Probiotic metabolites as epigenetic targets in the prevention of colon cancer Manoj Kumar, Ravinder Nagpal, Vinod Verma, Ashok Kumar, Navrinder Kaur, Rajkumar Hemalatha, Sanjeev K. Gautam, and Birbal Singh Dietary interventions for preventing colon cancer have recently attracted increased attention from researchers and clinicians. The probiotics have emerged as poten- tial therapeutic agents but are also regarded as healthy dietary supplements for nutrition and health applications. The probiotic metabolome may interfere with various cellular and molecular processes, including the onset and progression of colon cancer. Probiotic metabolites may lead to the modulation of diverse cellular signal transduction and metabolic pathways. The gut microbial metabolites (organic acids, bacteriocins, peptides, etc.) have been noted to interact with multiple key targets in various metabolic pathways that regulate cellular pro- liferation, differentiation, apoptosis, inflammation, angiogenesis, and metastasis. Progress in this field suggests that epigenetic alterations will be widely used in the near future to manage colon cancer. The present review provides insights into the molecular basis of the therapeutic applications and the chemopreventive activities of certain probiotic metabolites, with emphasis on the interaction between these metabolites and the molecular signaling cascades that are considered to be epigenetic targets in preventing colon cancer. © 2012 International Life Sciences Institute INTRODUCTION Probiotics, the live microbial food supplements with the ability to beneficially affect the gut microbiome, have long been known to augment a variety of immunological and metabolic parameters through diverse mechanisms. 1 The following mechanisms are among those that are well defined: altering composition of already existing normal microbial ecosystem, maintaining gut lumen epithelial barrier functions, and modulating mucosal and systemic immune responses of the host (Figure 1). 2–5 The probiot- ics recommended for human applications are primarily the two classes of lactic-acid-producing microorganisms, the bifidobacteria (e.g., Bifidobacterium longum, Bifido- bacterium infantis, and Bifidobacterium adolescentis) and the low-GC-content lactic acid bacteria such as Entero- coccus spp., Lactobacillus spp., Lactococcus spp., Leuconos- toc spp., Pediococcus spp., and Streptococcus spp. 6–9 Many of these bacteria are also normal symbionts of mamma- lian (human and animal) and other vertebrates’ intestine and are already in use as probiotics or direct-fed micro- bial agents and starter cultures. In particular, the Lacto- bacillus spp. are ubiquitously present in fermented foods, vegetation, the oral cavity, the gastrointestinal (GI) Affiliations: M Kumar and R Hemalatha are with the Department of Microbiology and Immunology, National Institute of Nutrition, Hyderabad, India. R Nagpal is with the Department of Biotechnology, SUS College of Research and Technology, Mohali, India. V Verma is with the Research and Development Centre, National Heart Centre, Singapore. A Kumar is with the Department of Zoology, MLK Post Graduate College, Balrampur, India. N Kaur is with the Division of Cancer Therapeutics, Institute of Cell and Molecular Biology, Singapore. SK Gautam is with the Department of Biotechnology, Kurukshetra University, Kurukshetra, India. B Singh is with the Indian Veterinary Research Institute, Regional Station Palampur, India. Correspondence: M Kumar, Department of Microbiology & Immunology, National Institute of Nutrition, Hyderabad – 500007, India. E-mail: manoj15micro@yahoo.co.in. B Singh, Indian Veterinary Research Institute, Regional Station Palampur – 176,061, India. E-mail: bsbpalampur@yahoo.co.in. Phone: +91-9418431715 (cell). Fax: +91-1894233063. Key words: colon cancer, epigenetic alterations, probiotic metabolites Special Article doi:10.1111/j.1753-4887.2012.00542.x Nutrition Reviews® Vol. 71(1):23–34 23