Dietary Sodium Gluconate Protects Rats from Large Bowel Cancer by Stimulating Butyrate Production

Abstract

Butyrate has an antitumorigenic effect on colorectal cancer cell lines. Dietary sodium gluconate (GNA) promotes butyrate production in the large intestine. Accordingly, we examined the effect of dietary GNA on tumorigenesis in the large intestine in rats. Male Fisher-344 rats (n = 32) were divided into 4 groups: 2 diets (with or without 50 g GNA/kg basal diet) x 2 treatments (with or without carcinogen administration). Colonic tumors were induced by 3 intraperitoneal injections of azoxymethane (15 mg/kg body wt, 1 time/wk) and dietary deoxycholic acid (2 g/kg basal diet). The experiment was conducted for 33 wk except for a few rats. Ingestion of GNA increased cecal butyrate concentration at the end of experiment (P < 0.01). No tumor development occurred in the untreated groups. Ingestion of GNA decreased the incidence of tumors in rats administered the carcinogen (37.5 vs. 100%, P < 0.05). Ingestion of GNA also decreased the mean number of tumors per rat (0.5 +/- 0.8 vs. 2.8 +/- 1.5, P < 0.01). beta-Catenin accumulation and TdT-mediated dUTP nick end labeling (TUNEL) positive cells in tumors were histochemically examined. The results of this study suggested that the antitumorigenic effect of GNA may involve the stimulation of apoptosis through enhanced butyrate production in the large intestine.

Mouse Intestine Selects Nonmotile flhDC Mutants of Escherichia coli MG1655 with Increased Colonizing Ability and Better Utilization of Carbon Sources

“…However, in the present study, we have shown that diet may play a role in minimizing colonization resistance as long as a specific preferred nutrient is not completely absorbed in the small intestine. That is, although it has been shown that the source of gluconate for E. coli colonization is the mouse intestinal tissue and not mouse chow (44), increasing the gluconate concentration in the intestine was possible since as much as 70% of the gluconate fed to animals reaches the cecum (20). Under these conditions, with 20 g/liter gluconate in the drinking water, small numbers of MG1655 bacteria were able to grow to high numbers in the presence of high numbers of …”

Evidence for Contributions of Gut Microbiota to Colorectal Carcinogenesis

“…In rodent models, administration of both butyrateproducing bacteria and butyrate metabolic precursors has been shown to increase colonic levels of butyrate and decrease precancerous lesions correlating with increased splenic NK cells and decreased β-glucuronidase activities in fecal cultures, both of which associated with protection against CRC [67,101]. Butyrate also promotes apoptosis through the Wnt signaling pathway in CRC cell lines [102].…”

Oral Administration of a Heat-Killed Cell Preparation ofEnterococcus faecalisStrain EC-12 Stimulates the Gene Expression of Na+–K+–2Cl−Co-Transporter 1 in Rat Ileal Epithelial Cells

“…The basal diet of this experiment consisted of (g/kg) -cornstarch, 637; casein, 200; soybean oil, 50; cellulose powder (Oriental Yeast Co., Ltd., Yokohama, Japan), 50; mineral mixture, 50; vitamin mixture, 10; and DLmethionine, 3. Both the mineral and vitamin mixtures had an identical composition to that of Kameue et al 10) and were purchased from Oriental Yeast Co., Ltd. (Yokohama, Japan).…”