Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Assessing the survival of transgenic plant DNA in the human gastrointestinal tract

Abstract

The inclusion of genetically modified (GM) plants in the human diet has raised concerns about the possible transfer of transgenes from GM plants to intestinal microflora and enterocytes. The persistence in the human gut of DNA from dietary GM plants is unknown. Here we study the survival of the transgene epsps from GM soya in the small intestine of human ileostomists (i.e., individuals in which the terminal ileum is resected and digesta are diverted from the body via a stoma to a colostomy bag). The amount of transgene that survived passage through the small bowel varied among individuals, with a maximum of 3.7% recovered at the stoma of one individual. The transgene did not survive passage through the intact gastrointestinal tract of human subjects fed GM soya. Three of seven ileostomists showed evidence of low-frequency gene transfer from GM soya to the microflora of the small bowel before their involvement in these experiments. As this low level of epsps in the intestinal microflora did not increase after consumption of the meal containing GM soya, we conclude that gene transfer did not occur during the feeding experiment.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: PCR amplification of epsps derived from the intestinal tract of ileostomists.
Figure 2: Recovery of the epsps transgene and the indigestible marker PEG 4000.
Figure 3: Relationship between recovery of the epsps transgene and the soya lectin gene Le1.
Figure 4: Influence of PEG4000 on DNAase activity.

References

  1. Gebhard, F. & Smalla, K. Transformation of Acinetobacter sp. strain BD413 by transgenic sugar beet DNA. Appl. Environ. Microbiol. 64, 1550–1554 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Einspanier, R. et al. The fate of forage plant DNA in farm animals: a collaborative case-study investigating cattle and chicken fed recombinant plant material. Eur. Food Res. Technol. 212, 129–134 (2001).

    Article  CAS  Google Scholar 

  3. Schubbert, R., Lettmann, C. & Doerfler, W. Ingested foreign (phage M13) DNA survives transiently in the gastrointestinal tract and enters the bloodstream of mice. Mol. Gen. Genet. 242, 495–504 (1994).

    Article  CAS  PubMed  Google Scholar 

  4. Schubbert, R., Renz, D., Schmitz, B. & Doerfler, W. Foreign (M13) DNA ingested by mice reaches peripheral leukocytes, spleen, and liver via the intestinal wall mucosa and can be covalently linked to mouse DNA. Proc. Natl. Acad. Sci. USA 94, 961–966 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Schubbert, R., Hohlweg, U., Renz, D. & Doerfler, W. On the fate of orally ingested foreign DNA in mice: chromosomal association and placental transmission to the fetus. Mol. Gen. Genet. 259, 569–576 (1998).

    Article  CAS  PubMed  Google Scholar 

  6. Mercer, D.K., Scott, K.P., Bruce-Johnson, W.A., Glover, L.A. & Flint, H.J. Fate of free DNA and transformation of the oral bacterium Streptococcus gordonii DL1 by plasmid DNA in human saliva. Appl. Environ. Microbiol. 65, 6–10 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Duggan, P.S., Chambers, P.A., Heritage, J. & Forbes, J.M. Survival of free DNA encoding antibiotic resistance from transgenic maize and the transformation activity of DNA in ovine saliva, ovine rumen fluid and silage effluent. FEMS Microbiol. Letts. 191, 71–77 (2000).

    Article  CAS  Google Scholar 

  8. Netherwood, T. et al. Gene transfer in the gastrointestinal tract. Appl. Environ. Microbiol. 65, 5139–5141 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Chambers, P.A., Duggan, P.S., Heritage, J. & Forbes, J.M. The fate of antibiotic resistance marker genes in transgenic plant feed material fed to chickens. J. Antimicrob. Chemother. 49, 161–164 (2002).

    Article  CAS  PubMed  Google Scholar 

  10. Martín-Orúe, S.M. et al. Degradation of transgenic DNA from genetically modified soya and maize in human intestinal simulations. Br. J. Nutr. 87, 533–542 (2002).

    Article  PubMed  Google Scholar 

  11. Vodkin, L.O., Rhodes, P.R. & Goldberg, R.B. cA lectin gene insertion has the structural features of a transposable element. Cell 34, 1023–1031 (1983).

    Article  CAS  PubMed  Google Scholar 

  12. Meyer, R., Chardonnens, F., Hubner, P. & Luthy, J. Polymerase chain reaction (PCR) in the quality and safety assurance of food: detection of soya in processed meat products. Z. Lebensm. Unters. Forsch. 203, 339–344 (1996).

    Article  CAS  PubMed  Google Scholar 

  13. Studer, E., Rhyner, C., Lüthy, J. & Hübner, P. Quantitative competitive PCR for the detection of genetically modified soybean and maize. Z. Lebensm. Unters. Forsch. 207, 207–213 (1998).

    Article  CAS  Google Scholar 

  14. Adlerberth, I. et al. A mannose-specific adherence mechanism in Lactobacillus plantarum conferring binding to the human colonic cell line HT-29. Appl. Environ. Microbiol. 62, 2244–2251 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Hoiseth, S.K. & Stocker, B.A.D. Aromatic dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature 291, 238–239 (1981).

    Article  CAS  PubMed  Google Scholar 

  16. Hidalgo, I.J., Raub, T.J. & Borchardt, R.T. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 96, 736–749 (1989).

    Article  CAS  PubMed  Google Scholar 

  17. Andersson, H. The ileostomy model for the study of carbohydrate digestion and carbohydrate effects on sterol excretion in man. Eur. J. Clin. Nutr. 46, S69–76 (1992).

    PubMed  Google Scholar 

  18. Langkilde, A.M., Champ, M. & Andersson, H. Effects of high-resistant-starch banana flour (RS(2)) on in vitro fermentation and the small-bowel excretion of energy, nutrients, and sterols: an ileostomy study. Am. J. Clin. Nutr. 75, 104–111 (2002).

    Article  CAS  PubMed  Google Scholar 

  19. Normen, L., Laerke, H.N., Jensen, B.B., Langkilde, A.M. & Andersson, H. Small-bowel absorption of D-tagatose and related effects on carbohydrate digestibility: an ileostomy study. Am. J. Clin. Nutr. 73, 105–110 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Ruiz, T.R., Andrews, S. & Smith, G.B. Identification and characterization of nuclease activities in anaerobic environmental samples. Can. J. Microbiol. 46, 736–740 (2000).

    Article  CAS  PubMed  Google Scholar 

  21. McCartney, A.L. Application of molecular biological methods for studying probiotics and the gut flora. Br. J. Nutr. 88, S29–37 (2002).

    Article  CAS  PubMed  Google Scholar 

  22. Stach, J.E. & Burns, R.G. Enrichment versus biofilm culture: a functional and phylogenetic comparison of polycyclic aromatic hydrocarbon-degrading microbial communities. Environ. Microbiol. 4, 169–182 (2002).

    Article  PubMed  Google Scholar 

  23. Caldwell, D.E., Wolfaardt, G.M., Korber, D.R. & Lawrence, J.R. in Manual of Environmental Microbiology (eds. Hurst, J.H., Knudsen, G.R., McInerney, L.D., Stetzenbach, M.J. & Walter, W.V.) 79–90 (American Society for Microbiology Press, Washington, DC, 1997).

    Google Scholar 

  24. Yamo, T. et al. Abnormal expression of CD44 variants on the exfoliated cells in the faeces of patients with colorectal cancer. Gastroenterology 114, 1196–1205 (1998).

    Article  Google Scholar 

  25. Kerovuo, J. & Tynkkynen, S. Expression of Bacillus subtilis phytase in Lactobacillus plantarum 755. Lett. Appl. Microbiol. 30, 325–329 (2000).

    Article  CAS  PubMed  Google Scholar 

  26. Soole, K.L. et al. Constitutive secretion of a bacterial enzyme by polarized epithelial cells. J. Cell Sci. 102, 495–504 (1992).

    CAS  PubMed  Google Scholar 

  27. Silley, P. & Armstrong, D.G. Changes in metabolism of the rumen bacterium Streptococcus bovis H13/1 resulting from alteration in dilution rate and glucose supply per unit time. J. Appl. Bacteriol. 57, 345–353 (1984).

    Article  CAS  PubMed  Google Scholar 

  28. Warner, A.C.I. Nutr. Abstr. Rev. B51, 789–820 (1981).

    Google Scholar 

  29. Malawer, S.J. & Powell, D.W. An imported turbidimetric analysis of polyethylene glycol utilizing an emulsifier. Gastroenterology 53, 250–255 (1967).

    CAS  Google Scholar 

  30. Padgette, S.R. et al. Development, identification and characterization of a glyphosate-tolerant soybean line. Crop Sci. 35, 1451–1461 (1995).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank the Food Standards Agency for supporting this work and we also thank Jay Varma for recruiting the ileostomists.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Harry J Gilbert.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Netherwood, T., Martín-Orúe, S., O'Donnell, A. et al. Assessing the survival of transgenic plant DNA in the human gastrointestinal tract. Nat Biotechnol 22, 204–209 (2004). https://doi.org/10.1038/nbt934

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt934

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing