Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment

Abstract Background Despite the efficacy of immune checkpoint inhibitors (ICIs) only the 20–30% of treated patients present long term benefits. The metabolic changes occurring in the gut microbiota metabolome are herein proposed as a factor potentially influencing the response to immunotherapy. Meth...

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Main Authors: Andrea Botticelli, Pamela Vernocchi, Federico Marini, Andrea Quagliariello, Bruna Cerbelli, Sofia Reddel, Federica Del Chierico, Francesca Di Pietro, Raffaele Giusti, Alberta Tomassini, Ottavia Giampaoli, Alfredo Miccheli, Ilaria Grazia Zizzari, Marianna Nuti, Lorenza Putignani, Paolo Marchetti
Format: Article
Language:English
Published: BMC 2020-02-01
Series:Journal of Translational Medicine
Online Access:https://doi.org/10.1186/s12967-020-02231-0
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author Andrea Botticelli
Pamela Vernocchi
Federico Marini
Andrea Quagliariello
Bruna Cerbelli
Sofia Reddel
Federica Del Chierico
Francesca Di Pietro
Raffaele Giusti
Alberta Tomassini
Ottavia Giampaoli
Alfredo Miccheli
Ilaria Grazia Zizzari
Marianna Nuti
Lorenza Putignani
Paolo Marchetti
author_facet Andrea Botticelli
Pamela Vernocchi
Federico Marini
Andrea Quagliariello
Bruna Cerbelli
Sofia Reddel
Federica Del Chierico
Francesca Di Pietro
Raffaele Giusti
Alberta Tomassini
Ottavia Giampaoli
Alfredo Miccheli
Ilaria Grazia Zizzari
Marianna Nuti
Lorenza Putignani
Paolo Marchetti
author_sort Andrea Botticelli
collection DOAJ
description Abstract Background Despite the efficacy of immune checkpoint inhibitors (ICIs) only the 20–30% of treated patients present long term benefits. The metabolic changes occurring in the gut microbiota metabolome are herein proposed as a factor potentially influencing the response to immunotherapy. Methods The metabolomic profiling of gut microbiota was characterized in 11 patients affected by non-small cell lung cancer (NSCLC) treated with nivolumab in second-line treatment with anti-PD-1 nivolumab. The metabolomics analyses were performed by GC–MS/SPME and 1H-NMR in order to detect volatile and non-volatile metabolites. Metabolomic data were processed by statistical profiling and chemometric analyses. Results Four out of 11 patients (36%) presented early progression, while the remaining 7 out of 11 (64%) presented disease progression after 12 months. 2-Pentanone (ketone) and tridecane (alkane) were significantly associated with early progression, and on the contrary short chain fatty acids (SCFAs) (i.e., propionate, butyrate), lysine and nicotinic acid were significantly associated with long-term beneficial effects. Conclusions Our preliminary data suggest a significant role of gut microbiota metabolic pathways in affecting response to immunotherapy. The metabolic approach could be a promising strategy to contribute to the personalized management of cancer patients by the identification of microbiota-linked “indicators” of early progressor and long responder patients.
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spelling doaj.art-99b3dbdf2f344f43b6e4967bf2f8b4672022-12-21T22:46:24ZengBMCJournal of Translational Medicine1479-58762020-02-0118111010.1186/s12967-020-02231-0Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatmentAndrea Botticelli0Pamela Vernocchi1Federico Marini2Andrea Quagliariello3Bruna Cerbelli4Sofia Reddel5Federica Del Chierico6Francesca Di Pietro7Raffaele Giusti8Alberta Tomassini9Ottavia Giampaoli10Alfredo Miccheli11Ilaria Grazia Zizzari12Marianna Nuti13Lorenza Putignani14Paolo Marchetti15Department of Clinical and Molecular Medicine, Sapienza University of RomeUnit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCSDepartment of Chemistry, Sapienza University of RomeUnit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCSDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of RomeUnit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCSUnit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCSAOU Sant’Andrea HospitalAOU Sant’Andrea HospitalDepartment of Chemistry, Sapienza University of RomeDepartment of Chemistry, Sapienza University of RomeNMR-based Metabolomics Laboratory, Sapienza University of RomeDepartment of Experimental Medicine, University SapienzaDepartment of Experimental Medicine, University SapienzaUnit of Parasitology and Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCSDepartment of Clinical and Molecular Medicine, Sapienza University of RomeAbstract Background Despite the efficacy of immune checkpoint inhibitors (ICIs) only the 20–30% of treated patients present long term benefits. The metabolic changes occurring in the gut microbiota metabolome are herein proposed as a factor potentially influencing the response to immunotherapy. Methods The metabolomic profiling of gut microbiota was characterized in 11 patients affected by non-small cell lung cancer (NSCLC) treated with nivolumab in second-line treatment with anti-PD-1 nivolumab. The metabolomics analyses were performed by GC–MS/SPME and 1H-NMR in order to detect volatile and non-volatile metabolites. Metabolomic data were processed by statistical profiling and chemometric analyses. Results Four out of 11 patients (36%) presented early progression, while the remaining 7 out of 11 (64%) presented disease progression after 12 months. 2-Pentanone (ketone) and tridecane (alkane) were significantly associated with early progression, and on the contrary short chain fatty acids (SCFAs) (i.e., propionate, butyrate), lysine and nicotinic acid were significantly associated with long-term beneficial effects. Conclusions Our preliminary data suggest a significant role of gut microbiota metabolic pathways in affecting response to immunotherapy. The metabolic approach could be a promising strategy to contribute to the personalized management of cancer patients by the identification of microbiota-linked “indicators” of early progressor and long responder patients.https://doi.org/10.1186/s12967-020-02231-0
spellingShingle Andrea Botticelli
Pamela Vernocchi
Federico Marini
Andrea Quagliariello
Bruna Cerbelli
Sofia Reddel
Federica Del Chierico
Francesca Di Pietro
Raffaele Giusti
Alberta Tomassini
Ottavia Giampaoli
Alfredo Miccheli
Ilaria Grazia Zizzari
Marianna Nuti
Lorenza Putignani
Paolo Marchetti
Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment
Journal of Translational Medicine
title Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment
title_full Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment
title_fullStr Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment
title_full_unstemmed Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment
title_short Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment
title_sort gut metabolomics profiling of non small cell lung cancer nsclc patients under immunotherapy treatment
url https://doi.org/10.1186/s12967-020-02231-0
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