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Gut Microbiota Dynamics during Chemotherapy in Epithelial Ovarian Cancer Patients Are Related to Therapeutic Outcome

SIMPLE SUMMARY: This pilot study on the trajectory of the gut microbiota (GM) in patients with epithelial ovarian cancer undergoing neoadjuvant and adjuvant chemotherapy highlighted peculiar dynamics associated with the therapeutic outcome. In particular, platinum-resistant patients showed a marked...

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Autores principales: D’Amico, Federica, Perrone, Anna Myriam, Rampelli, Simone, Coluccelli, Sara, Barone, Monica, Ravegnini, Gloria, Fabbrini, Marco, Brigidi, Patrizia, De Iaco, Pierandrea, Turroni, Silvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393652/
https://www.ncbi.nlm.nih.gov/pubmed/34439153
http://dx.doi.org/10.3390/cancers13163999
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author D’Amico, Federica
Perrone, Anna Myriam
Rampelli, Simone
Coluccelli, Sara
Barone, Monica
Ravegnini, Gloria
Fabbrini, Marco
Brigidi, Patrizia
De Iaco, Pierandrea
Turroni, Silvia
author_facet D’Amico, Federica
Perrone, Anna Myriam
Rampelli, Simone
Coluccelli, Sara
Barone, Monica
Ravegnini, Gloria
Fabbrini, Marco
Brigidi, Patrizia
De Iaco, Pierandrea
Turroni, Silvia
author_sort D’Amico, Federica
collection PubMed
description SIMPLE SUMMARY: This pilot study on the trajectory of the gut microbiota (GM) in patients with epithelial ovarian cancer undergoing neoadjuvant and adjuvant chemotherapy highlighted peculiar dynamics associated with the therapeutic outcome. In particular, platinum-resistant patients showed a marked temporal reduction in GM diversity and increased instability with loss of health-associated taxa and increased proportions of lactate-producing microorganisms compared to those sensitive to platinum. These potential GM signatures of therapeutic failure are detectable within the first half of chemotherapy cycles, suggesting that early integrated treatments also aimed at modulating GM could influence therapeutic outcome. Further studies in larger cohorts combining multiple omics and possibly animal models are urgently needed for in-depth mechanistic understanding. ABSTRACT: Epithelial ovarian cancer (EOC) is one of the most lethal and silent gynecological tumors. Despite appropriate surgery and chemotherapy, relapse occurs in over half of patients with a poor prognosis. Recently, the gut microbiota (GM) was hypothesized to influence the efficacy of anticancer therapies, but no data are available in EOC. Here, by 16S rRNA gene sequencing and inferred metagenomics, we profiled the GM of EOC patients at diagnosis and reconstructed its trajectory along the course of neoadjuvant or adjuvant chemotherapy up to follow-up. Compared to healthy subjects, the GM of EOC patients appeared unbalanced and severely affected by chemotherapy. Strikingly, discriminating patterns were identified in relation to the therapeutic response. Platinum-resistant patients showed a marked temporal reduction in GM diversity and increased instability with loss of health-associated taxa and increased proportions of Coriobacteriaceae and Bifidobacterium. Notably, most of these microorganisms are lactate producers, suggesting increased lactate production as supported by inferred metagenomics. In contrast, the GM of platinum-sensitive patients appeared overall more diverse and stable and enriched in lactate utilizers from the Veillonellaceae family. In conclusion, we identified potential GM signatures of therapeutic outcome in EOC patients, which could open up new opportunities for cancer prognosis and treatment.
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spelling pubmed-83936522021-08-28 Gut Microbiota Dynamics during Chemotherapy in Epithelial Ovarian Cancer Patients Are Related to Therapeutic Outcome D’Amico, Federica Perrone, Anna Myriam Rampelli, Simone Coluccelli, Sara Barone, Monica Ravegnini, Gloria Fabbrini, Marco Brigidi, Patrizia De Iaco, Pierandrea Turroni, Silvia Cancers (Basel) Article SIMPLE SUMMARY: This pilot study on the trajectory of the gut microbiota (GM) in patients with epithelial ovarian cancer undergoing neoadjuvant and adjuvant chemotherapy highlighted peculiar dynamics associated with the therapeutic outcome. In particular, platinum-resistant patients showed a marked temporal reduction in GM diversity and increased instability with loss of health-associated taxa and increased proportions of lactate-producing microorganisms compared to those sensitive to platinum. These potential GM signatures of therapeutic failure are detectable within the first half of chemotherapy cycles, suggesting that early integrated treatments also aimed at modulating GM could influence therapeutic outcome. Further studies in larger cohorts combining multiple omics and possibly animal models are urgently needed for in-depth mechanistic understanding. ABSTRACT: Epithelial ovarian cancer (EOC) is one of the most lethal and silent gynecological tumors. Despite appropriate surgery and chemotherapy, relapse occurs in over half of patients with a poor prognosis. Recently, the gut microbiota (GM) was hypothesized to influence the efficacy of anticancer therapies, but no data are available in EOC. Here, by 16S rRNA gene sequencing and inferred metagenomics, we profiled the GM of EOC patients at diagnosis and reconstructed its trajectory along the course of neoadjuvant or adjuvant chemotherapy up to follow-up. Compared to healthy subjects, the GM of EOC patients appeared unbalanced and severely affected by chemotherapy. Strikingly, discriminating patterns were identified in relation to the therapeutic response. Platinum-resistant patients showed a marked temporal reduction in GM diversity and increased instability with loss of health-associated taxa and increased proportions of Coriobacteriaceae and Bifidobacterium. Notably, most of these microorganisms are lactate producers, suggesting increased lactate production as supported by inferred metagenomics. In contrast, the GM of platinum-sensitive patients appeared overall more diverse and stable and enriched in lactate utilizers from the Veillonellaceae family. In conclusion, we identified potential GM signatures of therapeutic outcome in EOC patients, which could open up new opportunities for cancer prognosis and treatment. MDPI 2021-08-08 /pmc/articles/PMC8393652/ /pubmed/34439153 http://dx.doi.org/10.3390/cancers13163999 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
D’Amico, Federica
Perrone, Anna Myriam
Rampelli, Simone
Coluccelli, Sara
Barone, Monica
Ravegnini, Gloria
Fabbrini, Marco
Brigidi, Patrizia
De Iaco, Pierandrea
Turroni, Silvia
Gut Microbiota Dynamics during Chemotherapy in Epithelial Ovarian Cancer Patients Are Related to Therapeutic Outcome
title Gut Microbiota Dynamics during Chemotherapy in Epithelial Ovarian Cancer Patients Are Related to Therapeutic Outcome
title_full Gut Microbiota Dynamics during Chemotherapy in Epithelial Ovarian Cancer Patients Are Related to Therapeutic Outcome
title_fullStr Gut Microbiota Dynamics during Chemotherapy in Epithelial Ovarian Cancer Patients Are Related to Therapeutic Outcome
title_full_unstemmed Gut Microbiota Dynamics during Chemotherapy in Epithelial Ovarian Cancer Patients Are Related to Therapeutic Outcome
title_short Gut Microbiota Dynamics during Chemotherapy in Epithelial Ovarian Cancer Patients Are Related to Therapeutic Outcome
title_sort gut microbiota dynamics during chemotherapy in epithelial ovarian cancer patients are related to therapeutic outcome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393652/
https://www.ncbi.nlm.nih.gov/pubmed/34439153
http://dx.doi.org/10.3390/cancers13163999
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