Abstract
BackgroundProgression 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.MethodsHere, we used C57BL/6 J ApcMin/+ 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 human-into-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.ResultsWe report herein, YYFZBJS treatment blocked tumor initiation and progression in ApcMin/+ mice with less change of body weight and increased immune function. Moreover, diversity analysis of fecal samples demonstrated that YYFZBJS regulated animal’s natural gut flora, including Bacteroides fragilis, Lachnospiraceae and so on. Intestinal tumors from conventional and germ-free mice fed with stool from YYFZBJS volunteers had been decreased. Some inflammation’ expression also have been regulated by the gut microbiota mediated immune cells. Intestinal lymphatic, and mesenteric lymph nodes (MLN), accumulated CD4+ CD25+ Foxp3 positive Treg cells were reduced by YYFZBJS treatment in ApcMin/+ mice. Although YYFZBJS had no inhibition on CRC cell proliferation by itself, the altered Tregs mediated by YYFZBJS repressed CRC cancer cell growth, along with reduction of the phosphorylation of β-catenin.ConclusionsIn conclusion, we demonstrated that gut microbiota and Treg were involved in CRC development and progression, and we propose YYFZBJS as a new potential drug option for the treatment of CRC.6W2ydHZG-3mvoN8oBgCZVNVideo abstractGraphical abstract
Highlights
Progression of Colorectal cancer (CRC) is influenced by single or compounded environmental factors
YYFZBJS had no inhibition on CRC cell proliferation by itself, the altered T regulatory cells (Tregs) mediated by YYFZBJS repressed CRC cancer cell growth, along with reduction of the phosphorylation of β-catenin
In conclusion, we demonstrated that gut microbiota and Treg were involved in CRC development and progression, and we propose YYFZBJS as a new potential drug option for the treatment of CRC
Summary
Progression of Colorectal cancer (CRC) is influenced by single or compounded environmental factors. Accumulating evidence suggests that the gut microbiota, chronic inflammation, host genetic predisposition, and environmental factors have been linked with the progression of CRC [2]. Previous studies have identified several bacteria that can promote carcinogenesis by different mechanisms, such as Bacteroides, which can alter bile acid metabolism and/or increase IL-22 levels [3]; Fusobacterium nucleatum which can activate the autophagy pathway and alter colorectal cancer chemotherapeutic response through Toll-like receptor pathways [4] and Eschericia which can induce colonic infection in the bacterial mediated CRC [5]. The fecal samples of CRC patients can induce intestinal tumorigenesis and colon cell proliferation in colon tumour model mice, as well as increase the expression of inflammatory genes and carcinogenic factors [6]. Emerging studies have found significant differences in intestinal microbial communities between CRC patients and healthy individuals [7]
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