Gegen Qinlian decoction enhances immunity and protects intestinal barrier function in colorectal cancer patients via gut microbiota.

ABSTRACT

BACKGROUND: We previously showed, using the Traditional Chinese Medicine System Pharmacology Database, that Gegen Qinlian decoction (GQD) had a direct antitumor effect, and was combined with programmed cell death protein (PD)-1 inhibitors to treat microsatellite stable (MSS) tumor-bearing mice. However, the effect of GQD on patients with colorectal cancer (CRC) is not clear. AIM: To determine the therapeutic mechanism of GQD in improving immune function, reducing inflammation and protecting intestinal barrier function. METHODS: Seventy patients with CRC were included in this study 37 in the control group and 33 in the treatment group. The proportions of CD4+ T, CD8+ T, natural killer (NK), NKT and T regulatory cells were measured by flow cytometry. Levels of the cytokines tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-6, IL-10 and serotonin (5-hydroxytryptamine; 5-HT) in serum were assessed by enzyme-linked immunosorbent assay (ELISA). The expression of zonula occludens (ZO)-1, occludin, nuclear factor (NF)-κB and TNF-α in tumor and normal tissues was measured by immunohistochemistry. The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis. RESULTS: There were no adverse events in the treatment group. The proportion of CD4+ T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups (P < 0.05). The level of TNF-α in the post-treatment group was significantly lower than that in the pre-treatment and control groups (P < 0.05). The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group (P < 0.05). The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group (P < 0.05). The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group (P = 0.010). Compared with the control group, expression of NF-κB and TNF-α in tumor tissues of the treatment group was significantly decreased (P < 0.05). Compared with the pre-treatment group, GQD decreased the relative abundance of Megamonas and Veillonella. In addition, GQD increased the relative abundance of Bacteroides, Akkermansia and Prevotella. CONCLUSION: GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.