when individuals whose digestive system has been compromised by disease, injury, or advanced age ingest foods containing bioactive proteins or peptides.

The digestive epithelium of newborn infants permits the transient absorption of whole proteins or large protein fragments until closure of the gut epithelium occurs. Closure is facilitated by breastfeeding and delayed in infants that are formula fed. The timing of the closure might range from weeks to months, depending on dietary factors. Prior to closure, a wide variety of intact proteins might cross the digestive epithelium by a non-selective mechanism and enter the bloodstream. Thus, consumption of food (especially milk) containing bioactive proteins or peptides could result in the transfer of such molecules into the bloodstream of newborn infants. This possibility raises a concern regarding recombinant bioactive molecules present in milk used in infant formulas.

Bioactive peptides and proteins also might exert their effects in the digestive system, prior to absorption. For example, recombinant human bile-salt stimulated lipase (BSSL) has been expressed in the milk of transgenic sheep; this protein is intended for oral administration as a therapeutic agent for treating patients suffering from pancreatitis (PPL Therapeutics, 2001). Consumption of food products (i.e., milk and meat) from animals expressing bioactive molecules such as BSSL could alter digestion in otherwise healthy individuals, and presents a food safety concern. Lysostaphin, a bactericidal protein expressed by certain bacteria, has been expressed in murine milk, where it reduced mastitis caused by Staphylococcus aureus (Kerr et al., 2001). Transgenic cattle expressing lysostaphin in milk have been generated with the intent of reducing mastitis in that species (Suszkiw, 2001). Similarly, Jia et al. (2000) proposed production of transgenic fish expressing the hybrid antimicrobial peptide cecropin-melittin for control of fish pathogens. Preliminary studies using injections demonstrated the effectiveness of the antimicrobial peptide to protect fish against infections and suggested that the strategy of overexpressing the peptides in transgenic fish might provide a method of decreasing bacterial disease problems in fish. Milk containing lysostaphin or fish expressing cecropin-melittin could alter the balance of digestive tract flora of consumers of these products; in addition, widespread use of such antimicrobial agents also could foster the emergence of lysostaphin-resistant strains of pathogenic S. aureus or Vibrio anguillarum. Thus, food products containing antimicrobial proteins might present a food safety concern in view of their potential to alter the balance of consumers’ intestinal flora, and might foster the evolution of microbial strains resistant to specific agents.

Many genetically engineered fish and shellfish express an introduced growth hormone (GH) gene—most often a fish GH gene—in order to promote rapid growth. Hence, it is particularly important to make sure that such a transgene product has no biologic activity in humans or animals that consume fish or shellfish expressing such a transgene. The food safety of GH proteins was evaluated when administration of recombinant bovine GH (rbGH, also

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