Role of Traditional Chinese Medicine Syndrome Type, Gut Microbiome, and Host Immunity in Predicting Early and Advanced Stage Colorectal Cancer

Abstract

Objective: To investigate the role of Traditional Chinese Medicine (TCM) syndrome type, gut microbiome distribution, and host immunity function in predicting the early and advanced clinical stages of colorectal cancer (CRC). Methods: A cross-sectional case-control study was performed which included 48 early stage and 48 advanced patients with CRC enrolled from March 2018 to December 2020. 16S rRNA gene sequencing was performed to analyze the gut microbiomes of the patients, while T and B lymphocyte subsets in peripheral blood were assessed using flow cytometry. TCM syndrome type was measured using the spleen deficiency syndrome (SDS) scale. Results: The abundance levels of Prevotella, Escherichia-Shigella, and Faecalibacterium in the gut microbiota were significantly increased in the advanced group, while Bacteroides was significantly decreased. Phascolarctobacterium was detectable only in the early metaphase group, whereas Alistipes was detectable only in the advanced group. The lymphocyte ( P = .006), T helper cell (TH) ( P = .002), cytotoxic T cell (TC) ( P = .003), double positive T cell (DPT) ( P = .02), and total T counts ( P = .001) were significantly higher in the early metaphase group than in the advanced metaphase group. Compared with patients with early stage CRC, the advanced group had a higher SDS score. After adjusting for clinical stage, Spearman’s correlation analysis showed interactions among gut microbiome abundance, T cell level, and SDS score. Multivariate logistic analysis showed that after controlling for the SDS score, abundance of Alistipes and Faecalibacterium, and double negative T cell (DNT) level, DPT was significantly associated with a lower risk of advanced-stage disease (hazard ratio, 0.918; P = .022). Conclusion: Our study suggested associations between clinical stage, SDS, gut microbiota, and T lymphocytes, which provided insights for a potential prediction model for the disease progression of CRC.