Short-Chain Fatty Acid Production by Gut Microbiota Predicts Treatment Response in Multiple Myeloma

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dc.contributor.authorRodríguez-García, Alba
dc.contributor.authorArroyo Barea, Andrés
dc.contributor.authorGarcía-Vicente, Roberto
dc.contributor.authorMorales Fernández, María Luz
dc.contributor.authorGómez-Gordo, Rubén
dc.contributor.authorJusto Jiménez, Pablo
dc.contributor.authorCuéllar Pérez-Ávila, Clara
dc.contributor.authorSánchez-Pina, José
dc.contributor.authorLópez-Muñoz, Nieves
dc.contributor.authorAlonso Fernández, Rafael Alberto
dc.contributor.authorPuig Morón, Noemí
dc.contributor.authorMateos Moreno, María Victoria
dc.contributor.authorAyala Díaz, Rosa María
dc.contributor.authorGómez Garre, María Dulce Nombre
dc.contributor.authorMartínez López, Joaquín
dc.contributor.authorLinares Gómez, María
dc.date.accessioned2024-02-19T09:58:35Z
dc.date.available2024-02-19T09:58:35Z
dc.date.issued2023-12-18
dc.description.abstractPurpose: 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 positively associated 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.eng
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Ciencia, Innovación y Universidades (España)
dc.description.sponsorshipInstituto de Investigación Hospital 12 de Octubre
dc.description.sponsorshipCentro de Investigación Biomédica en Red Cáncer
dc.description.sponsorshipAsociación Española Contra el Cáncer
dc.description.sponsorshipSociedad Espanola de Hematología y Hemoterapia
dc.description.statuspub
dc.identifier.citationRodríguez-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.
dc.identifier.doi10.1158/1078-0432.ccr-23-0195
dc.identifier.issn1078-0432
dc.identifier.issn1557-3265
dc.identifier.officialurlhttps://doi.org/10.1158/1078-0432.ccr-23-0195
dc.identifier.urihttps://hdl.handle.net/20.500.14352/101539
dc.issue.number4
dc.journal.titleClinical Cancer Research
dc.language.isoeng
dc.page.final917
dc.page.initial904
dc.relation.projectIDinfo:eu-repo/grantAgreement/FPU19/04933
dc.relation.projectIDinfo:eu-repo/grantAgreement/PID2021-123056OA-I00
dc.relation.projectIDinfo:eu-repo/grantAgreement/IDEAS20014LINA
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu577.2
dc.subject.cdu577.1
dc.subject.keywordMieloma
dc.subject.keywordMicrobiota
dc.subject.keywordÁcidos grasos de cadena corta
dc.subject.ucmBioquímica (Farmacia)
dc.subject.ucmBiología molecular (Farmacia)
dc.subject.unesco24 Ciencias de la Vida
dc.titleShort-Chain Fatty Acid Production by Gut Microbiota Predicts Treatment Response in Multiple Myeloma
dc.typejournal article
dc.volume.number30
dspace.entity.typePublication
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relation.isAuthorOfPublicatione6f24d0a-7a49-49e1-8482-fd36f9fa1627
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relation.isAuthorOfPublication.latestForDiscovery9c913b09-6475-4ba1-9561-09ce64264416
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