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

• Published in: Journal of translational medicine Vol. 18; no. 1; p. 49
• Main Authors: Botticelli, Andrea, Vernocchi, Pamela, Marini, Federico, Quagliariello, Andrea, Cerbelli, Bruna, Reddel, Sofia, Del Chierico, Federica, Di Pietro, Francesca, Giusti, Raffaele, Tomassini, Alberta, Giampaoli, Ottavia, Miccheli, Alfredo, Zizzari, Ilaria Grazia, Nuti, Marianna, Putignani, Lorenza, Marchetti, Paolo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.02.2020; BioMed Central; BMC
• Subjects: Atezolizumab; Biomarkers; Carcinoma, Non-Small-Cell Lung - drug therapy; Care and treatment; Clinical trials; Composition; Criminal investigation; Deoxyribonucleic acid; Disease; Diseases; DNA; Esters; Fatty acids; Feces; Gastrointestinal Microbiome; Health aspects; Humans; Immune checkpoint inhibitors; Immunotherapy; Intestinal microflora; Lung cancer; Lung Neoplasms - drug therapy; Lysine; Melanoma; Metabolic pathways; Metabolism; Metabolites; Metabolomics; Methods; Microbiota; Microbiota (Symbiotic organisms); Monoclonal antibodies; Niacin; Nicotinic acid; Nivolumab; NMR; Non-small cell lung cancer; Non-small cell lung carcinoma; Nuclear magnetic resonance; Patient outcomes; Patients; PD-1 protein; Pembrolizumab; Propionic acid; Retirement benefits; Small cell lung cancer; Small cell lung carcinoma; Solid phase methods; Targeted cancer therapy; Italy; United States > US
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-020-02231-0

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. 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 H-NMR in order to detect volatile and non-volatile metabolites. Metabolomic data were processed by statistical profiling and chemometric analyses. 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. 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.