BIP - Safe use of genetically modified lactic acid bacteria in food. Bridging the gap between consumers, green groups, and industry

The current paper reviews the opportunities that genetically modified lactic acid bacteria may offer the food industry and the consumer and discusses the related food safety topics. To facilitate the introduction of functional foods with proven health claims it is proposed to adapt the current safety assessment procedures (that are laid down in European legislation) for products made by using lactic acid bacteria and genetically modified lactic acid bacteria,

The current European legislation is not completely clear on a number of important scientific matters. For instance, organisms in which the genetic material has been altered by recombinant DNA techniques, e.g. by point mutations or small deletions, are considered to be genetically modified organisms (GMOs), but the market introduction of foods with organisms that have been improved via classical breeding or random mutagenesis is currently acceptable without profound safety analysis. The authors discuss the safety assessment procedures for currently accepted fermented foods and compare these with the procedures for food products fermented with genetically modified (lactic acid) bacteria.

Lactic acid bacteria and genetic engineering

Lactic acid bacteria (LAB) have a long history of use by man for food production and food preservation. LAB are widely used as starter cultures for fermentation of milk, meat and other agro-raw materials. Their properties have been used to manufacture products like cheese, yogurts, fermented milk products, beverages, sausages, and olives. These food-grade bacteria can also improve the safety, shelf life, nutritional value, flavor and quality of the product. An overview of LAB selected after random modifications or directed modifications of DNA is given in Table 1.

The uncontrolled genetic alterations of LAB that occur during random mutagenesis may lead to strains with improved traits. These may be either attractive for the manufacturer of fermented foods, or have benefits for the consumer. However, in the current legislation regarding the use of GMOs in food industry, the nature of the DNA modification dictates the necessity for the novel food product to be subjected to a safety assessment procedure.Spontaneous mutations may occur in LAB cultures by natural events such as insertion sequence elements, radiation, erroneous DNA replication or transcription, and other factors. Strains with ‘natural’ mutations leading to improved fermentation characteristics can be selected by extensive screening of large culture collections. The frequency of mutations can be further increased by exposing LAB to mutagenic conditions such as UV light or chemicals.

An alternative for random mutagenesis is the use of targeted or directed modification of the DNA. Controlled genetic modifications vary from single base pair substitutions, mutations, insertions of genes into the chromosomes, or removal of DNA from the chromosome (deletions) resulting in inactivation of specific enzymes. According to the current legislation, all such directed genetic alterations lead to strains that are considered as GMOs, except for strains obtained by self-cloning, transduction and conjugation. The latter two processes are considered natural events.

Intended and unintended effects

The process of introducing novel traits into LAB by the addition, substitution, removal, or rearrangement of defined DNA sequences could lead to the generation of LAB with novel properties and modified cellular behavior. In addition to the intended effects, also unintended effects, that could be a consequence of the modification, may occur in the newly generated LAB. A distinction can be made between the predictable and unexpected effects that differ in their origin. Predictable effects are a foreseeable and a direct consequence of the intended genetic alterations. Unexpected effects are caused by unintended genetic alterations, or they may occur as a consequence of predictable effects. It should be noted that the occurrence of unintended effects is not restricted to the use of recombinant DNA techniques. Rather, it is likely that unintended effects always occur in the development of strains by traditional (non-recombinant DNA) techniques, or by exposure of micro-organisms to selective pressure or certain environmental conditions, or just by natural events. This would justify that each new natural LAB strain should undergo the same safety assessment procedure as engineered strains. Whether this is a viable approach is currently being investigated by analyzing differences at the global transcriptional level in strains isolated by random mutagenesis and by directed mutagenesis (Renault, 2001). The development of GM-LAB for use in food should be focused on minimizing the occurrence of unintended effects with adverse consequences on human health. Risk assessment studies using new technologies should focus on global response on cellular metabolism as a tool to identify unintended effects, in accordance with the concept of substantial equivalence.

Qualified Presumption of Safety

The low degree of trust by the general public in the (food) industry, in the regulatory authorities and in the scientific community is a major element contributing to the general negative perception of GMOs in the EU. The set up of an infrastructure by the regulatory authorities to subject all fermented food products to a new and profound risk assessment procedure might an important step that is currently needed to convince all parties involved that novel foods are as safe as traditional foods. A distinction within the legislation between food safety assessment procedures for fermented foods (dealing especially with LAB), and GMOs derived from plant and animal origin, would be helpful in the current controversy.

With the exception of those LAB not previously used in the preparation of a human food within the EU, LAB for food use are not subject to EU regulation. Implicit in this absence of any formal requirement for a safety assessment is the recognition that there has been a long history of presumed safe use. The long history of safe LAB usage is in itself an arbitrary criterion and may need further consideration.

As a starting point, the QPS protocol (EU, 2003), based on taxonomy and on the history of safe use of LAB applied in food, could in the near future be applied to any kind of LAB or GM-LAB provided that a series of modern profiling methods are used to verify the absence of unintended effects by altered LAB that may cause harm to the health of the consumer. It is expected that knowledge of genome evolution and profiling studies will reveal that in many micro-organisms the genetic material, that is naturally or spontaneously changed, has been modified more than can be established by directed alterations, including genetic modification. Direct genetic engineering, including self-cloning, generates targeted modifications that can be much better controlled and evaluated than strains that are exposed to random mutagenesis approaches. If such strains are accepted in food fermentations via QPS status, the acceptance by society of GM-LAB obtained via directed genetic alterations could be facilitated.

Cost accountability

The costs associated with the development of novel foods can only be justified in a society that accepts and buys these novel foods. The introduction of traits that decrease production costs for the manufacturer could be the impetus to reduce the price as a way to generate an additional advantage for the consumer.Moreover, the introduction of traits which deliver a direct functional benefit for the consumer, leads to added value of the product that may justify a price increase to the consumer. Furthermore, novel traits could be developed that reduce the environmental burden brought about by the production process. It is expected that any obligation to perform a profound safety assessment, before the launching of any novel food, could significantly add to the initial costs to be made by industry. The question is, who should cover these costs: the industry, the consumer, national authorities, or supra national authorities?

Although each food producer is responsible for the safety of the products placed in the market, in many countries food safety is principally an issue for the regulating authorities. Therefore, it could be proposed that public money is used to set up the complete infrastructure required for food safety assessment as stated in the paragraphs above, including development of modern profiling techniques based on transcriptomics, proteomics, and metabolomics. Consequently, it would also be the task of regulatory authorities to control and monitor the entire safety assessment protocol. On the other hand, the industry is expected to participate as well in the process of assessing safety of novel foods produced with GM-LAB. After approval of the novel food, post market surveillance (see full text) would remain acombined effort for the government and industry.

Labeling

The high costs associated with the development and assessment of novel foods may be a limitingfactor for the industry to develop novel foods, especially those with interesting traits based on health benefits for the consumers. Therefore the industry should be allowed to promote novel foods with scientifically proven advantages over traditional foods by use of labeling and other forms of publicity. Currently the possibilities for promoting scientifically proven functional foods are limited and not harmonized within various EU countries. It is evident that the consumer should be protected by prohibiting the labeling of untrue claims. However, not permitting the labeling of underpinned health claims is equally wrong (Katan and de Roos 2003). The future EU regulation, as proposed in its working paper of 2002 about nutritional and functional claims (EU/SANCO 2002), seems to provide a good solution for both consumer and industry by allowing and regulating the labeling of health claims.

Concluding Remarks

A complex and harmonized legislation and regulation system seems at present times the only correct response to consumer demand for safe food and the related perception that genetically modified micro-organisms in food fermentation are unsafe. In line with current legislation, safety issues should dominate the acceptance of GM-LAB in food fermentation industry. The consequences of development and use of GM-LAB are different compared to GMO from plant or animal origins. The potential intended and unintended effects and related risks can be predicted more accurately and can be verified.

The occurrence of unintended effects is not unique for GM-LAB, but also occurs in LAB used in conventional food fermentations. Logically, this is no reason to ban GM-LAB, but it could be a reason to analyze the unintended effects of traditionally used strains in food fermentation by genomics-based profiling methods. Furthermore, it is recommended to set up governmental sponsored research programs with the ultimate goal of further reducing the uncertainty and mistrust within society towards GM-LAB with beneficial traits. Educating the public on these matters may help to overcome the negative emotions related to the use of certain GMOs.

A further response to the public concern is to strengthen the pre-marketing data requirements and to introduce post-launch surveillance programmes to confirm safety.

In conclusion, broad evaluation of the novel foods derived from GM-LAB could be a starting point to bridge the gap between industry, consumers and green groups. This may lead to acceptance of GM-LAB derived novel foods to provide for a better quality of life in today’s society.

References

European Commission (EU). On a generic approach to the safety assessment of micro-organisms used in feed/food and feed/food production. Working paper. 2003 [cited January 1, 2006]. Available from Internet: http://europa.eu.int/comm/food/fs/sc/scf/out178_en.pdf.

European Commission (EU/SANCO). Regulation of the European Parliament and of the Council on Nutrition, Functional and Health Claims Made on Foods. Working document SANCO/1832/2002, 2002. [cited January 1, 2006]. Available from Internet: http://www.foodstandards.gov.uk/multimedia/pdfs/draftregsonclaims.pdf.

KATAN, Martijn B. and DE ROOS, Nicole M. Toward Evidence-Based Health Claims for Foods. Science, January 2003, vol. 299, no. 5604, p. 206-207. [CrossRef]

RENAULT, Pierre. Expression profiles as fingerprints for the safety evaluation of new strains, including GMOs used in bioprocessed food (EXPRESS-FINGERPRINTS). EU funded project, QLK3-2001-01473. 2001.