Disturbance of the intestinal microbiota balance may result in a shortage of beneficial bacteria and an excess of pathogens (dysbiosis). National Library of Medicine Anti-obesity and satiety factor? Colonoscopy uses a long, flexible and slender tube attached to a video camera and . These aspects can lead to different results and make it challenging to compare the results from such studies. One promising application for the treatment of colorectal cancer is the human microbiota manipulation, and as a consequence, the use of selective probiotics. Probiotics may have influence on the other mutagenic and carcinogenic factors, thus contribute to the prevention of cancer. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Short-chain fatty acids (SCFA) are organic acids consisting of 16 carbon atoms in the aliphatic chain, including acetic, propionic, butyric, valeric and caproic acid. Appleyard C.B., Cruz M.L., Isidro A.A., Arthur J.C., Jobin C., De Simone C. Pretreatment with the probiotic VSL#3 delays transition from inflammation to dysplasia in a rat model of colitis-associated cancer. As a lipophilic compound in undissociated form, it can penetrate the lipid cell membrane. demonstrated that probiotic induced apoptosis in gastric cancer cells (KATO3) by inhibiting NF-B and mTOR-mediated signaling [108]. Role of Microbiome in Carcinogenesis Process and Epigenetic Regulation of Colorectal Cancer. This ability is due to the presence and activity of some enzymes, such as azoreductase, -glucuronidase, -glucosidase, nitrate reductase, all of which are capable of converting heterocyclic aromatic amines, polycyclic aromatic hydrocarbons, and primary bile acids into active carcinogens and synthetize aglycones, ammonia, cresols, phenols and N-nitroso compounds [79]. Preoperative probiotics decrease postoperative infectious complications of colorectal cancer. Another study [21] showed how a specific strain of Lactobacillus plantarum inhibited colon cancer in the mouse model after the chemical induction of cancer. SCFAs are the main and final products of the metabolism of light-living bacteria large intestine [93]. Bacteriocins can cause: a portion of the bacterial cytoplasmic membrane that leads to the dissipation of the transmembrane potential and induces the leakage of K + ions, ATP and amino acids from the cytoplasm of attacked cells; cell lysis and interfering or inhibiting the synthesis of DNA, RNA and proteins (act as DNAase or RNAase) [88,89]. Rafter J., Bennett M., Caderni G., Clune Y., Hughes R., Karlsson P.C., Klinder A., ORiordan M., OSullivan G.C., Pool-Zobel P., et al. Toxicol Res (Camb). An Italian prospective cohort study showed that self-reported yogurt intake had an inverse association with colorectal cancer risk, but the authors evidenced that the above-mentioned factors can influence this result [48]. [69] compared samples of feces from healthy people and colorectal cancer patients. Lactic acid bacteria bacteriocins and probiotic preparations could provide an alternative for antibiotics [62]. Nielsen D.S., Cho G.S., Hanak A., Huch M., Franz C.M., Arneborg N. The effect of bacteriocin-producing. Mechanism of Actions of Food Preservation Procedures. Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. The intestinal microbiota has been linked to development of the gastrointestinal cancers also by production of toxic and genotoxic bacterial metabolites that can lead to mutations by binding specific cell surface receptors and affecting intracellular signal transduction [74]. In a study by Zackular et al. It is worthy to note that the immunomodulatory properties are strain dependent; the survival and the persistence into the gastrointestinal tract, as well as the posology, can also strongly influence the immune system. For future perspectives, the evaluation of the microbiome in the development of new markers and therapeutic agents in CC is highly recommended. Regulation of human epithelial tight junction proteins by, http://creativecommons.org/licenses/by/4.0/, Cell colony formation in cancer cells (N/E on normal colonocytes), Cell proliferation Induction of apoptosis, ACF -glucuronidase and -glucosidase activity. Findings show that Fusobacterium enrichment is associated with specific molecular subsets of colorectal cancers, offering support for a pathogenic role in colorectal cancer for a gut microbiome component [60,61]. These results show that probiotics have anti-cancer properties. The study also demonstrated the mechanisms for which it occurs: Repairing damages in the jejunal villi, and reducing mRNA expression of TNF-alpha, IL-1 beta, and IL-6 in intestinal tissue [55]. The appropriate balance between bacterial populations ensures homeostasis of the gastrointestinal tract. At least nine human mucin (MUC) genes have been identified, and MUC1, MUC2, MUC3, MUC4 and MUC5AC are expressed in the human colon. Butyric acid can contribute in the prevention of colorectal cancer because it is capable of improving the intestinal barrier through the increase in mucus production, and in the proliferation of healthy cells (Figure 2). Ciorba M.A., Riehl T.E., Rao M.S., Moon C., Ee X., Nava G.M., Walker M.R., Marinshaw J.M., Stappenbeck T.S., Stenson W.F. In recent years, reports have shown that dietary probiotics such as kefir have a great potential for cancer prevention and treatment. Undoubtedly, the gut microbiota can promote either health or tumor progression (in case of dysbiosis for instance) through its inflammatory and proliferative effects likely dependent on the context and genetic factors of the host as well. The probiotics formulation significantly decreased the risk of postoperative complications, namely mechanical ventilation, infections and anastomotic leakage. sterlund P., Ruotsalainen T., Korpela R., Saxelin M., Ollus A., Valta P., Kouri M., Elomaa I., Joensuu H. El-Nezami H.S., Polychronaki N.N., Ma J., Zhu H., Ling W., Salminen E.K., Juvonen R.O., Salminen S.J., Poussa T., Mykknen H.M. Probiotic supplementation reduces a biomarker for increased risk of liver cancer in young men from Southern China. October 3, 2017 Anticancer Properties of The Probiotic Kefir: A Review James Nam, PharmD Milk kefir Kefir, a probiotic mixture of kefir grains mixed with raw milk or water that has. Before Moreover, some strains of Bacillus and Saccharomyces are used [9]. Glutathione S-transferase (GST) is an antioxidant enzyme with detoxifying activity, which inactivates the carcinogens compounds such as reactive oxygen species (ROS) or xenobionts. It was also found that several species of the genus Salmonella and Clostridium were present in greater numbers in patients with colorectal cancer [70]. Symbols: activation; inhibition. All these activities, and especially the degradation of carcinogenetic enzymes, appear to be dependent on the strain and viability used as probiotics, as well as on the specific host condition (environmental intestinal conditions, such as pH, the presence of bile salts, and gastrointestinal enzymes). This is possible due to the rapid secretion of lactic acid from the cells, which causes the cytoplasmic pH in the cells to become more alkaline than the living environment. The aim of this review study was to evaluate the scientific evidence for effects of kefir on cancer prevention and treatment. The potential mechanisms involved in the anti-carcinogenic action of probiotics. Two potential probiotic lactobacillus strains isolated from olive microbiota exhibit adhesion and anti-proliferative effects in cancer cell lines. SCFAs are produced by intestinal microbiome in the fermentation of nondigestible carbohydrates (NDCs), undigested food fiber, or resistant starch (RS). Careers. The human gastrointestinal tract is a reservoir of a complex and dynamic population of microorganisms (the gut microbiota) mainly containing bacteria (in number over 1014), which exerts a significant influence on the host during homeostasis and disease [1]. Along with factors such as diet, lifestyle, genetics, and oncogenic infection, specific microorganisms or the variability of the microbiome, have been recently associated with this tumor. Gill H.S., Cross M.L. In a recent randomized control trial, colorectal cancer patients starting treatment with irinotecan were concurrently treated orally with a mixture of probiotic bacteria. Probiotics such as the lactic acid bacteria and Bifidobacterium as well as probiotic containing foods (kombucha, kefir, miso etc) have received lots of attention as anticancer agents for prevention and treatment. helped in preparing the figures. Wu S., Rhee K.J., Albesiano E., Wu X., Yen H.R., Huso D.L., Brancati F.L., Wick E., McAllister F., Housseau F., et al. The effects of perioperative probiotic treatment on serum zonulin concentration and subsequent postoperative infectious complications after colorectal cancer surgery: A double-center and doubleblind randomized clinical trial. In different studies, administration of probiotics such as Pediococcus pentosaceus or Lactobacillus plantarum in mice induced apoptosis and decreased the incidence of azoxymethane (AOM)-induced cancer [23,34]. 2,4-6 One study demonstrated that. Burns A.J., Rowland I.R. Inhibiting bacterial cooperation is an evolutionarily robust anti-biofilm strategy. In addition, scientists reports indicate the effectiveness of probiotic microorganisms (e.g., Bacillus: polyfermenticus, subtilis; Bifidobacterium: lactis, adolescentis; Clostridium butyricum; Enterococcus faecium; Lactobacillus: acidophilus, casei, fermentum, delbrueckii, helveticus, paracasei, pentosus, plantarum, salivarius, Lactococcus lactis; Pediococcus pentosaceus, Propionibacterium acidopropionici, Streptococcus thermophilus) in reducing proliferation and/or induction of apoptosis human colonic cancer cells such as Caco-2, HT-29, SW1116, HCT116, SW480, DLD-1, LoVo (Table 1). Studies have also demonstrated Bacteroides fragilis Clostridium and Escherichia coli to be over-presented in colon cancer patients [117]. Recent studies have identified overrepresentation of Fusobacterium in colorectal cancer tissues, but it is not yet clear whether this is pathogenic or simply an epiphenomenon. Implications for Nursing: Many patients use complementary and alternative medicine during cancer therapy. Natural sources which confer anti-carcinogenic effects for the prevention of colon cancer, such as probiotics, have been receiving important focus in recent years [36]. During this multifactorial carcinogenic process, a gradual alteration of microbiota, along with their microenvironment which causes dysbiosis and increases potential oncopathogenic microbes, can mediate the modulation of cancer (Figure 1). [39] the regular consumption of L. plantarum, L. acidophilus, and B. longum at a high dosage for 16 days, increased the diversity and microbial richness in individuals with CRC undergoing a colorectomy. These metabolites have genotoxic and cytotoxic activities, which can lead to abnormal cell growth and activation of anti-apoptotic pathways in the colonocytes, thereby contributing to the development of colorectal cancer [67]. A yogurt-like drink that is believed to have originated in the Caucasus Mountains of eastern Europe has become a popular product in natural health communities around the world. There are limited nutrients available at the distal part of the colon. -glucosidase, breaks down plant glycosides cycasin in the colon, generating aglycones, which are carcinogens [115]. The research results prove some strains of probiotics by modulating intestinal microbiota and immune response can be used for cancer prevention or/and as adjuvant treatment during anticancer chemotherapy. 2022 Aug 8;14(8):e27768. The evidence demonstrating the ability of the microbiota to modulate chemotherapy, radiotherapy, and immunotherapy with a particular focus on microbial composition, has started to become very impressive [50,51]. Bacteroides fragilis produces enterotoxigenic toxin (fragilysin), which affects the induction of inflammatory mediators, which leads to the progression of cancer [71]. Although promising results are coming from the studies on the interaction of microbiome-colon cancer, data evaluating probiotics as a potential means to affect cancer are still too scarce to formulate a definitive response. 8600 Rockville Pike Genetics of bacteriocins produced by lactic acid bacteria. Kostic A.D., Gevers D., Pedamallu C.S., Michaud M., Duke F., Earl A.M., Ojesina A.I., Jung J., Bass A.J., Tabernero J., et al. and transmitted securely. Contradictory results still exist in literature about the anticarcinogenic activities of probiotics. Lower intracolonic pH values (more acidic) inhibit the proliferation of pathogenic and putrefactive bacteria, as well as the activity of bacterial enzymes responsible for the production of carcinogenic compounds [137]. Beneficial activity of. K.. Koboziev I., Webb C.R., Furr K.L., Grisham M.B. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. MeSH Urbanska A.M., Paul A., Bhahena J., Prakash S. Suppression of tumorigenesis: Modulation of inflammatory cytokines by oral administration of microencapsulated probiotic yogurt formulation. Ewaschuk J.B., Walker J.W., Diaz H., Madsen K.L. I have attached links to a few medical publications so you can continue your research on the subject. Ghoneum and Felo [31] reported the effect of Lactobacillus kefiri, a novel kefir product, on the rate of apoptosis of gastric cancer cells, breast cancer cells, and human peripheral blood mononuclear cells (PBMCs). Infection during abdominal surgery, which is considered a factor in patients morbidity, can be reduced by administering probiotics to patients prior to surgery. In the first stages of biofilm formation, polysaccharides are secreted the most intensively and help first cells attach to the surface. This is usually a mixture of collagen, elastin and other proteins. Beneficial functions of probiotics lead to the restoration (in case of disturbance) and maintenance of intestinal homeostasis. Inclusion in an NLM database does not imply endorsement of, or agreement with, This research should pave the way in the future for the era of anticancer probiotics aimed at restoring gut eubiosis for a better clinical outcome in cancer patients. Both isomers are possessing effect against the spread of colon cancer cells [103]. Intestinal dysbiosis may be the reason for the tumorigenesis of both local gastro-intestinal cancers and tumors localized in distant sites of the body [6]. Koliarakis I., Psaroulaki A., Nikolouzakis T.K., Sgantzos M.N., Goulielmos G., Androutsopoulos V.P., Tsiaoussis J., Tsatsakis A., Kokkinakis M. Intestinal microbiota and colorectal cancer: A new aspect of research. Enhancement of epithelial barrier function by probiotics. Bacterial metabolites have also been seen to have a protective effect. In a study, it has been shown that kefir and ayran intake significantly decrease the DNA damage and the effect of ayran was dose dependent. Ohigashi S., Sudo K., Kobayashi D., Takahashi O., Takahashi T., Asahara T. Changes of the intestinal microbiota, short chain fatty acids, and fecal pH in patients with colorectal cancer. A deterioration of the intestinal environment was observed in the colorectal cancer patients in comparison to the healthy controls, and the intestinal environment improved when probiotics was taken, suggest the possibility of preventing colorectal carcinoma with probiotics. Their overabundance of sequences in tumors versus matched normal control tissue, and their positive association with lymph node metastasis has been observed [3,4,5]. Antigenotoxicity of probiotics and prebiotics on faecal water-induced DNA damage in human colon adenocarcinoma cells. Bookshelf Two bacterial phyla, gram-positive Firmicutes (Bacillus spp., Lactobacillus spp. Wada M., Nagata S., Saito M., Shimizu T., Yamashiro Y., Matsuki T., Asahara T., Nomoto K. Effects of the enteral administration of. Would you like email updates of new search results? Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. It has been seen in mice harboring an APC mutation in the intestinal epithelium, that adenoma formation is associated with the upregulation of cytokines, such as IL-6, IL-17, and IL-23 and the induction of proinflammatory Th17 cells [16]. Studies have shown, that Bifidobacterium longum, Lactobacillus acidophilus and Streptococcus salivarius strains could bind and cause the release in feces of heterocyclic amines and mutagens such as: 2-amino-3,4-dimethylimidazo [4,5-f] quinoline (MeIQ), 2-amino-3-methyl-3H-imidazo [4,5-f] quinoline (MHIQ), and 5-phenyl-2-amino-l-methylimidazo [4,5-f] pyridine (PhMIP), 3-amino-1-methyl 5 h pyrido[4,3-b] indole acetate (TrpP2) [124,125]. Thus, developing and applying techniques to ensure the viability of the probiotics strains, such as microencapsulation, could enhance the preventive effect of such strains on the CC development. Several species of probiotic bacteria, such as L. acidophilus, L. casei, L. plantarum, Propionibacterium freudenreichii, Lactobacillus delbrueckii, Bifidobacterium infantis, Bifidobacterium breve, Bifidobacterium longum, and Streptococcus thermophilus may also produce conjugated linoleic acids from linoleic acid. Ohara T., Yoshino K., Kitajima M. Possibility of preventing colorectal carcinogenesis with probiotics. Structural change in microbiota by a probiotic cocktail enhances the gut barrier and reduces cancer via TLR2 signaling in a rat model of colon cancer. thermofilus) on a daily basis for seven days. Duc N.M., Kim H.R., Chung K.Y. Klaenhammer T.R. shermanii JS on potentially arcinogenic bacterial activity in human colon. In the result, microorganisms become focused through polymerization or association. This may indicate that live bacteria produce metabolites or catalyze reactions that lead to amine detoxification. The results of many clinical studies indicate the effectiveness of probiotics in preventing, treating and reducing the progression of several types of cancer including colorectal, liver, breast, bladder, colon, and cervical in cancer patients (Table 4). 3. Ohara et al. Fusobacterium nucleatum and Porphyromonas gingivalis are identified as cancerogenic bacteria. A study by Kuugbee et al. Verma A., Shukla G. Probiotics Lactobacillus rhamnosus GG, Lactobacillus acidophilus suppresses DMH-induced procarcinogenic fecal enzymes and preneoplastic aberrant crypt foci in early colon carcinogenesis in Sprague Dawley rats. Cousin F.J., Jouan-Lanhouet S., Dimanche-Boitrel M.T., Corcos L., Jan G. Milk fermented by. Among compounds that inhibit the development of pathogenic microorganisms, organic acids are considered to be the most important, in particular lactic and acetic acid as well as hydrogen peroxide and bacteriocins [82]. rhamnosus, and Lactobacillus bulgaricus inhibited the growth of clinical isolates of Helicobacter pylori [138,139] and L. casei subsp. Federal government websites often end in .gov or .mil. Kefir was also found to induce apoptosis, as seen by cell death ELISA. Looking at this scenario, it could be strategically relevant to counteract the negative outcomes due to the presence of these microorganisms by using some selective bacteria with inhibitory effects against the pathobionts. Cureus. Potential mechanisms of action of lactic acid bacteria in pathways of apoptosis [50,107]. Some of probiotics are able to reduce intestinal permeability because they can modify components of the intestinal barrier, such as intracolonic pH, the production of mucins and the cellular junction proteins [136]. Salminen S., Bouley C., Boutron-Ruault M.-C., Cummings J.H., Franck A., Gibson G.R., Isolauri E., Moreau M.-C., Roberfroid M., Rowland I. Functional food science and gastrointestinal physiology and function. Weakness or fatigue. The risk of developing cancer depends on genetic factors, as well as the bodys immune status. This is the main reason why it will be necessary in the future to follow strict rules and have an efficient selection of bacteria to be included in the safe and effective probiotics list. Kefir has a remarkable ability to destroy cancer cells (all different types of cancers) without hurting normal cells. This to be associated with the occurrence of cationic exchange between the carcinogenic compounds and the peptidoglycan present in the cell walls of some probiotic microorganisms. A 6 oz serving of the beverage also contains 6 grams of protein, 20 percent of the daily recommended amount of calcium, as well as high amounts of phosphorous, vitamin B12, vitamin B2, and magnesium. Dietary interventions and food supplements, such as some selected probiotics, have emerged as a valid alternative to manage colon cancer. J. Physiol. Singh N., Gurav A., Sivaprakasam S., Brady E., Padia R., Shi H., Thangaraju M., Prasad P.D., Manicassamy S., Munn D.H., et al. Disclaimer. This paper aims to review the most recent articles in order to consider a possible adjuvant approach for the use of certain well-balanced probiotics to help prevent colon cancer and the adverse effects caused by related therapies. The increased incidence of apoptosis of cancer cells induced by probiotics has been attributed to SCFAs, particularly butyrate, which are able to induce epigenetic changes, paralyze the cell cycle, and stimulate the expression of proapoptotic genes. Kefir grains are a mixture of yeast and bacteria, living in a symbiotic association. Genetic identification, toxicity, gastrointestinal resistance, and colonization rate are the main requisites to design a good probiotic [8]. Bethesda, MD 20894, Web Policies The proapoptotic activity induced by the consumption of probiotics, especially by increasing TNF- production, is another factor well investigated in human cancer [44]. In a recent animal colorectal cancer (CRC) study [17], scientists illustrated the ways to replace missing metabolites in patients prone to gut inflammation and CRC, and how specific probiotics may become a new preventative or therapeutic strategy for patients at risk for inflammatory bowel disease (IBD)-associated CRC. A bacterial driverpassenger model for colorectal cancer: Beyond the usual suspects. The literature also shows that probiotics may have the ability to detoxify mycotoxins that may have carcinogenic properties [128,129]. Liver Physiol. induced selective genotoxic, cytotoxic, pro-apoptotic effects on leukemia and colon cancer cell lines, and as anti-inflammatory effects on macrophage cells at the molecular level. Cancers (Basel). Kefir is fermented milk with Caucasian and Tibet origin, made from the incubation of kefir grains with raw milk or water. Probiotics are able to increase the activity of this enzyme through the action of butyrate, which could change the status of histone acetylation, thus increasing the expression of GST [114]. The apoptosis signaling pathways can be activated by probiotic bacteria (e.g., lactic acid bacteria; LAB) through a mitochondria-dependent (intrinsic) and a death receptordependent, mitochondria-independent (extrinsic) pathway (Figure 3) [50]. PMID: 19887347 DOI: 10.1188/09.ONF.E335-E342 Abstract Purpose/objectives: To determine kefir's effect on the prevention of gastrointestinal complaints and quality of life (QOL) in patients being treated for colorectal cancer. Mego M., Chovanec J., Vochyanova-Andrezalova I., Konkolovsky P., Mikulova M., Reckova M., Miskovska V., Bysticky B., Beniak J., Medvecova L., et al. In a study by Liu et al. Influence of carcinogen binding by lactic acid-producing bacteria on tissue distribution and in vivo mutagenicity of dietary carcinogens. Roediger W.E. Future perspectives that allow a fuller description of gut biodiversity and accurately monitor changes in response to anticancer therapy, will help to determine the role of probiotics in cancer prevention and in alleviating the adverse effects occurring consequently. Of cancers ) without hurting normal cells ( all different types of ). Walker kefir and colon cancer, Diaz H., Madsen K.L probiotic bacteria intestinal homeostasis to. 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