Distinct Gut Microbiome and Metabolome Profiles Associate with Differential Responses to Immunotherapy in Colorectal

Fang Liang1, Jing Li1,2,3, Yingkun Yue1

  • 11Department of Oncology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.

Insights

Gut microbiome and metabolites impact immunotherapy success in advanced colorectal cancer (CRC). Specific microbial and metabolic profiles predict response, offering potential for personalized treatment strategies.

Area of Science:

  • Oncology
  • Microbiome Research
  • Immunotherapy

Background:

  • Intestinal microbiome composition influences immune checkpoint inhibitor (ICI) efficacy.
  • Understanding gut microbiota and metabolic profiles is crucial for optimizing immunotherapy in colorectal cancer (CRC).

Purpose of the Study:

  • To investigate associations between gut microbiota, metabolic profiles, and clinical outcomes in advanced MSI-H CRC patients treated with immunotherapy.
  • To identify potential predictive biomarkers for immunotherapy response in CRC.

Main Methods:

  • Fecal metagenomic sequencing and untargeted metabolomics were performed on 20 advanced CRC patients undergoing immunotherapy.
  • Patients were categorized into clinical benefit response (CBR) and non-benefit (NCB) groups based on treatment efficacy.

Main Results:

  • The CBR group showed enrichment of 's_Clostridium unclassified' and specific metabolites (guanosine, quercetin derivative).
  • The NCB group exhibited enrichment of 's_Roseburia hominis', 's_Marseilla massiliensis', and different metabolites (pyrophosphate, riboflavin).
  • Distinct 'flora-metabolite' interactions correlated with immunotherapy outcomes were identified.

Conclusions:

  • Specific gut microbial and metabolic profiles can serve as predictive biomarkers for immunotherapy response in advanced CRC.
  • These findings provide a foundation for developing individualized immunotherapy strategies through microecological modulation.