Probiotic metabolites as epigenetic targets in the prevention of colon cancer

Article (PDF Available)inNutrition Reviews 71(1):23-34 · January 2013with298 Reads
DOI: 10.1111/j.1753-4887.2012.00542.x · Source: PubMed
Dietary interventions for preventing colon cancer have recently attracted increased attention from researchers and clinicians. The probiotics have emerged as potential 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 proliferation, 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.

Full-text (PDF)

Available from: Manoj Kumar, Oct 02, 2014
    • "The results obtained with bacterial lysates from lot 512058 were similar to those obtained with lot 507132 of " newfound " VSL#3. Accordingly with previous reports which showed the ability of some probiotics to exert antitumor effects through different potential mechanisms [20][21][22][23], both " original " and " newfound " VSL#3 lysate samples at 10 mg/ml were able to significantly reduce after 48 h the number of viable cells in the analyzed tumor cell lines, thus confirming their ability to induce both inhibition of proliferation and cell death. However, in these experimental conditions, the inhibition of viable cell number increase observed after treatment with " newfound " VSL#3 was significantly lower when compared to that observed with the " original " product for all used cell lines. "
    [Show abstract] [Hide abstract] ABSTRACT: A careful selection of the probiotic agent, standardization of the dose and detailed characterization of the beneficial effects are essential when considering use of a probiotic for the dietary management of serious diseases. However, changes in the manufacturing processes, equipment or facilities can result in differences in the product itself due to the live nature of probiotics. The need to reconfirm safety and/or efficacy for any probiotic product made at a different factory is therefore mandatory. Recently, under the brand VSL#3®, a formulation produced by a manufacturer different from the previous one, has been commercialized in some European countries (the UK and Holland). VSL#3 is a high concentration multi-strain preparation which has been recognized by the main Gastroenterology Associations for the dietary management of pouchitis as well as ulcerative colitis. We have compared the “original” VSL#3 produced in USA with the “newfound” VSL#3 produced in Italy. According to our results, the “newfound” VSL#3 has 130–150% more “dead bacteria” compared to the “original” product, raising concerns for the well-known association between dead microbes with adverse effects. The abilities of bacterial lysates from the two formulations to influence in vitro viability and proliferation of different tumor cell lines also resulted different. The repair of previously scratched monolayers of various adherent tumor cell lines (i.e. HT1080, and Caco-2 cells) was inhibited more significantly by the “original” VSL#3 when compared to the “newfound” VSL#3. Tumor cell cycle profile, in particular cell cycle arrest and apoptotic death of the cancer cells, further confirms that the “original” VSL#3 has a better functional profile than the “newfound” VSL#3, at least in in vitro. Our data stress the importance of the production conditions for the “newfound” VSL#3 considering that this product is intended to be used for the dietary management of patients with very serious diseases, such as chronic inflammatory bowel diseases.
    Full-text · Article · Sep 2016
    • "Probiotics have multiple therapeutic advantages, playing significant roles in decreasing the mutagenicity of the epithelial layer, as reported in various experimental models of colorectal cancer [56]. In-depth investigations have shown that the relationship between colorectal cancer and probiotics seems to be primarily dependent on bioactive metabolites of probiotic bacteria, which lead to the generation of therapeutic anti-carcinogenic compounds [89]. Certain probiotic microorganisms and their extractions demonstrate growth inhibitory activities on adenocarcinoma cell lines. "
    [Show abstract] [Hide abstract] ABSTRACT: Bifidobacterium bifidum BGN4 is a probiotic strain that has been used as a major ingredient to produce nutraceutical products and as a dairy starter since 2000. The various bio-functional effects and potential for industrial application of B. bifidum BGN4 has been characterized and proven by in vitro (i.e., phytochemical bio-catalysis, cell adhesion and anti-carcinogenic effects on cell lines, and immunomodulatory effects on immune cells), in vivo (i.e., suppressed allergic responses in mouse model and anti-inflammatory bowel disease), and clinical studies (eczema in infants and adults with irritable bowel syndrome). Recently, the investigation of the genome sequencing was finished and this data potentially clarifies the biochemical characteristics of B. bifidum BGN4 that possibly illustrate its nutraceutical functionality. However, further systematic research should be continued to gain insight for academic and industrial applications so that the use of B. bifidum BGN4 could be expanded to result in greater benefit. This review deals with multiple studies on B. bifidum BGN4 to offer a greater understanding as a probiotic microorganism available in functional food ingredients. In particular, this work considers the potential for commercial application, physiological characterization and exploitation of B. bifidum BGN4 as a whole.
    Full-text · Article · Sep 2016
    • "The plausible mechanism by which probiotic GS4 inhibited HDAC activity needs further explanation. It is apparent from the current study that probiotic GS4 has the ability to modulate gut microbiota, which subsequently elevates the fermentation of carbohydrates ultimately leading to the production of health beneficial metabolites, which are known to target HDAC activity (Kumar et al., 2013; Wang et al., 2012 ), but this very fine-tuning mechanism needs to be intensified. Some of the previous studies from our laboratory have already highlighted the important properties of the probiotic strain GS4, such as antioxidative (Sukumar & Ghosh, 2011), biohydrogenation ability to produce CLA (Dubey et al., 2012), ability to survive gastrointestinal transit (Bagad, Pande, & Ghosh, 2012 ) and modulation of the gut microflora as well reinstating the intestinal structural and functional integrity during colon carcinogenesis (Dubey et al., 2015). "
    [Show abstract] [Hide abstract] ABSTRACT: Probiotic Pediococcus pentosaceus GS4 produces conjugated linoleic acid (CLA) through biohydrogenation, which may be vital for colon cancer mitigation. Here, we have appraised the anti-cancer potential of probiotic GS4 against colon cancer. CLA produced by probiotic GS4 reduced the proliferation of HCT-116 in vitro rendering towards apoptosis and subsequently abrogated NF-κB and p-Akt. Probiotic GS4 efficiently mitigated colon cancer in azoxymethane (AOM)-induced colon cancer mice model, which was evident from reduced disease severity, alleviated oxidative stress and neoplastic characters. Further delineation of underlying consequences at the level of host–microbe interface, the probiotic GS4 arbitrated the gut microflora-associated biohydrogenation, which subsequently triggered apoptosis in colonocytes, apparent from PARP cleavage, caspase 3 activity, DNA fragmentation and inhibition of HDAC activity. Conclusively, modulation of host–microbe interface with selective colonizing strategies combined with unique biohydrogenation ability of probiotic GS4 promises to be a therapeutic/functional food supplement responsible for mitigation of colon cancer.
    Full-text · Article · Feb 2016
Show more