The Inhibitory Effect of Gut Microbiota and Its Metabolites on Colorectal Cancer

Abstract

CRC is the second leading cause of cancer-related death worldwide. There are about 700,000 people dying of CRC every year [1]. CRC is considered as one of the health care challenges, and it is related to genetic encoding and more significantly, about 70% of all CRC cases are influential by environmental aspects through a couple of years, including diets, lifestyle, metabolic syndrome and gut microecology, etc [2]. Gut microbiota consists mainly of bacteria, fungi, bacteria and viruses that populate the gut, primarily the large intestine. About 90% of gut microbiota is composed of two phyla, that is, Firmicutes and Bacteroidetes, in healthy human [3]. With the development of technology, we have a better understanding of the composition, function and metabolic characteristics of the human gut microbiota [4]. There is growing evidence that commensal bacteria of human being is the vital determinant of healthy or pathological conditions, including cancer [5]. Metagenomics and metabolomics researches stressed the double effect of the gut microbiota in tumorigenesis (either inhibit cancer or promote cancer) [6]. Gut microbiota exerts the significant effects on host by producing vitamins, metabolizing dietary compounds, inhibiting the expansion and systemic infiltration of gut pathogens [7]. Other results underline the complicacy and two-way of the association between microbiota and cancer. The progression of cancer may change the microbiota. Meanwhile, altering microbiota may influence cancer development [8]. Undoubtedly, the occurrence of CRC is also related to the function of some gut microbiota constituents whose role serves as initiator or inhibitor [9]. Although we have studied the association for many years, only a small part feature was exposed. In this essay, we will list some current results about cellular and microbial metabolism regulation in CRC, concentrating on the mechanistic association of gut microbiota metabolites and constituents with CRC prevention or treatment. The Mechanism of Gut Microbiota against Cancer Recently evidences from in vitro and animal model to clinical trials, as well as the use of selected gut microbiota for preventing or treating CRC, have demonstrated the antiproliferative activity. The selected gut microbiota mainly includes Lactobacillus, Bifidobacterium sp., Enterococcus faecalis and so on. Many studies based on human cancer cells or cell line demonstrated that gut microbiota processes the function of restraining cell proliferation or stimulating apoptosis in CRC (Table 1). In the main animal models studied from 2017 to 2019, N-methyl-Nnitrosourea (MNU), 1,2-dimethylhydrazine (DMH) and azoxymethane (AOM) were used as CRC inductor respectively. The specific gut microbiota studied in these models is shown in Table 2. In human studies conducted between 2015 and 2017, several double-blind, randomized and placebo controlled researches indicated that the addition of specific gut microbiota is effective in treating, which reduces the postoperative complications of CRC Colorectal cance...

Soluble peptidoglycan fragments produced by Limosilactobacillus fermentum with antiproliferative activity are suitable for potential therapeutic development: A preliminary report

“…Based on the microbiological outcomes, we further investigated the role of SPFs in an in vitro model of a human colorectal cancer HCT116 cell line. In this regard, recent scientific literature widely focuses on the anticancer properties exerted by gut microbiota against colorectal cancer ( Chen and Li, 2020 ; Sheikh et al, 2021 ). In particular, most of the clinical research between 2015 and 2017 shows the crucial role of specific gut microbiomes in postsurgical complications of colorectal cancer ( Aisu et al, 2015 ; Consoli et al, 2016 ; Theodoropoulos et al, 2016 ; Flesch et al, 2017 ; Hibberd et al, 2017 ) acting on immune system functionality and inflammation.…”

Interplay between Dysbiosis of Gut Microbiome, Lipid Metabolism, and Tumorigenesis: Can Gut Dysbiosis Stand as a Prognostic Marker in Cancer?

“…+ T cells into immunosuppressive Treg cells [81] Prevents the proliferation and induces the apoptosis of colon cancer cells through overexpression of p57 and Bax [82] It prevents the proliferation, angiogenesis, and metastasis of colorectal cancer through overexpression of sp1, mir-203, and p21/waf-1 and downregulating the expression of NRP-1 [83] Propionate Inhibits the growth of hepatocellular carcinoma [85] Prevents the cytokine-induced expression of VCAM-1 and ICAM-1 by blocking the NF-κB activity [86] Lactobacillus and Bifidobacterium are involved in the conversion of linoleic acid (LA) to conjugated linoleic acids (CLA) [75]. SCFAs such as acetate, propionate, and butyrate are produced by gut microbiota and are regarded as prime in the mechanism of lipid metabolism through an interaction between glucagon-like peptide-1 (GLP-1) and G proteincoupled cell surface receptors, such as GPR41 and GPR43 receptors, in the gut [76,77].…”

“…Propionate inhibits the growth of hepatocellular carcinoma [ 85 ] and cytokine-induced expression of VCAM-1 and ICAM-1 by blocking NF- κ B activity which enumerates potent anti-inflammatory potential. Lactobacillus and Bifidobacterium convert linoleic acid (LA) to conjugated linoleic acids (CLA), which induces programmed cell death through inhibition of PI3K/Akt and ERK signaling pathways [ 86 ] ( Table 3 ).…”

Exploring the Inflammatory Pathogenesis of Colorectal Cancer

“…Multiple strains of bacteria have been directly linked to colon cancer pathogenesis including Fusobacterium Nucleatum , Streptococcus gallolyticus , Bacteroides fragilis , E coli , Enterococcus faecalis [ 58 ]. Several recent review articles discuss different aspects of the microbiome as they relate to colon cancer such as biofilm formation, the microbiome’s impact on stem cells, the role of antibiotics and probiotics in CRC, and the study of “omics” as pertains to the microbiome, which are beyond the scope of this review [ 52 , 58 , 59 , 60 , 61 , 62 , 63 ]. Instead, we will primarily focus on the role of the microbiome on inflammatory and select metabolic pathways in the context of colorectal cancer.…”