Probiotical Cell Fragments (PCFs) as “Novel Nutraceutical Ingredients”

Nditange Shigwedha, Liubov Sichel, Li Jia, Lanwei Zhang

1School of Food Science and Engineering, Harbin Institute of Technology, Harbin, PR China 2Department of Food Science and Technology, University of Namibia, Windhoek, Namibia 3Pure Research Products LLC, Boulder, USA 4Wyeth Nutrition, Suzhou, China.

DOI: 10.4236/jbm.2014.23007                

Abstract

Probiotical cell fragments (PCFs) are structural components of the probiotic cell lysate(s) and exhibit similar beneficial effects on the host as live probiotic bacteria. With cell fragment technology (CFT?), the structural fragments are isolated and purified from live probiotic cells. While observed to be strain-dependent as in the case of live probiotics, orally administered PCFs demonstrated a broad spectrum of immune modulation functions; anti-allergy; anti-inflammation; anti-bacterial and anti-viral properties; anti-mutagenic; and radioprotective and detoxification abilities in humans and animals. The PCFs mechanisms of action include events of motifs of cell wall peptidoglycans, DNA motifs, nucleotide containing components, lipoteichoic acids (LPAs), surface layer (S-layer) proteins, and cytoplasmic proteins. Different immunological in vivo-in vitro tests have shown that PCFs, essentially, have the ability to stimulate the macrophages, and induce cytokines such as interleukins, tumor necrosis factors (TNFs), interferons (IFNs), and natural killer (NK) cells. PCFs may be used as ingredients for foods and beverages or as nutritional supplements with long term stability and shelf-life up to 5 years. PCFs may also be used as health restorative ingredients in cosmetic products. The outcome of probiotics CFT? stands as an advantage to the food and pharmaceutical industries, regarding the formulation of novel products with unadulterated sensory characteristics of origin. Hence, PCFs are being characterized here as “novel nutraceutical ingredients” for health maintenance in both humans and animals.

Keywords

Probiotical Cell Fragments (PCFs), Paraprobiotics, Immunobiotics, Immunomodulator, Nutraceutical Ingredients, Lactic Acid Bacteria (LAB)

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	FAO/WHO (2002) Guidelines for the Evaluation of Probiotics in Food. http://www.who.int/entity/foodsafety/publications/fs_management/probiotics2/en
[2]	Taverniti, V. and Guglielmetti, S. (2011) The Immunomodulatory Properties of Probiotic Microorganisms beyond their Viability (Ghost Probiotics: Proposal of Paraprobiotic Concept). Genes and Nutrition, 6, 261-274. http://dx.doi.org/10.1007/s12263-011-0218-x [Google Scholar] [CrossRef] [PubMed]
[3]	Saito, T. and Kitazawa, H. (2005) Recent Tendency of Immunogenics Research on Lactic Acid Bacteria. Bulletin of Japan Dairy Technical Association, 55, 34-44. (In Japanese)
[4]	Kitazawa, H., Tohno, M. Shimosato, T. and Saito, T. (2008) Development of Molecular Immunoassay System for Probiotics via Toll-Like Receptors Based on Food Immunology. Animal Science Journal, 79, 11-21. http://dx.doi.org/10.1111/j.1740-0929.2007.00491.x-i1 [Google Scholar] [CrossRef]
[5]	Kitazawa, H., Villena, J. and Alvarez, S. (2013) Probiotics: Immunobiotics and Immunogenics. CRC Press, Boca Raton.
[6]	Lebeer, S., Vanderleyden, J. and De Keersmaecker, C.J. (2010) Host Interactions of Probiotic Bacterial Surface Molecules: Comparison with Commensals and Pathogens. Nature Reviews Microbiology, 8, 171-184. http://dx.doi.org/10.1038/nrmicro2297 [Google Scholar] [CrossRef] [PubMed]
[7]	Kleerebezem, M., Hols, P., Bernard, E., Rolain, T., Zhou, M., Siezen, R.J. and Bron, P.A. (2010) The Extracellular Biology of the Lactobacilli. FEMS Microbiology Reviews, 34, 199-230. http://dx.doi.org/10.1111/j.1574-6976.2009.00208.x [Google Scholar] [CrossRef] [PubMed]
[8]	Kaji, R., Kiyoshima-Shibata, J., Nagaoka, M., Nanno, M. and Shida, K. (2010) Bacterial Teichoic Acids Reverse Predominant IL-12 Production Induced by Certain Lactobacillus Strains into Predominant IL-10 Production via TLR2-Dependent ERK Activation in Macrophages. The Journal of Immunology, 184, 3505-3513. http://dx.doi.org/10.4049/jimmunol.0901569 [Google Scholar] [CrossRef] [PubMed]
[9]	Clancy, R. (2003) Immunobiotics and the Probiotic Evolution. FEMS Immunology and Medical Microbiology, 38, 9-12. http://dx.doi.org/10.1016/S0928-8244(03)00147-0 [Google Scholar] [CrossRef]
[10]	Underhill, D.M. and Ozinsky, A. (2002) Toll-Like Receptors: Key Mediators of Microbe Detection. Current Opinion in Immunology, 14, 103-110. http://dx.doi.org/10.1016/S0952-7915(01)00304-1 [Google Scholar] [CrossRef]
[11]	Lebeer, S., Vanderleyden, J. and De Keersmaecker, S.C. (2008) Genes and Molecules of Lactobacilli Supporting Probiotic Action. Microbiology and Molecular Biology Reviews, 72, 728-764. http://dx.doi.org/10.1128/MMBR.00017-08 [Google Scholar] [CrossRef]
[12]	Hornung, V., Ablasser, A., Charrel-Dennis, M., et al. (2009) AIM2 Recognizes Cytosolic dsDNA and Forms a Caspase-1-Activating Inflammasome with ASC. Nature, 458, 514-518. http://dx.doi.org/10.1038/nature07725 [Google Scholar] [CrossRef] [PubMed]
[13]	Ouwehand, A.C. (2007) Antiallergic Effects of Probiotics. The Journal of Nutrition, 137, 794S-797S.
[14]	Hemmi, H., Takeuchi, O., Kawai, T., et al. (2000) A Toll-Like Receptor Recognizes Bacterial DNA. Nature, 408, 740- 745. http://dx.doi.org/10.1038/35047123 [Google Scholar] [CrossRef] [PubMed]
[15]	Kawai, T. and Akira, S. (2011) Toll-Like Receptors and their Crosstalk with other Innate Receptors in Infection and Immunity. Immunity, 34, 637-650. http://dx.doi.org/10.1016/j.immuni.2011.05.006 [Google Scholar] [CrossRef] [PubMed]
[16]	Beutler, B.A. (2009) TLRs and Innate Immunity. Blood, 113, 1399-1407. http://dx.doi.org/10.1182/blood-2008-07-019307 [Google Scholar] [CrossRef] [PubMed]
[17]	Rhee, S.H. (2011) Basic and Translational Understandings of Microbial Recognition by Toll-Like Receptors in the Intestine. Journal of Neurogastroenterology and Motility, 17, 28-34. http://dx.doi.org/10.5056/jnm.2011.17.1.28 [Google Scholar] [CrossRef] [PubMed]
[18]	Del-Immune, V. (2014) Del-Immune V®. http://www.delimmune.com/research
[19]	Tohno, M. and Kitazawa, H. (2013) Molecular Immunoassay Systems for Probiotics via Pattern Recognition Receptors. In: Kitazawa, H., Villena, J. and Alvarez, S., Eds., Probiotics: Immunobiotics and Immunogenics, CRC Press, Boca Raton, 54-88. http://dx.doi.org/10.1201/b15532-5 [Google Scholar] [CrossRef]
[20]	Humen, M.A., Benyacoub, J., Minnaard, J., et al. (2013) Immunobiotics and Immunity against Parasites. In: Kitazawa, H., Villena, J. and Alvarez, S., Eds., Probiotics: Immunobiotics and Immunogenics, CRC Press, Boca Raton, 194-214. http://dx.doi.org/10.1201/b15532-9 [Google Scholar] [CrossRef]
[21]	Stadelmann, B., Merino, M.C., Persson, L. and Sv?rd, S.G. (2012) Arginine Consumption by the Intestinal Parasite Giardia Intestinalis Reduces Proliferation of Intestinal Epithelial Cells. PloS One, 7, e45325. http://dx.doi.org/10.1371/journal.pone.0045325 [Google Scholar] [CrossRef]
[22]	Cerutti, A. and Rescigno, M. (2008) The Biology of Intestinal Immunoglobulin A Responses. Immunity, 28, 740-750. http://dx.doi.org/10.1016/j.immuni.2008.05.001 [Google Scholar] [CrossRef] [PubMed]
[23]	Makino, S., Ikegami, S., Nagai, T. and Yamada, H. (2013) Immunogenics: Extracellular Polysaccharides Reduce the Risk of Infection. In: Kitazawa, H., Villena, J. and Alvarez, S., Eds., Probiotics: Immunobiotics and Immunogenics, CRC Press, Boca Raton, 376-397. http://dx.doi.org/10.1201/b15532-16 [Google Scholar] [CrossRef]
[24]	Yoda, K., Miyazawa, K., Harata, G. and He, F. (2013) Immunobiotics and Antiviral Immunity. In: Kitazawa, H., Villena, J. and Alvarez, S., Eds., Probiotics: Immunobiotics and Immunogenics, CRC Press, Boca Raton, 169-193. http://dx.doi.org/10.1201/b15532-8 [Google Scholar] [CrossRef]
[25]	Christensen, H.R. and Frøkiær, H. (2007) Immunomodulating Effects of Lactic Acid Bacteria. In: Shetty, K., Paliyath, G., Pometto, A.L. and Levin, R.E., Eds., Functional Foods and Biotechnology, CRC Press, New York, 435-471.
[26]	Matsumoto, M., Tani, H., Ono, H., Ohishi, H. and Benno, Y. (2002) Adhesive Property of Bifidobacterium Lactis LKM512 and Predominant Bacteria of Intestinal Microflora to Human Intestinal Mucin. Current Microbiology, 44, 212-215. http://dx.doi.org/10.1007/s00284-001-0087-4 [Google Scholar] [CrossRef] [PubMed]
[27]	Chen, X.Y., Xu, J.J., Shuai, J.B., Chen, J.S., Zhang, Z.F. and Fang, W.H. (2007) The S-Layer Proteins of Lactobacillus Crispatus Strain ZJ001 Is Responsible for Competitive Exclusion against Escherichia coli O157:H7 and Salmonella Typhimurium. International Journal of Food Microbiology, 115, 307-312. http://dx.doi.org/10.1016/j.ijfoodmicro.2006.11.007 [Google Scholar] [CrossRef] [PubMed]
[28]	Xue, C., Zhang, L., Li, H., et al. (2013) Functionality of the S-Layer Proteins from Lactobacillus in the Competitive against Enteropathogens Infection. European Food Research and Technology, 236, 249-255. http://dx.doi.org/10.1007/s00217-012-1871-z [Google Scholar] [CrossRef]
[29]	Lee, Y.K., Puong, K.Y., Ouwehand, A.C. and Salminen, S. (2003) Displacement of Bacterial Pathogens from Mucus and Caco-2 Cell Surface by Lactobacilli. Journal of Medical Microbiology, 52, 925-930. http://dx.doi.org/10.1099/jmm.0.05009-0 [Google Scholar] [CrossRef] [PubMed]
[30]	Klein, G., Schanstra, J.P., Hoffmann, J., Mischak, H., Siwy, J. and Zimmermann, K. (2013) Proteomics as a Quality Control Tool of Pharmaceutical Probiotic Bacterial Lysate Products. PloS One, 8, e66682. http://dx.doi.org/10.1371/journal.pone.0066682 [Google Scholar] [CrossRef] [PubMed]
[31]	Bowdish, D.M., Davidson, D.J., Scott, M.G. and Hancock, R.E. (2005) Immunomodulatory Activities of Small Host Defense Peptides. Antimicrobial Agents and Chemotherapy, 49, 1727-1732. http://dx.doi.org/10.1128/AAC.49.5.1727-1732.2005 [Google Scholar] [CrossRef]
[32]	Afacan, N.J., Janot, L.M. and Hancock, R.E.W. (2013) Host Defense Peptides: Immune Modulation and Antimicrobial Activity in Vivo. In: Hiemstra, P.S. and Zaat, S.A.J., Eds., Antimicrobial Peptides and Innate Immunity, Springer, Basel, 321-358.
[33]	Valdez, J.C., Ramos, A.N., Fernández, D., et al. (2013) Probiotics and their Potential Use in Wound Treatment. In: Kitazawa, H., Villena, J. and Alvarez, S., Eds., Probiotics: Immunobiotics and Immunogenics, CRC Press, Boca Raton, 298-335. http://dx.doi.org/10.1201/b15532-13 [Google Scholar] [CrossRef]
[34]	Liu, W., Zhang, L., Yi, H., et al. (2014) Qualitative Detection of Class IIa Bacteriocinogenic Lactic Acid Bacteria from Traditional Chinese Fermented Food Using a YGNGV-Motif-Based Assay. Journal of Microbiological Methods, 100, 121-127. http://dx.doi.org/10.1016/j.mimet.2014.03.006 [Google Scholar] [CrossRef] [PubMed]
[35]	Shimosato, T. and Kitazawa, H. (2013) Immunogenics: Immunostimulatory Oligodeoxynucleotides from Probiotics. In: Kitazawa, H., Villena, J. and Alvarez, S., Eds., Probiotics: Immunobiotics and Immunogenics, CRC Press, Boca Raton, 336-350. http://dx.doi.org/10.1201/b15532-14 [Google Scholar] [CrossRef]
[36]	Ramaprakash, H., Shibata, T., Duffy, K.E., et al. (2011) Targeting ST2L Potentiates CpG-Mediated Therapeutic Effects in a Chronic Fungal Asthma Model. The American Journal of Pathology, 179, 104-115. http://dx.doi.org/10.1016/j.ajpath.2011.03.032 [Google Scholar] [CrossRef] [PubMed]
[37]	Jolly, L., Vincent, S.J.F., Duboc, P. and Neeser, J.R. (2002) Exploiting Exopolysaccharides from Lactic Acid Bacteria. Antonie van Leeuwenhoek, 82, 367-374. http://dx.doi.org/10.1023/A:1020668523541 [Google Scholar] [CrossRef]
[38]	Nakajima, H., Suzuki, Y. and Hirota, T. (1992) Cholesterol Lowering Activity of Ropy Fermented Milk. Journal of Food Science, 57, 1327-1329. http://dx.doi.org/10.1111/j.1365-2621.1992.tb06848.x [Google Scholar] [CrossRef]
[39]	Galdeano, C.M., Dogi, A.C. and Perdigón, G. (2013) Difference in the Signals Induced by Commensal or Probiotic Bacteria to the Gut Epithelial and Immune Cells. In: Kitazawa, H., Villena, J. and Alvarez, S., Eds., Probiotics: Immunobiotics and Immunogenics, CRC Press, Boca Raton, 36-53. http://dx.doi.org/10.1201/b15532-4 [Google Scholar] [CrossRef]
[40]	Wang, S., Zhang, L., Fan, R., et al. (2014) Induction of HT-29 Cells Apoptosis by Lactobacilli Isolated from Fermented Products. Research in Microbiology, 165, 202-214. http://dx.doi.org/10.1016/j.resmic.2014.02.004 [Google Scholar] [CrossRef] [PubMed]
[41]	Tokunaga, T., Yamamoto, H., Shimada, S., et al. (1984) Antitumor Activity of Deoxyribonucleic Acid Fraction from Mycobacterium Bovis BCG. I. Isolation, Physicochemical Characterization, and Antitumor Activity. Journal of the National Cancer Institute, 72, 955-962.
[42]	Klinman, D.M. (2004) Immunotherapeutic uses of CpG oligodeoxynucleotides. Nature Reviews Immunology, 4, 249- 259. http://dx.doi.org/10.1038/nri1329 [Google Scholar] [CrossRef] [PubMed]
[43]	Yanai, H., Chiba, S., Ban, T., et al. (2011) Suppression of Immune Responses by Nonimmunogenic Oligodeoxynucleotides with High Affinity for High-Mobility Group Box Proteins (HMGBs). Proceedings of the National Academy of Sciences, 108, 11542-11547. http://dx.doi.org/10.1073/pnas.1108535108 [Google Scholar] [CrossRef] [PubMed]
[44]	Nicholls, D.G. and Ward, M.W. (2000) Mitochondrial Membrane Potential and Neuronal Glutamate Excitotoxicity: Mortality and Millivolts. Trends in Neurosciences, 23, 166-174. http://dx.doi.org/10.1016/S0166-2236(99)01534-9 [Google Scholar] [CrossRef]