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 sequen...

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Detalhes bibliográficos
Autores: Rodríguez-García, Alba, Ancos-Pintado, Raquel, García-Vicente, Roberto, Ortiz-Ruiz, Alejandra, Arroyo, Andrés, Navarro, Miguel Ángel, Morales, María Luz, Guevara-Ramirez, Patricia, Justo, Pablo, López-Muñoz, Nieves, Sánchez-Pina, José, Alonso, Rafael, Selma, María Victoria, Frutos-Lisón, María Dolores, García-Villalba, Rocío, Tomás-Barberán, Francisco A., Ayala Díaz, Rosa María, Martínez López, Joaquín, Linares Gómez, María
Tipo de documento: artigo
Data de publicação:2025
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositório:Docta Complutense
Idioma:inglês
OAI Identifier:oai:docta.ucm.es:20.500.14352/129136
Acesso em linha:https://hdl.handle.net/20.500.14352/129136
Access Level:Acceso aberto
Palavra-chave:612.015
577.1
577.2
Multiple myeloma
Gut microbiota
Urolithin
Metabolites
Bioquímica (Farmacia)
Biología molecular (Farmacia)
2302 Bioquímica
2302.21 Biología Molecular
Descrição
Resumo: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.

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