Biofilms and core pathogens shape the tumor microenvironment and immune phenotype in colorectal cancer

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Extensive research has explored the role of gut microbiota in colorectal cancer (CRC). Nonetheless, metatranscriptomic studies investigating the in situ functional implications of host-microbe interactions in CRC are scarce. Therefore, we characterized the influence of CRC core pathogens and biofilms on the tumor microenvironment (TME) in 40 CRC, paired normal, and healthy tissue biopsies using fluorescence in situ hybridization (FISH) and dual-RNA sequencing. FISH revealed that Fusobacterium spp. was associated with increased bacterial biomass and inflammatory response in CRC samples. Dual-RNA sequencing demonstrated increased expression of pro-inflammatory cytokines, defensins, matrix-metalloproteases, and immunomodulatory factors in CRC samples with high bacterial activity. In addition, bacterial activity correlated with the infiltration of several immune cell subtypes, including M2 macrophages and regulatory T-cells in CRC samples. Specifically, Bacteroides fragilis and Fusobacterium nucleatum correlated with the infiltration of neutrophils and CD4+ T-cells, respectively. The collective bacterial activity/biomass appeared to exert a more significant influence on the TME than core pathogens, underscoring the intricate interplay between gut microbiota and CRC. These results emphasize how biofilms and core pathogens shape the immune phenotype and TME in CRC while highlighting the need to extend the bacterial scope beyond CRC pathogens to advance our understanding and identify treatment targets.

Original languageEnglish
Article number2350156
JournalGut Microbes
Volume16
Issue number1
ISSN1949-0976
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.

    Research areas

  • Bacteroides fragilis, biofilms, Colorectal cancer (CRC), Fusobacterium nucleatum, in situ hybridization, fluorescence, sequence analysis, RNA

ID: 392584233