Wenzi Jiedu Recipe ameliorates colorectal cancer by remodeling the gut microbiota and tumor microenvironment

Abstract

IntroductionWenzi Jiedu Recipe (WJR), traditional Chinese medicine (TCM) formula, has been proven to be clinically useful in the treatment of colorectal cancer (CRC). However, its underlying mechanisms are still elusive, which limits its wider application. Thus, we aimed to evaluate the effect of WJR on CRC and elucidate mechanisms underlying its action.MethodsNetwork pharmacology was employed to clarify the “herb-active ingredient-target” network of WJR. The 16S rDNA sequencing method was used to analyze the changes of gut microbes mediated by WJR in tumor-bearing mice with CRC. The proportions of CD4+ T cell and CD8+ T cell were measured by flow cytometry. Levels of the cytokines interleukin (IL)-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were assessed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA).ResultsWJR showed significant anti-CRC effects both in vitro and in vivo. Network pharmacology revealed that WJR exerts anti-CRC therapeutic effect on multiple targets and signaling pathways. Gut microbiota analysis revealed that WJR therapy significantly enriched for Oscillibacter and Bacteroides_acidifacien. In particular, we found that WJR significantly increased the proportion of CD8+ T cells and the expression of immune-associated cytokines IL-10, IFN-γ, and TNF-α.ConclusionThe regulation of gut microbiota by WJR may be the breakthrough point to clarify its mechanism of action in the treatment of CRC, and it has a good prospect of clinical application.

Akkermansia muciniphila and herbal medicine in immune-related diseases: current evidence and future perspectives

“…The 16S rDNA sequencing method was used to analyze the changes of gut microbes revealed that WJR significantly enriched for Oscillibacter and Bacteroides_acidifacien in tumor-bearing mice with colorectal cancer. Meanwhile, WJR significantly increased the proportion of CD8+ T cells and the expression of immuneassociated cytokines IL-10, IFN-g, and TNF-a (Qiu et al, 2022). The above studies suggest that traditional Chinese medicine can improve tumor immunotherapy by adjusting the intestinal microecological structure.…”

Integrated gut microbiota and metabolome analysis reveals the mechanism of Xiaoai Jiedu recipe in ameliorating colorectal cancer

“…After administrating with different agents, we collected the mice feces for gut microbiota analyses( 14 ). The stool DNA was extracted using the E.Z.N.A.…”

“…TCM can play an anti-tumor role by regulating the intestinal flora structure ( 12 , 13 ). In the previous study, we found that Wenzi Jiedu Recipe (WJR) could effectively inhibit the development of CRC by regulating the structure of gut microbiota via enriching Oscillibacter and Bacteroides_acidifacien ( 14 ).…”

Influence of gut microecology in the development of malignant tumors and its potential therapeutic application: A review

“…For example, Wenzi Jiedu prescription, a TCM prescription, has been proven to have clinical application value in the treatment of colorectal cancer. As Qiu WL et al [101] found that Wenzi Jiedu prescription had an obvious effect on anticolorectal cancer in vivo and in vitro. Subsequently, the team used network pharmacology to show that it could exert antitumor effect through an approach of “multi-target, multi-pathway.” And according to the analysis of gut microbial flora, this prescription can significantly enrich the tracer to Eubacterium and Bacteroides.…”