Science in Society Archive

Important Books & Reports

Banishing Glyphosate

Banishing Glyphosate - Dr. Eva Sirinathsinghji, Dr. Mae-Wan Ho and others

Glyphosate/Roundup, falsely claimed by Monsanto to be safe and harmless, has become the world’s most widely and pervasively used herbicide; it has brought rising tides of birth defects, cancers, fatal kidney disease, sterility, and dozens of other illnesses - more

Ban GMOs Now

Ban GMOs Now - Dr. Mae-Wan Ho and Dr. Eva Sirinathsinghji

Health & environmental hazards especially in the light of the new genetics - more

Living Rainbow H2O

Living Rainbow H2O - Dr. Mae-Wan Ho

A unique synthesis of the latest findings in the quantum physics and chemistry of water that tells you why water is the “means, medium, and message of life” - more

The Rainbow and the Worm - the Physics of Organisms

The Rainbow and the Worm - the Physics of Organisms - Dr. Mae-Wan Ho

“Probably the Most Important Book for the Coming Scientific Revolution” - more

Ban GM Probiotics

Beneficial bacteria living in the human gut are now subject to extensive genetic modification that could turn them into pathogens. Prof. Joe Cummins and Dr. Mae-Wan Ho call for a ban on releases of GM probiotics

Probiotics for health

'Probiotics' are naturally occurring beneficial bacteria found in the human gut, and are being added to food for their health-promoting effects. The probiotics studied most extensively are Bifidobacterium and Lactobaccilus, both derived from fermented milk products. The efficacy of probiotics has been clearly established in recent years. For example, double blind, randomized trials with probiotics added to milk reduced respiratory infections and the severity of illness among children in a day care setting [1]. Another study showed that probiotic treatment relieved diarrhea in children [2].

This success has attracted the attention of genetic engineers, who want to "improve" on the successful applications, which probably date back to the beginning of written history.

The cross-talk between the human host and the gut bacteria has evolved over millions of years. Its contributions to the health of the human host depend on an intricate network of bacteria-bacteria and bacteria-host interactions that, if thrown out of balance, will very likely result in disease [3].

Can GM "improve" probiotic bacteria without turn them into dangerous pathogens?

Probiotic bacteria modulate the immune system and provide an ecological balance in the gut that excludes disease-causing microbes. Germ-free mice bred in the laboratory have less immune cells, and tend to leak more food antigen across the intestinal barrier. These conditions improve after about a month of exposure to bacteria [4]. Probiotic bacteria must not be pathogenic, however; and it is essential for probiotic treatments to be tested for safety. The vast majority of applications have been free of pathological outcomes; but there has been one case of local infection from a rogue Lactobacillus strain [5]. The prospect that genetic modification might "improve" probiotic microbes must be seriously balanced against the potential of turning harmless, beneficial microbes into dangerous pathogens ("No biosecurity without biosafety", ISIS report 16 March 2005), particularly in the case of bacteria that naturally inhabit the human gut.

The complete genome sequence of the probiotic Lactobacillus acidophilus has been determined and features contributing to survival in the gut and promoting interactions with the intestines have been identified [6]. The genome sequence of Bifidobacterium longum, similarly, reflects its adaptation to the human gastrointestinal tract including potential immuno-modulating proteins [7]. Milk-fermenting bacteria harbor bacteriophages (viruses), including those that cause diseases, and 'temperate phages' capable of integrating their viral genome into the bacterial genome [8]. Temperate bacteria phages play an important role in horizontal gene transfer among bacteria residing in the same environment, in this case, the human gut.

Genetic modification of bacteria can be done by DNA transformation (direct uptake of DNA), transduction (transfer of genes by temperate bacterial phage) or by the use of plasmids (small circular DNAs that replicate with the bacterial cell but stay outside the bacterial chromosome). Normally, transgenes are propagated in bacteria in plasmids because DNA transformation is not successful unless the DNA shares homology (sequence similarity) with the bacterial chromosome.

Lactic acid bacteria (Lactobacillus spp) have been genetically modified to increase proteolytic activity, to resist viruses, to metabolize complex carbohydrates or to enhance metabolism. The only modified lactic acid bacterium approved under the EU directive so far is a strain with a modified luciferase gene to detect antibiotic residues in milk, but that strain does not enter the food chain because it is used on a small test sample of milk that is then destroyed.

Dangerous experiments with probiotics

It has been suggested that a random 'gene-shuffling' technique should be employed to improve lactic acid bacteria for use as probiotics [9]. Gene-shuffling is an inherently hazardous procedure that can generate millions of recombinant bacteria in a matter of hours; it will be impossible to predict how many of those might be lethal pathogens ("Death by DNA shuffling", SiS 18 http://www.i-sis.org.uk/isisnews.php).

A United States patent application for recombinant lactic acid bacteria for treating allergy includes fermented milk product (yogurt) containing lactic acid bacteria modified with synthetic genes specifying epitope IgE antibodies (allergy antibodies) on the surface of the bacterium. Allergy therapy would include eating the recombinant yogurt to suppress the allergy as the natural allergen is encountered [10]. This kind of 'therapy' must be treated with extreme caution. Experience tells us that interfering with the immune system can lead to nasty surprises, as in the case of the harmless mousepox virus that turned into a lethal pathogen when a gene that was supposed to boost antibody production was inserted into it [11]. In another experiment, a Lactobacterium strain of human origin was modified with a gene for tetanus toxin to produce antigen to immunize against tetanus. The recombinant lactic acid bacterium was delivered as a nasal spray to provide a strong immunization [12]. No consideration has been given to the distinct possibility that the tetanus toxin gene could easily be passed along to a pathogen.

Genetic engineers are also identifying Bifidobacteria probiotic strains and thinking of 'enhancing' them by genetic modification. Plasmid vectors belonging to Bifidobacteria or shuttle plasmid vectors for transferring genes between E. coli and Bifidobacteria are being used, so far, to study the role of Bifidobacteria in the gut ecosystem rather than in the production of modified probiotic strains [13]. The instability of recombinant plasmids has proved an obstacle to industrial exploitation of GM Bifidobacteria [14]. Furthermore, gene transfer was observed in the digestive system of previously germ free mice between Lactobacteria and Bifidobacteria [15], suggesting that GM probiotic strains would alter the entire microbial ecology of the digestive tract in an unpredictable manner.

A recent review stressed the huge market for probiotics in Europe, pointing to the value of molecular genetic technology in characterizing and identifying many probiotic microbes [16]. An earlier review discussed bacterial replacement therapy as a form of "germ warfare" to prevent and control infections of skin, oral cavity, ears and uro-genital tract. The friendly probiotic bacteria are used to colonize the gut microflora to eliminate or minimize pathogens from establishing themselves. That approach has proved successful in controlling dental caries, ear infections and streptococcal diseases. In some rare instances, the "friendly" bacteria had antibiotic resistance markers or were genetically modified [17].

No GM bacteria must be allowed for probiotic use

The study of bacteria colonizing the human gut has only just begun. There are ten times more bacteria than there are cells in the intestine, consisting of more than 400 different species; the overwhelming majority of the species still unknown. Prof. Tore Midtvedt, who pioneered the use of germ-free mice to study gut bacteria, was among the first to demonstrate the importance contribution of individual bacteria to the development of the immune system of the gut [18]. In view of our vast ignorance of gut ecology, we cannot allow genetically modified probiotic bacteria to be used, unless and until we fully understand the intricate ecological balances that have co-evolved with the human species. There should be a ban on the use of any GM probiotic bacteria in human subjects.

Article first published 22/04/05



References

  1. Hatakka K, Savilahti E, Ponka A, Meurman JH, Poussa T, Nase L, Saxelin M. and Korpela R. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial BMJ 2001,322,1327-33.
  2. Friedrich M. A bit of culture for children:probiotics may improve health and fight disease JAMA 2000, 284,1365-9.
  3. Hart A, Stagg A, Frame M, Graffner H, Glise H, Falk P and Kamm M. The role of the gut flora in health and disease, and its modification as therapy Aliment. Pharmacol. Ther. 2002,16,1383-93.
  4. Teitelbaum J and Walker A. Nutritional impact pre- and probiotic as protective gastrointestinal organisms. Ann.Rev. Nutr. 2002, 22,107-38.
  5. Saarela M, Matto J and Mattila-Sandholm ,T. Safety aspects of Lactobacillus and Bifidobacterium species originating from human oro-gastrointestinal tract or from probiotic products. Microbial Ecology in Health and Disease 2002,14, 233-40.
  6. Altermann E, Russell M, Azcarate-Peril A, Barrangou R, Buck B, McAuliffe O, Souther N, Dobson A, Duong T, Callanan M, Lick S, Hamrick A, Cano R and Klaenhammer T. Complete genome sequence of the probiotic lactic acid bacterium Lactobacillus acidophilus NCFM. Proc Natl Acad Sci U S A. 2005,102,3906-12.
  7. Schell M, Karmirantzou M, Snel B, Vilanova D, Berger B, Pessi G, Zwahlen M, Desiere F, Bork P, Delley M, Pridmore R and Arigoni F. The genome sequence of Bifidobacterium longum reflects its adaptation to the human gastrointestinal tract. Proc Natl Acad Sci U S A 2002, 99, 4422-7.
  8. Brussow H. Phages of dairy bacteria Annu Rev Microbiol. 2001, 55, 283-303.
  9. Ahmed ,F. Genetically modified probiotics in food Trends in Biotechnology 2003, 21, 491-7.
  10. Stadler B,Vogel M, Edouard-Jacques G, and Frische R. Lactic acid bacteria as agents for preventing allergy United States Patent Application 2004, 20040265290.
  11. Nowak R. Disaster in the making. New Scientist 2001: 13 Jan. 4-5.
  12. Grangette C, Muller-Alouf H, Goudercourt D, Geoffroy M, Turneer M and Mercenier A. Mucosal immune responses and protection against tetanus toxin after intranasal immunization with recombinant Lactobacillus plantarum. Infect Immun. 2001, 69,1547-53.
  13. van der Werf . and Venema K. Bifidobacteria: Genetic modification and the study of their role in the colon. J Agric Food Chem 2001, 49, 378-83.
  14. Gonzalez Vara A, Rossi M, Altomare L, Eikmanns B and Matteuzzi D. Stability of recombinant plasmids on the continuous culture of Bifidobacterium animalis ATCC 27536. Biotechnol Bioeng. 2003, 84,145-50.
  15. Gruzza M, Fons M, Ouriet M, Duval-Iflah Y and Ducluzeau R. Study of gene transfer in vitro and in the digestive tract of gnotobiotic mice from Lactococcus lactis strains to various strains belonging to human intestinal flora. Microb Releases 1994, 2,183-9.
  16. Saxelin M, Tynkkynen S, Mattila-Sandholm T. and de Vos W. Probiotic and other functional microbes: from markets to mechanisms Current Opinion in Biotechnology, In Press 2005 doi:10.1016/j.copbio.2005.02.003
  17. Tagg J and Dierksen K. Bacterial replacement therapy: adapting germ warfare to infection prevention. Trends in Biotechnology 2003, 21, 217-23.
  18. Freitas M, Aexlsson LG, Cayuela C, Midtvedt T, Trugnan G. Microbial-host interactions specifically control the glycosylation pattern in intestinal mouse mucosa. Histochem Cell Biol 2002, 118, 149-61.

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