisvilleDepartment of Pharmacology and Toxicology, University of LouisvilleBrown Cancer Center, University of Louisville School of MedicineKidney Disease Program and Clinical Proteomics Center, University of LouisvilleDepartment of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of MedicineBrown Cancer Center, University of Louisville School of MedicineAbstract Diet has emerged as a key impact factor for gut microbiota function. However, the complexity of dietary components makes it difficult to predict specific outcomes. Here we investigate the impact of plant-derived nanoparticles (PNP) on gut microbiota and metabolites in context of cancer immunotherapy with the humanized gnotobiotic mouse model. Specifically, we show that ginger-derived exosome-like nanoparticle (GELN) preferentially taken up by Lachnospiraceae and Lactobacillaceae mediated by digalactosyldiacylglycerol (DGDG) and glycine, respectively. We further demonstrate that GELN aly-miR159a-3p enhances anti-PD-L1 therapy in melanoma by inhibiting the expression of recipient bacterial phospholipase C (PLC) and increases the accumulation of docosahexaenoic acid (DHA). An increased level of circulating DHA inhibits PD-L1 expression in tumor cells by binding the PD-L1 promoter and subsequently prevents c-myc-initiated transcription of PD-L1. Colonization of germ-free male mice with gut bacteria from anti-PD-L1 non-responding patients supplemented with DHA enhances the efficacy of anti-PD-L1 therapy compared to controls. Our findings reveal a previously unknown mechanistic impact of PNP on human tumor immunotherapy by modulating gut bacterial metabolic pathways.https://doi.org/10.1038/s41467-025-56498-2 |
| spellingShingle | Yun Teng Chao Luo Xiaolan Qiu Jingyao Mu Mukesh K. Sriwastva Qingbo Xu Minmin Liu Xin Hu Fangyi Xu Lifeng Zhang Juw Won Park Jae Yeon Hwang Maiying Kong Zhanxu Liu Xiang Zhang Raobo Xu Jun Yan Michael L. Merchant Craig J. McClain Huang-Ge Zhang Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolites Nature Communications |
| title | Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolites |
| title_full | Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolites |
| title_fullStr | Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolites |
| title_full_unstemmed | Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolites |
| title_short | Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolites |
| title_sort | plant nanoparticles enhance anti pd l1 efficacy by shaping human commensal microbiota metabolites |
| url | https://doi.org/10.1038/s41467-025-56498-2 |
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