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Area of Science:

  • Microbiome research
  • Gastroenterology
  • Oncology

Background:

  • The gut microbiome's role in colorectal cancer (CRC) pathogenesis is not fully understood.
  • Human CRC-derived Clostridioides difficile strains induce tumorigenesis in mouse models.
  • C. difficile's contribution to human CRC requires further investigation.

Purpose of the Study:

  • To investigate the hypothesis that C. difficile contributes to human CRC pathogenesis.
  • To determine if C. difficile is enriched in CRC tumors compared to paired normal tissues.

Main Methods:

  • Analysis of matched tumor/normal tissue samples from 108 individuals undergoing CRC resection in Kuala Lumpur, Malaysia.
  • Assessment of C. difficile prevalence using 16S rRNA amplicon sequencing, culture, and PCR.
  • High-resolution taxonomic assignment for precise bacterial identification.

Main Results:

  • C. difficile detection was prevalent (38% of individuals) but present in low abundance in tumors (median 0.01%).
  • C. difficile detection was significantly higher in biofilm-positive tumor tissues (81%) compared to biofilm-negative.
  • Exploratory analyses revealed distinct taxonomic and functional pathway differences between C. difficile-positive and -negative groups.

Conclusions:

  • C. difficile is frequently detected in the tumor microbiome of colorectal cancer patients.
  • Despite low abundance, C. difficile may significantly impact the tumor microbiome's composition and function.
  • Further research is warranted to elucidate C. difficile's precise role in CRC development and progression.