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Review
. 2018 Jun 15;9(14):2510-2517.
doi: 10.7150/jca.25324. eCollection 2018.

Effects of the intestinal microbial metabolite butyrate on the development of colorectal cancer

Xinqiang Wu  1 , Yuanbing Wu  2 , Liangmei He  3 , Longhuo Wu  4 , Xiangcai Wang  3 , Zhiping Liu  5   6
Affiliations
Review

Effects of the intestinal microbial metabolite butyrate on the development of colorectal cancer

Xinqiang Wu et al. J Cancer. .

Abstract

Colorectal cancer (CRC) is one of the major health threats in developed countries. Changes in dietary components, such as more protein and lipid intake, can increase the risk of CRC. Diet affects CRC in many ways. They regulate the composition and function of gut microbiota, which have an amazing metabolic capacity and can produce short chain fatty acids (SCFAs), such as propionate, acetate, and butyrate. Butyrate is a principal energy source for colonic epithelial cells and plays an important role in maintaining the stability of gut microbiota and the integrity of intestinal epithelium. However, there are few studies reviewing the anti-CRC potentials of butyrate. This review summarizes the recent research progresses in the effect of gut microbiota imbalance and the decrease in intestinal microbial metabolite butyrate caused by unbalanced diet on CRC development, and discusses the mechanisms of butyrate-induced anti-CRC activities, which may guide people to prevent CRC by improving diet structures.

Keywords: Butyrate; Colorectal cancer; Diet.; Gut microbiota.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Effect of balanced diet on intestinal health. In a balanced diet, food is mainly digested by digestive enzymes and bile acids from liver in the small intestine, and more than 90% are absorbed in the small intestine. After absorption, nutrients are distributed throughout the body through the circulation of the blood, in which monosaccharides, disaccharides, amino acids, fatty acids, vitamins and minerals play important roles in maintaining the health of the body. When dietary residues flow through the colon, they are broken down by intestinal microbiota, which produce short chain fatty acids, such as butyrate. Butyrate is a principal energy source for the gut microbiota and intestinal epithelial cells, and plays an important role in maintaining the stability of gut microbiota and the integrity of intestinal epithelia. Notably, butyrate can also inhibit cell proliferation, induce cell differentiation, promote cell apoptosis, and reduce tumor cell invasiveness to exert its anti-tumor properties, thus playing an important role in the health of the colon.
Figure 2
Figure 2
The mechanisms that butyrate suppresses CRC development. Fermentation of fiber in the lumen leads to production of short-chain fatty acids including butyrate. Butyrate can inhibit the development of CRC and promote intestinal health through various mechanisms. For example, butyrate can decrease the NRP-1 expression by inhibiting the transactivation of Sp1 to suppress the angiogenesis, metastasis and survival of CRC cells, and butyrate can promote the apoptosis of CRC cells by hyper-activating Wnt signaling pathway. In addition, butyrate can restrict cell proliferation, colony formation, cell invasion, and induce cell apoptosis in CRC cells through upregulating the expression of miR-203, P21waf1 and bax, and promoting endocan expression. Meanwhile, butyrate can increase p57 mRNA and protein levels by inhibiting c-Myc expression, which reduces miR-17-92a cluster transcription and the level of miR-92a. Collectively, the interactions between butyrate, NRP-1, Wnt, endocan, P21waf1 and bax, miR-203 and miR-92a mediate the anti-proliferation and pro-apoptosis effect of butyrate in CRC cells.
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