Effect of prebiotics on biomarkers of colorectal cancer in humans: a systematic review Michelle J Clark, Kim Robien, and Joanne L Slavin Prebiotics may prevent colorectal cancer (CRC) development in humans by modifying the composition or activity of the colorectal microflora. Epidemiologic and animal studies have shown a reduction in CRC or CRC biomarkers after the administration of prebiotics. Studies using indirect chemical biomarkers of CRC in humans, however, gave mixed results. Recently, human studies measuring direct physical indices of CRC risk after prebiotic consumption have been published. The purpose of this review is to summarize those studies to provide recommendations for the use of prebiotics in CRC risk reduction. A PubMed search was conducted, revealing nine studies. One tested lactulose, two evaluated a blend of oligofructose and inulin, and six measured resistant starch. Lactulose reduced adenoma recurrence, while resistant starch had no effect on adenoma or CRC development. Crypt mitotic location, gene expression, and DNA methylation were somewhat improved after resistant starch consumption. No changes in cell proliferation and apoptosis, crypt morphology, or aberrant crypt foci were found. More human studies measuring physical changes to the gut are needed. © 2012 International Life Sciences Institute INTRODUCTION Colorectal (CRC) cancer was the third most common cancer in the United States in 2010. In addition, the mor- tality rate of CRC was the second highest of any cancer. 1 While cancer treatments have made large strides in recent decades, chemoprevention by diet and other lifestyle factors offers a more desirable alternative.Various dietary interventions have been examined for their effectiveness in preventing cancer, but there is still much work to be done. 2 Diet-cancer interactions are made even more complex in the colon and rectum by the microflora, which has unique effects on the colorectal environment. The human gut contains hundreds of bacterial species, of which the genera Bacteroides and Bifidobacte- rium comprise approximately 50%. The relationship between the composition of the intestinal microflora and CRC in humans is just beginning to be explored. The microflora may contribute to either prevention or pro- motion of colorectal carcinogenesis by way of mutagenic degradation products, colonocyte proliferation, stool fre- quency, inflammation and immunity, toxification of pro- carcinogens by bacterial enzymes, or prevention of pathogenic organism overgrowth. 3,4 The differences in microflora composition between subjects with colon or rectal cancer or adenomas and subjects with normal colonoscopies have recently been investigated in cross- sectional studies, which showed conflicting results. 5–7 The abundance of Bacteroides spp. was significantly greater in cases versus controls in one study 5 and significantly lower in another, 6 while a third found different effects from various Bacteroides spp. 7 The third study also found a reduction in butyrate-producing bacteria and an increase in opportunistic pathogens in CRC subjects. 7 In other studies, Bifidobacterium and Lactobacillus, thought to be beneficial bacterial genera, were found to have anticancer properties, 8–10 but research on their role in preventing human CRC when given as probiotic supplements is Affiliations: MJ Clark and JL Slavin are with the Department of Food Science and Nutrition, University of Minnesota, Saint Paul, Minnesota, USA. K Robien is with the Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA. Correspondence: J Slavin, Department of Food Science and Nutrition, University of Minnesota, 225 FScN, 1334 Eckles Avenue, Saint Paul, MN 55108, USA. E-mail: jslavin@umn.edu. Phone: +1-612-624-7234. Fax: +1-612-625-5272. Key words: colorectal neoplasms, humans, prebiotics, systematic review Special Article doi:10.1111/j.1753-4887.2012.00495.x Nutrition Reviews® Vol. 70(8):436–443 436