YYFZBJS ameliorates colorectal cancer progression in ApcMin/+ mice by remodeling gut microbiota and inhibiting regulatory T-cell generation

Abstract

Background: Progression of Colorectal cancer (CRC) is influenced by single or compounded environmental factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. T cell, one of the main populations of effector immune cells in antitumor immunity, has been considered as a double-edged sword during the progression of CRC. Our previous studies indicate that traditional Chinese herbs (TCM) have potential anticancer effects in improving quality of life and therapeutic effect. However, little is known about the mechanism of TCM formula in cancer prevention. Methods: Here, we used C57BL/6 J Apc Min/+ mice, an animal model of human intestinal tumorigenesis, to investigate the gut bacterial diversity and their mechanisms of action in gastrointestinal adenomas, and to evaluate the effects of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) on of colon carcinogenesis in vivo and in vitro. Through humaninto-mice fecal microbiota transplantation (FMT) experiments from YYFZBJS volunteers or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration.

YYFZBJS Inhibits Colorectal Tumorigenesis by Remodeling Enterotoxigenic Bacteroides Fragilis Mediated M2 Macrophage Polarization in Vivo and in Vitro

“…Several recent studies have con rmed the link between dysbiosis of the gut microbiome and colorectal cancer [35,36]. Our previous ndings have con rmed that, ETBF, one of the most regulated monomers by YYFZBJS, promoted the proliferation of tumor cells through immunity [5]. However, no studies investigating the impact of TCM on the balance between gut microbiome and immune cell in the colonic tumorigenesis have been reported.…”

“…However, the development of CRC remains to be completely understood owing to its complexity. Recently, accumulating evidence suggests that the gut microbiota, chronic in ammation, host genetic predisposition, and environmental factors have been linked with the progression of CRC [3,4] We have demonstrated that enterotoxigenic Bacteroides fragilis (ETBF) strains secrete the B. fragilis toxin, severely altered Tregs mediated by YYFZBJS repressed CRC cancer cell growth, along with reduction of the phosphorylation of β-catenin [5].…”

“…The whole intestine was removed immediately after sacri ce and opened longitudinally after washed with ice-cold phosphate buffer saline (PBS) as previously described [5]. The number, location, and size of visible tumors throughout the intestine were measured to calculate the incidence of adenoma.…”

“…As shown in Fig. 1A, the intragastric administration of YYFZBJS-L/M/H were taken at the doses of 3.825 g/kg, 7.65 g/kg and 15.3 g/kg according to HED (human equivalent dose) [5,28]. YYFZBJS-L/M/H and Aspirin (30 mg/kg) were given orally for 9 weeks during the DSS treatment separately as previously described (1).…”

“…However, few chemotherapeutic drugs are available, and such drugs have signi cant toxic side effects that can severely impair the immune system and hematopoietic system [24][25][26]. Our previous studies have shown that Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) volunteers altered dysregulated in ammation and oncogenic pathways and inhibited intestinal tumorigenesis [5].…”