Significant and conflicting correlation of IL-9 withPrevotellaandBacteroidesin human colorectal cancer

Abstract

20Background: Colorectal cancer (CRC) is a widespread disease that represents an example of chronic 21 inflammation-associated tumor. In fact, the immune system, besides protecting the host from 22Aim: The cellular and molecular characterization of the immune response and the evaluation of GM 33 composition in healthy and tumor mucosa, focusing on the correlation between cytokines' profile and 34 GM signature. 35 36 Methods: We collected tumoral (CRC) and healthy (CRC-S) mucosa samples of 45 CRC patients. 37 For each sample, we characterized the Tissue Infiltrating Lymphocytes (TIL)'s subset profile and the 38 GM composition. In addition, in 14 CRC patients, we evaluated the CRC and CRC-S molecular 39 inflammatory response (26 cytokines/chemokines) and we correlated this profile with GM 40 composition using the Dirichlet Multinomial Regression. 41 42Results: The analysis of T cells subsets distribution showed that CRC samples displayed higher 43 percentages of Th17, Th2, Tregs, Tc17, Tc1/Tc17, and Tcreg, compared to CRC-S. Notably, also the 44 number of Th9 was higher, even if not significantly, in CRC tissue compared to healthy one. In 45 addition, we found that MIP-1α, IL-1β, IL-2, IP-10, IL-6, IL-8, IL-17A, IFN-γ, TNF-α, MCP-1, IL-46 1α, P-selectin and IL-9 were significantly increased in CRC compared to CRC-S. Moreover, the GM 47 analysis revealed that CRC samples had significantly higher levels of Fusobacteria, Proteobacteria, 48Fusobacterium, Ruminococcus2 (Lachnospiraceae family) and Ruminococcus (Ruminococcaceae 49 family) than CRC-S. Finally, we found that the abundance of Prevotella spp in CRC samples was 50 negatively correlated with IL-17A and positively with IL-9. In addition, the abundance of Bacteroides 51and Escherichia/Shigella species in CRC samples showed a negative association with IL-9 and IP-10 52 respectively. 53 54 Conclusions: Our data show a clear dissimilarity of inflammatory profile and GM composition 55 between the tumor and the adjacent healthy tissue, displaying the generation of a peculiar CRC 56 microenvironment. Interestingly, relating the tissue cytokine profile with the GM composition, we 57 confirmed the presence of a bidirectional crosstalk between the immune response and the host's 58 commensal microorganisms; in detail, we documented for the first time that Prevotella spp. and 59 Bacteroides spp. are correlated (positively and negatively, respectively) with the IL-9, whose role in 60 CRC development is still debated. 61 62 63

Resolving the Paradox of Colon Cancer Through the Integration of Genetics, Immunology, and the Microbiota

“…Moreover, positive and negative correlations between intratumoral IL-9 and abundance of Prevotella or Bacteroides spp. were reported in CRC respectively ( 207 ).…”

Characterization of the “gut microbiota-immunity axis” and microbial lipid metabolites in atrophic and potential celiac disease

“…DNA extraction and bioinformatics analysis of 16S rRNA were performed as previously described (Niccolai et al, 2020), Briefly, total DNA was extracted from duodenal mucosa samples of aCD and pCD patients using the DNeasyPowerLyzerPowerSoil Kit (Qiagen, Hilden, Germany) from frozen samples (-80 • C) according to the manufacturer's instructions. The quality and quantity of extracted DNA were assessed using the Qubit Fluorometer (Thermo Fisher Scientific) and then genomic DNA was frozen at -20 • C.…”

Association between oral microbiome and seven types of cancers in East Asian population: a two-sample Mendelian randomization analysis

“…Furthermore, Prevotella, recognized as the second most abundant genus in the human oral microbiome, has inhibitory role in breast, stomach, and colorectal cancers in our MR analysis. In the published literature (Niccolai et al, 2020;Huh et al, 2022), the influence of Prevotella on cancer progression appears to be multifaceted, contingent upon the cancer type, its stage, the host's immunological profile, and different body sites. Emerging evidence delineates its potential anticancer properties, manifested through mechanisms such as the amplification of immune responses, attenuation of inflammation, or induction of cellular apoptosis.…”