Journal Article

Network Analysis of Gut Microbiome and Metabolome to Discover Microbiota-Linked Biomarkers in Patients Affected by Non-Small Cell Lung Cancer

Gili, Tommaso, Del Chierico, Federica, Conta, Giorgia, Vernocchi, Pamela, Conte, Federica, Paci, Paola, Nuti, Marianna, Marchetti, Paolo, Botticelli, Andrea, Caldarelli, Guido, Miccheli, Alfredo, Putignani, Lorenza

2020

Overview

Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as Akkermansia muciniphila, Rikenellaceae, Bacteroides, Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients.

• Publisher: MDPI AG,MDPI
• Subject: Akkermansia - classification / Akkermansia - genetics / Akkermansia - isolation & purification / Alcohols - metabolism / Aldehydes - metabolism / Antineoplastic Agents, Immunological - therapeutic use / Bacteroides - classification / Bacteroides - genetics / Bacteroides - isolation & purification / Biomarkers / Cancer therapies / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - immunology / Carcinoma, Non-Small-Cell Lung - microbiology / Clostridiaceae - classification / Clostridiaceae - genetics / Clostridiaceae - isolation & purification / Databases, Genetic / Digestive system / Disease Progression / Drug Monitoring - methods / Fatty Acids, Volatile - metabolism / Gastrointestinal Microbiome - genetics / Gastrointestinal Microbiome - immunology / Gene Expression Regulation, Neoplastic / Gene Regulatory Networks / Gut microbiota / Humans / Immune checkpoint inhibitors / Immune system / Immunotherapy / Immunotherapy - methods / Indoles - metabolism / Lung cancer / Lung Neoplasms - drug therapy / Lung Neoplasms - genetics / Lung Neoplasms - immunology / Lung Neoplasms - microbiology / Metabolites / Metabolome - genetics / Metabolome - immunology / Metagenomics - methods / Microbiota / NMR / Nuclear magnetic resonance / Peptostreptococcus - classification / Peptostreptococcus - genetics / Peptostreptococcus - isolation & purification / Precision Medicine - methods / Programmed Cell Death 1 Receptor - antagonists & inhibitors / Programmed Cell Death 1 Receptor - genetics / Programmed Cell Death 1 Receptor - immunology / RNA, Ribosomal, 16S - genetics / Signal Transduction