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Nutrition and Cancer

A Synbiotic Combination of Resistant Starch and Bifidobacterium lactis Facilitates Apoptotic Deletion of Carcinogen-Damaged Cells in Rat Colon¹

Richard K. Le Leu², Ian L. Brown^*, Ying Hu, Anthony R. Bird, Michelle Jackson, Adrian Esterman^** and Graeme P. Young

Department of Medicine, Flinders University of South Australia, Bedford Park, South Australia 5042; ^* National Starch & Chemical Company, Bridgewater, NJ; CSIRO Health Sciences and Nutrition, Adelaide, South Australia; and ^** Flinders Centre for Epidemiology & Biostatistics, Flinders University, Bedford Park, South Australia 5042

²To whom correspondence should be addressed. E-mail: richard.leleu{at}flinders.edu.au.

Recent reports suggest that combinations of prebiotics and probiotics may be protective against colorectal cancer. We examined in rats the effects of probiotic bacteria, resistant starch (RS), and their interaction on luminal and epithelial events of relevance to the development of colorectal cancer. Lyophilized cultures (1 x 10¹⁰ cfu/g) of Lactobacillus acidophilus and/or Bifidobacterium lactis were added at a concentration of 1% by weight to a semipurified diet containing either low-RS (no supplemented RS) or moderate-RS (10% Hi-maize®) and fed to male Sprague-Dawley rats for 4 wk. Experimental end-points included cecal bacterial enumeration, fecal and cecal pH, SCFA levels, cell proliferation, and the acute apoptotic response to a genotoxic carcinogen (AARGC; measured 6 h after a single azoxymethane injection). A significant interaction between dietary RS and supplemental bacteria was observed for the AARGC in the colon and fecal pH (P < 0.01). Rats fed the moderate-RS diet in combination with B. lactis had a significantly greater AARGC in the colon than those fed that diet without B. lactis. Fecal pH was elevated in the moderate-RS fed rats supplemented with bacteria. The moderate-RS diet increased cell proliferation and crypt column height (P < 0.001) compared with the low-RS diet. SCFA levels and numbers of bifidobacteria and lactobacilli species were also increased (P < 0.001) by the moderate-RS diet, whereas pH levels and total coliforms were lowered (P < 0.001). The synbiotic combination of RS and B. lactis significantly facilitated the apoptotic response to a genotoxic carcinogen in the distal colon of rats. It appears likely that ingested RS acts as a metabolic substrate, thus creating the right conditions for B. lactis to exert its proapoptotic action. Because the synbiotic combination of these agents facilitates the apoptotic response to DNA damage by a cancer initiator in the colon of rats, it warrants further study for its capacity to protect against colorectal cancer.

KEY WORDS: • apoptosis • prebiotics • probiotics • butyrate • colon cancer

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