Proteobiotics

Proteobiotics are natural metabolites which are produced by fermentation process of specific probiotic strains.[1][2] These small oligopeptides[3] were originally discovered in and isolated from culture media used to grow probiotic bacteria and may account for some of the health benefits of probiotics.

Several genera of probiotic bacteria are known to produce proteobiotics, including Lactococcus spp.,[3] Pediococcus spp.[3] Lactobacillus spp.[4] and Bifidobacterium spp.[5]

Mode of action

Recent studies have explored mode of action of proteobiotics and their potential benefits in maintaining the ratio of beneficial bacteria, lowering bacterial imbalance, and improving gut function. However, any of the statements based on research have not been evaluated by the US Food and Drug Administration.

Unlike other molecules produced by probiotic bacteria, such as organic acids and bacteriocins, proteobiotics are natural metabolites which interfere with quorum sensing, the cell-to-cell communications which occur between bacterial cells, mainly by interfering with the LuxS quorum sensing system.[5][4][1] These quorum-sensing systems allow bacteria to respond to changes in their environment and play a role in the ability of pathogens to evade host defence mechanisms. By interfering with quorum sensing, proteobiotics inhibit the cascade of events leading to adhesion to, and invasion of, host cells. This is achieved through reduced expression of specific virulence genes (typically found on pathogenicity islands) that facilitate the infection process. Specifically, proteobiotics inhibit virulence genes involved in toxin production,[4][1] biofilm formation,[6] cell adhesion[5][7] and invasion.[8][3] In enterohemorrhagic E. coli and Salmonella spp., genes associated with Type 3 Secretion Systems seem to be the main targets.[9]

The degree to which proteobiotics can reduce virulence-gene expression depends on the pathogen and the source of the proteobiotics. Lactobacillus acidophilus-derived proteobiotics down-regulate virulence genes in enterohemorrhagic Escherichia coli,[4] Clostridium difficile[1], Salmonella Typhimurium[3], Listeria monocytogenes[10] and Campylobacter jejuni[8]. Whereas those produced by Bifidobacterium spp. have been shown to impact virulence gene expression in Campylobacter jejuni,[8] enterohemorrhagic Escherichia coli,[4] Clostridium difficile,[1] Clostridium perfringens,[7] and Salmonella Typhimurium[9].

References

  1. 1 2 3 4 5 Yun, B.; Oh, S.; Griffiths, M.W. (2014). "Lactobacillus acidophilus modulates the virulence of Clostridium difficile". Journal of Dairy Science. 97 (8): 4745–4758. doi:10.3168/jds.2014-7921. PMID 24856984.
  2. ↑ ZEINHOM, MOHAMED; TELLEZ, ANGELA M.; DELCENSERIE, VERONIQUE; EL-KHOLY, A. M.; EL-SHINAWY, S. H.; GRIFFITHS, MANSEL W. (2016-11-30). "Yogurt Containing Bioactive Molecules Produced by Lactobacillus acidophilus La-5 Exerts a Protective Effect against Enterohemorrhagic Escherichia coli in Mice". Journal of Food Protection. 75 (10): 1796–1805. doi:10.4315/0362-028x.jfp-11-508. PMID 23043828.
  3. 1 2 3 4 5 Tessema, Akalate. “Lactic Acid Bacteria and Culture Media for the Production of Potential Antivirulence Peptides against Salmonella Typhimurium.” M.Sc. Thesis. University of Guelph, 2015.
  4. 1 2 3 4 5 Medellin-Peña, Maira Jessica; Wang, Haifeng; Johnson, Roger; Anand, Sanjeev; Griffiths, Mansel W. (2007-07-01). "Probiotics Affect Virulence-Related Gene Expression in Escherichia coli O157:H7". Applied and Environmental Microbiology. 73 (13): 4259–4267. doi:10.1128/AEM.00159-07. ISSN 0099-2240. PMC 1932779. PMID 17496132.
  5. 1 2 3 Medellin-Peña, Maira J.; Griffiths, Mansel W. (2009-02-15). "Effect of Molecules Secreted by Lactobacillus acidophilus Strain La-5 on Escherichia coli O157:H7 Colonization". Applied and Environmental Microbiology. 75 (4): 1165–1172. doi:10.1128/AEM.01651-08. ISSN 0099-2240. PMC 2643578. PMID 19088323.
  6. ↑ Kim, Younghoon; Lee, Jae Won; Kang, Seo-Gu; Oh, Sejong; Griffiths, Mansel W. (2012-10-01). "Bifidobacterium spp. influences the production of autoinducer-2 and biofilm formation by Escherichia coli O157:H7". Anaerobe. 18 (5): 539–545. doi:10.1016/j.anaerobe.2012.08.006. ISSN 1095-8274. PMID 23010308.
  7. 1 2 Troll, Marie-Luise. “Investigating the Anti-Virulent Activity of Probiotic Bioactives on Clostridium Perfringens.” M.Sc. Thesis. Universitat Autònoma de Barcelona, 2014.
  8. 1 2 3 MUNDI, A.; DELCENSERIE, V.; AMIRI-JAMI, M.; MOORHEAD, S.; GRIFFITHS, M. W. (2016-11-30). "Cell-Free Preparations of Lactobacillus acidophilus Strain La-5 and Bifidobacterium longum Strain NCC2705 Affect Virulence Gene Expression in Campylobacter jejuni". Journal of Food Protection. 76 (10): 1740–1746. doi:10.4315/0362-028x.jfp-13-084. PMID 24112574.
  9. 1 2 Bayoumi, Mohamed A.; Griffiths, Mansel W. (2012-06-01). "In vitro inhibition of expression of virulence genes responsible for colonization and systemic spread of enteric pathogens using Bifidobacterium bifidum secreted molecules". International Journal of Food Microbiology. 156 (3): 255–263. doi:10.1016/j.ijfoodmicro.2012.03.034. ISSN 1879-3460. PMID 22541391.
  10. ↑ Delcenserie, V.; Griffiths, M.W. "Mitigation of the Effects of Listeria monocytogenes using probiotics." Presentation at OMAF 2013 Food Safety Research Forum, May 9, 2013, Guelph, ON.
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