RT Journal Article
T1 Short-Chain Fatty Acid Production by Gut Microbiota Predicts Treatment Response in Multiple Myeloma
A1 Rodríguez-García, Alba
A1 Arroyo Barea, Andrés
A1 García-Vicente, Roberto
A1 Morales Fernández, María Luz
A1 Gómez-Gordo, Rubén
A1 Justo Jiménez, Pablo
A1 Cuéllar Pérez-Ávila, Clara
A1 Sánchez-Pina, José
A1 López-Muñoz, Nieves
A1 Alonso Fernández, Rafael Alberto
A1 Puig Morón, Noemí
A1 Mateos Moreno, María Victoria
A1 Ayala Díaz, Rosa María
A1 Gómez Garre, María Dulce Nombre
A1 Martínez López, Joaquín
A1 Linares Gómez, María
AB Purpose: The gut microbiota plays important roles in health and disease. We questioned whether the gut microbiota and related metabolites are altered in monoclonal gammopathies and evaluated their potential role in multiple myeloma and its response to treatment.Experimental Design: We used 16S rRNA sequencing to characterize and compare the gut microbiota of patients with monoclonal gammopathy of undetermined significance (n ¼ 11), smoldering  multiple myeloma (n ¼ 9), newly diagnosed multiple myeloma (n ¼ 11), relapsed/refractory multiple myeloma (n ¼ 6), or with complete remission (n ¼ 9). Short-chain fatty acids (SCFA) were quantified in serum and tested in cell lines. Relevant metabolites were validated in a second cohort of 62 patients.Results: Significant differences in alpha- and beta diversity were present across the groups and both were lower in patients with relapse/refractory disease and higher in patients with complete remission after treatment. Differences were found in the abundance of several microbiota taxa across disease progression and in response to treatment. Bacteria involved in SCFA production, including Prevotella, Blautia, Weissella, and  agathobacter, were more represented in the premalignant or complete remission samples, and patients with higher levels of Agathobacter showed better overall survival. Serum levels of butyrate and propionate decreased across disease progression and butyrate was positivelyassociated with a better response. Both metabolites had antiproliferative effects in multiple myeloma cell lines. Conclusions: We demonstrate that SCFAs metabolites and the gut microbiota associated with their production might have beneficial effects in disease evolution and response to treatment, underscoring its therapeutic potential and value as a predictor.
SN 1078-0432
SN 1557-3265
YR 2023
FD 2023-12-18
LK https://hdl.handle.net/20.500.14352/101539
UL https://hdl.handle.net/20.500.14352/101539
LA eng
NO Rodríguez-García, Alba, et al. «Short-Chain Fatty Acid Production by Gut Microbiota Predicts Treatment Response in Multiple Myeloma». Clinical Cancer Research, enero de 2024, pp. OF1-14. DOI.org (Crossref), https://doi.org/10.1158/1078-0432.CCR-23-0195.
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Instituto de Investigación Hospital 12 de Octubre
NO Centro de Investigación Biomédica en Red Cáncer
NO Asociación Española Contra el Cáncer
NO Sociedad Espanola de Hematología y Hemoterapia
DS Docta Complutense
RD 18 jul 2024