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.

Significant and Conflicting Correlation of IL-9 With Prevotella and Bacteroides in Human Colorectal Cancer / Niccolai E.; Russo E.; Baldi S.; Ricci F.; Nannini G.; Pedone M.; Stingo F.C.; Taddei A.; Ringressi M.N.; Bechi P.; Mengoni A.; Fani R.; Bacci G.; Fagorzi C.; Chiellini C.; Prisco D.; Ramazzotti M.; Amedei A.. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - ELETTRONICO. - 11:(2021), pp. 1-14. [10.3389/fimmu.2020.573158]

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

Niccolai E.;Russo E.;Baldi S.;Ricci F.;Nannini G.;Pedone M.;Stingo F. C.;Taddei A.;Ringressi M. N.;Bechi P.;Mengoni A.;Fani R.;Bacci G.;Fagorzi C.;Chiellini C.;Prisco D.;Ramazzotti M.;Amedei A.
2021

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.
2021
11
1
14
Niccolai E.; Russo E.; Baldi S.; Ricci F.; Nannini G.; Pedone M.; Stingo F.C.; Taddei A.; Ringressi M.N.; Bechi P.; Mengoni A.; Fani R.; Bacci G.; Fagorzi C.; Chiellini C.; Prisco D.; Ramazzotti M.; Amedei A.
File in questo prodotto:
File Dimensione Formato  
Niccolai et al - Frontiers in Immunology 2021 - CRC.pdf

accesso aperto

Descrizione: Niccolai et al - 2021 - Frontiers in Immunology
Tipologia: Pdf editoriale (Version of record)
Licenza: Tutti i diritti riservati
Dimensione 1.58 MB
Formato Adobe PDF
1.58 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1227599
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 36
  • ???jsp.display-item.citation.isi??? 35
social impact