Risk Assessment of Genetically Modified Lactic Acid Bacteria Using the Concept of Substantial Equivalence

Abstract

The use of food-grade microorganisms such as lactic acid bacteria (LAB) is one of the most promising methods for delivering health promoting compounds. Since it is not always possible to obtain strains that have the ability to produce specific compounds naturally or that produce them in sufficient quantities to obtain physiological responses, genetic modifications can be performed to improve their output. The objective of this study was to evaluate if previously studied genetically modified LAB (GM-LAB), with proven in vivo beneficial effects, are just as safe as the progenitor strain from which they were derived. Mice received an elevated concentration of different GM-LAB or the native parental strain from which they were derived during a prolonged period of time, and different health parameters were evaluated. Similar growth rates, hematological values, and other physiological parameters were obtained in the animals that received the GM-LAB compared to those that were fed with the native strain. These results demonstrate that the GM-LAB used in this study are just as safe as the native strains from which they were derived and thus merit further studies to include them into the food chain.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. 1.

    Brouwer IA, van Dusseldorp M, West CE et al (1999) Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial. J Nutr 129:1135–1139

    CAS  PubMed  Google Scholar 

  2. 2.

    Hugenholtz J, Smid EJ (2002) Nutraceutical production with food-grade microorganisms. Curr Opin Biotechnol 13:497–507

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Sybesma W, Hugenholtz J, de Vos WM et al (2006) Safe use of genetically modified lactic acid bacteria in food. Bridging the gap between consumers, green groups, and industry. Elect J Biotechnol 9:424–448

    Google Scholar 

  4. 4.

    LeBlanc JG, Sybesma W, Starrenburg M et al (2010) Supplementation with engineered Lactococcus lactis improves the folate status in deficient rats. Nutrition 26

  5. 5.

    LeBlanc JG, Burgess C, Sesma F et al (2005) Ingestion of milk fermented by genetically modified Lactococcus lactis improves the riboflavin status of deficient rats. J Dairy Sci 88:3435–3442

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    LeBlanc JG, Ledue-Clier F, Bensaada M et al (2008) Ability of Lactobacillus fermentum to overcome host alpha-galactosidase deficiency, as evidenced by reduction of hydrogen excretion in rats consuming soya alpha-galacto-oligosaccharides. BMC Microbiol 8:22

    Article  PubMed  Google Scholar 

  7. 7.

    LeBlanc JG, Piard JC, Sesma F et al (2005) Lactobacillus fermentum CRL 722 is able to deliver active alpha-galactosidase activity in the small intestine of rats. FEMS Microbiol Lett 248:177–182

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Kuipers OP, de Ruyter PG, Kleerebezem M et al (1998) Quorum sensing-controlled gene expression in lactic acid bacteria. J Biotechnol 177:66–74

    Google Scholar 

  9. 9.

    LeBlanc JG, Garro MS, Savoy de Giori G et al (2004) A Novel Functional Soy-based Food Fermented by Lactic Acid Bacteria: Effect of Heat Treatment. J Food Sci 69:M246–M250

    CAS  Google Scholar 

  10. 10.

    Sainte-Marie G (1962) A paraffin embedding technique for studies employing immunofluorescence. J Histochem Cytochem 10:150–156

    Google Scholar 

  11. 11.

    Wegmann U, O’Connell-Motherway M, Zomer A et al (2007) Complete genome sequence of the prototype lactic acid bacterium Lactococcus lactis subsp. cremoris MG1363. J Bacteriol 189:3256–3270

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Mierau I, Kleerebezem M (2005) 10 years of the nisin-controlled gene expression system (NICE) in Lactococcus lactis. Appl Microbiol Biotechnol 68:705–717

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Nouaille S, Ribeiro LA, Miyoshi A et al (2003) Heterologous protein production and delivery systems for Lactococcus lactis. Genet Mol Res 2:102–111

    PubMed  Google Scholar 

  14. 14.

    Gasson MJ (1983) Plasmid complements of Streptococcus lactis NCDO 712 and other lactic streptococci after protoplast-induced curing. J Bacteriol 154:1–9

    CAS  PubMed  Google Scholar 

  15. 15.

    Sybesma W, Van Den Born E, Starrenburg M et al (2003) Controlled modulation of folate polyglutamyl tail length by metabolic engineering of Lactococcus lactis. Appl Environ Microbiol 69:7101–7107

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Burgess C, O’Connell-Motherway M, Sybesma W et al (2004) Riboflavin production in Lactococcus lactis: potential for in situ production of vitamin-enriched foods. Appl Environ Microbiol 70:5769–5777

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    LeBlanc JG, Silvestroni A, Connes C et al (2004) Reduction of non-digestible oligosaccharides in soymilk: application of engineered lactic acid bacteria that produce alpha-galactosidase. Genet Mol Res 3:432–440

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), the Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT), Consejo de Investigaciones de la Universidad Nacional de Tucumán (CIUNT) ECOS-Sud (Paris, France) and the European Commission through contract QLK1-CT-2000-01376 (Nutracells).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jean Guy LeBlanc.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

LeBlanc, J.G., Van Sinderen, D., Hugenholtz, J. et al. Risk Assessment of Genetically Modified Lactic Acid Bacteria Using the Concept of Substantial Equivalence. Curr Microbiol 61, 590–595 (2010). https://doi.org/10.1007/s00284-010-9657-7

Download citation

Keywords

  • Lactis
  • Lactic Acid Bacterium
  • Genetically Modify Organism
  • Native Strain
  • Megaloblastic Anemia