Literature DB >> 33488574

Significant and Conflicting Correlation of IL-9 With Prevotella and Bacteroides in Human Colorectal Cancer.

Elena Niccolai1, Edda Russo1, Simone Baldi1, Federica Ricci2, Giulia Nannini1, Matteo Pedone3, Francesco Claudio Stingo3, Antonio Taddei1, Maria Novella Ringressi1, Paolo Bechi1, Alessio Mengoni4, Renato Fani4, Giovanni Bacci4, Camilla Fagorzi4, Carolina Chiellini4, Domenico Prisco1,5, Matteo Ramazzotti2, Amedeo Amedei1,5.   

Abstract

Background and aim: Gut microbiota (GM) can support colorectal cancer (CRC) progression by modulating immune responses through the production of both immunostimulatory and/or immunosuppressive cytokines. The role of IL-9 is paradigmatic because it can either promote tumor progression in hematological malignancies or inhibit tumorigenesis in solid cancers. Therefore, we investigate the microbiota-immunity axis in healthy and tumor mucosa, focusing on the correlation between cytokine profile and GM signature.
Methods: In this observational study, we collected tumor (CRC) and healthy (CRC-S) mucosa samples from 45 CRC patients, who were undergoing surgery in 2018 at the Careggi University Hospital (Florence, Italy). First, we characterized the tissue infiltrating lymphocyte subset profile and the GM composition. Subsequently, we evaluated the CRC and CRC-S molecular inflammatory response and correlated this profile with GM composition, using Dirichlet multinomial regression.
Results: CRC samples displayed higher percentages of Th17, Th2, and Tregs. Moreover, CRC tissues showed significantly higher levels of MIP-1α, IL-1α, IL-1β, IL-2, IP-10, IL-6, IL-8, IL-17A, IFN-γ, TNF-α, MCP-1, P-selectin, and IL-9. Compared to CRC-S, CRC samples also showed significantly higher levels of the following genera: Fusobacteria, Proteobacteria, Fusobacterium, Ruminococcus2, and Ruminococcus. Finally, the abundance of Prevotella spp. in CRC samples negatively correlated with IL-17A and positively with IL-9. On the contrary, Bacteroides spp. presence negatively correlated with IL-9. Conclusions: Our data consolidate antitumor immunity impairment and the presence of a distinct microbiota profile in the tumor microenvironment compared with the healthy mucosa counterpart. Relating the CRC cytokine profile with GM composition, we confirm the presence of bidirectional crosstalk between the immune response and the host's commensal microorganisms. Indeed, we document, for the first time, that Prevotella spp. and Bacteroides spp. are, respectively, positively and negatively correlated with IL-9, whose role in CRC development is still under debate.
Copyright © 2021 Niccolai, Russo, Baldi, Ricci, Nannini, Pedone, Stingo, Taddei, Ringressi, Bechi, Mengoni, Fani, Bacci, Fagorzi, Chiellini, Prisco, Ramazzotti and Amedei.

Entities:  

Keywords:  T cells; colorectal cancer; cytokines; gut microbiota; immune response

Year:  2021        PMID: 33488574      PMCID: PMC7820867          DOI: 10.3389/fimmu.2020.573158

Source DB:  PubMed          Journal:  Front Immunol        ISSN: 1664-3224            Impact factor:   7.561


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