Alba Rodríguez-García, Raquel Ancos-Pintado, Roberto García-Vicente, Alejandra Ortiz-Ruiz, Andrés Arroyo, Miguel Ángel Navarro, María Luz Morales, Patricia Guevara-Ramirez, Pablo Justo, Nieves López-Muñoz, José Sánchez-Pina, Rafael Alonso, María Victoria Selma, María Dolores Frutos-Lisón, Rocío García-Villalba, Francisco A Tomás-Barberán, Rosa Ayala, Joaquín Martínez-López, María Linares
{"title":"单克隆淋巴瘤和多发性骨髓瘤治疗中的微生物群衍生尿石素 A。","authors":"Alba Rodríguez-García, Raquel Ancos-Pintado, Roberto García-Vicente, Alejandra Ortiz-Ruiz, Andrés Arroyo, Miguel Ángel Navarro, María Luz Morales, Patricia Guevara-Ramirez, Pablo Justo, Nieves López-Muñoz, José Sánchez-Pina, Rafael Alonso, María Victoria Selma, María Dolores Frutos-Lisón, Rocío García-Villalba, Francisco A Tomás-Barberán, Rosa Ayala, Joaquín Martínez-López, María Linares","doi":"10.1186/s40168-025-02045-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Gut microbiota-derived urolithins may influence multiple myeloma (MM) disease progression and treatment. We analyzed urolithins and their associated microbiota in a retrospective cohort of 45 patients with active MM or premalignant disease using mass spectrometry and 16S rRNA gene sequencing.</p><p><strong>Results: </strong>Patients with detectable levels of urolithin in serum and stool and a higher abundance of urolithin-related microbiota had a better outcome. Analysis of the effects of urolithin A (UroA) treatment ex vivo, in vitro, and in vivo revealed that UroA is cytotoxic against MM cell lines and modulates the cell cycle and mitochondrial activity. Notably, UroA inhibits the proliferation of primary MM cells in vitro and in a xenograft mouse model, improving overall survival. Finally, combination therapy with UroA and bortezomib has a synergistic effect in vitro, even in the presence of bortezomib resistance, and modulates signaling pathways involved in MM development.</p><p><strong>Conclusions: </strong>UroA might be a potential therapeutic agent to halt MM disease progression or to overcome resistance when used in combination. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"13 1","pages":"56"},"PeriodicalIF":14.9000,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869585/pdf/","citationCount":"0","resultStr":"{\"title\":\"Microbiota-derived urolithin A in monoclonal gammopathies and multiple myeloma therapy.\",\"authors\":\"Alba Rodríguez-García, Raquel Ancos-Pintado, Roberto García-Vicente, Alejandra Ortiz-Ruiz, Andrés Arroyo, Miguel Ángel Navarro, María Luz Morales, Patricia Guevara-Ramirez, Pablo Justo, Nieves López-Muñoz, José Sánchez-Pina, Rafael Alonso, María Victoria Selma, María Dolores Frutos-Lisón, Rocío García-Villalba, Francisco A Tomás-Barberán, Rosa Ayala, Joaquín Martínez-López, María Linares\",\"doi\":\"10.1186/s40168-025-02045-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Gut microbiota-derived urolithins may influence multiple myeloma (MM) disease progression and treatment. We analyzed urolithins and their associated microbiota in a retrospective cohort of 45 patients with active MM or premalignant disease using mass spectrometry and 16S rRNA gene sequencing.</p><p><strong>Results: </strong>Patients with detectable levels of urolithin in serum and stool and a higher abundance of urolithin-related microbiota had a better outcome. Analysis of the effects of urolithin A (UroA) treatment ex vivo, in vitro, and in vivo revealed that UroA is cytotoxic against MM cell lines and modulates the cell cycle and mitochondrial activity. Notably, UroA inhibits the proliferation of primary MM cells in vitro and in a xenograft mouse model, improving overall survival. Finally, combination therapy with UroA and bortezomib has a synergistic effect in vitro, even in the presence of bortezomib resistance, and modulates signaling pathways involved in MM development.</p><p><strong>Conclusions: </strong>UroA might be a potential therapeutic agent to halt MM disease progression or to overcome resistance when used in combination. Video Abstract.</p>\",\"PeriodicalId\":18447,\"journal\":{\"name\":\"Microbiome\",\"volume\":\"13 1\",\"pages\":\"56\"},\"PeriodicalIF\":14.9000,\"publicationDate\":\"2025-02-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869585/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microbiome\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s40168-025-02045-6\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbiome","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s40168-025-02045-6","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Microbiota-derived urolithin A in monoclonal gammopathies and multiple myeloma therapy.
Background: Gut microbiota-derived urolithins may influence multiple myeloma (MM) disease progression and treatment. We analyzed urolithins and their associated microbiota in a retrospective cohort of 45 patients with active MM or premalignant disease using mass spectrometry and 16S rRNA gene sequencing.
Results: Patients with detectable levels of urolithin in serum and stool and a higher abundance of urolithin-related microbiota had a better outcome. Analysis of the effects of urolithin A (UroA) treatment ex vivo, in vitro, and in vivo revealed that UroA is cytotoxic against MM cell lines and modulates the cell cycle and mitochondrial activity. Notably, UroA inhibits the proliferation of primary MM cells in vitro and in a xenograft mouse model, improving overall survival. Finally, combination therapy with UroA and bortezomib has a synergistic effect in vitro, even in the presence of bortezomib resistance, and modulates signaling pathways involved in MM development.
Conclusions: UroA might be a potential therapeutic agent to halt MM disease progression or to overcome resistance when used in combination. Video Abstract.
期刊介绍：
Microbiome is a journal that focuses on studies of microbiomes in humans, animals, plants, and the environment. It covers both natural and manipulated microbiomes, such as those in agriculture. The journal is interested in research that uses meta-omics approaches or novel bioinformatics tools and emphasizes the community/host interaction and structure-function relationship within the microbiome. Studies that go beyond descriptive omics surveys and include experimental or theoretical approaches will be considered for publication. The journal also encourages research that establishes cause and effect relationships and supports proposed microbiome functions. However, studies of individual microbial isolates/species without exploring their impact on the host or the complex microbiome structures and functions will not be considered for publication. Microbiome is indexed in BIOSIS, Current Contents, DOAJ, Embase, MEDLINE, PubMed, PubMed Central, and Science Citations Index Expanded.
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