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

A. Botticelli, P. Vernocchi, F. Marini, A. Quagliariello, B. Cerbelli, S. Reddel, F. Del Chierico, F. Di Pietro, R. Giusti, A. Tomassini, O. Giampaoli, A. Miccheli, I.G. Zizzari, M. Nuti, L. Putignani, P. Marchetti

Research output: Contribution to journalArticlepeer-review

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. © 2020 The Author(s).
Original languageEnglish
JournalJ. Transl. Med.
Volume18
Issue number1
DOIs
Publication statusPublished - 2020

Keywords

  • butyric acid
  • ketone
  • lysine
  • nicotinic acid
  • nivolumab
  • propionic acid
  • short chain fatty acid
  • tridecane
  • tumor marker
  • adult
  • aged
  • Article
  • cancer diagnosis
  • cancer growth
  • cancer immunotherapy
  • cancer patient
  • cancer survival
  • chemometric analysis
  • clinical article
  • clinical feature
  • cohort analysis
  • female
  • human
  • intestine flora
  • male
  • mass fragmentography
  • metabolic fingerprinting
  • metabolome
  • metabolomics
  • metagenomics
  • non small cell lung cancer
  • nonhuman
  • overall survival
  • prediction
  • progression free survival
  • proton nuclear magnetic resonance
  • solid phase microextraction
  • treatment response

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