Network analysis of gut microbiome and metabolome to discover microbiota-linked biomarkers in patients affected by non-small cell lung cancer

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number8730
Pages (from-to)1-19
Number of pages19
JournalInternational Journal of Molecular Sciences
Volume21
Issue number22
DOIs
Publication statusPublished - Nov 2 2020

Keywords

  • Anti-PD1 immune checkpoint inhibitor
  • Betweenness centrality
  • Clustering coefficient
  • Communities
  • Gut microbiome
  • Metabolite
  • Network analysis
  • Non-small cell lung cancer (NSCLC)
  • Operational taxonomic unit (OTU)
  • Weighted gene co-expression network analysis (WGCNA)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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