Development of Novel Technologies for Swine Production

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The swine production industry operates under a narrow profit margin that has tightened in recent years due in part to increasing governmental regulations, Chad Stahl said in his presentation to the Carolina Feed Industry Association Fall Conference and published in NCSU Swine News Volume 31, Number 01.

Two areas of regulatory activity that he said he felt pose significant current or near future threats to the profitability of swine production are those related to the environmental impact of swine production and the use of sub-therapeutic levels of antibiotics in swine feed. My research group focuses its efforts on developing new technologies to allow the U.S. swine production industry to remain profitable under this changing regulatory milieu.

Concerns over the environmental impact of phosphate from swine excreta, which led to EPA regulations (Federal Register, 2003) limiting the amount of phosphate (P) that can be applied per unit of land, has driven research towards finding ways to reduce the need for inorganic P supplementation in swine diets as well as reducing the excretion of P by these animals. This research led to the discovery and development of multiple phytase enzymes and phytase expression systems (reviewed by Lei and Stahl, 2001). Now that there is sufficient competition in the phytase market to ensure the price competitiveness of these enzymes, innovative work is needed to further reduce the environmental impact of swine production. Very little work has examined the influence of genetics, with the exception of genetic P regulatory diseases, on P nutrition in any species. Hittmeier et al. (2006) demonstrated that the metabolic response to a severe dietary P deficiency was modulated by genetic background in young pigs. Interest in further reducing the environmental impact of swine production has fueled the need for a better understanding of the effects of subtle P deficiency and how genetics may mediate these effects.

Both global and targeted gene expression analysis were utilized in order to identify targets for genetic polymorphism analysis (Hittmeier et al., 2006; Qu et al., 2007). From this work, we have identified a polymorphism that appears to be associated with altered use of dietary phosphate in pigs (Figure 1). Additionally, the response of pigs from these different genotypes to minor dietary phosphate restriction is different.

In a smaller, more intensive study, pigs of the 11 genotype were found to be more susceptible to a minor dietary phosphate deficiency (20% less available P based on NRC, 1998). This was seen based on several measures of bone integrity and ash percentage (Figure 2). Despite demonstrating greater sensitivity to dietary phosphate deficiency based on measures of bone integrity and plasma hormone levels, these 11 genotype animals did not demonstrate any significant differences in growth performance. Differences such as these demonstrate the need to define P needs based on genetic background for the swine production industry. Understanding the underlying genetic mechanisms that regulate P utilization may lead to novel strategies to produce more “environmentally-friendly” pigs.

An additional area of potential increased governmental regulation is the use of sub-therapeutic levels of antibiotics in swine feed. The prophylactic and growth-promoting use of antibiotics in animal agriculture has been greatly scrutinized in recent years, due to concerns regarding its role in contributing to antibiotic resistance. Worldwide concern over this use of antibiotics and its contribution to the spread of antibiotic resistance has led to increased regulation over the use of antibiotics in animal agriculture (FDA, 1999; FDA 2003; WHO, 2000), and will likely continue toward a zero tolerance for the use of prophylactic or growth promoting antibiotic use in animals. The World Health Organization states in their “Global Principles for the Containment of Antimicrobial Resistance in Animals Intended for Food” (WHO, 2000) that the prophylactic use of antibiotics needs to be dramatically reduced if not stopped. It has been estimated that a complete ban on the use of antimicrobials in swine production would increase production costs by more than $6 per pig (Hayes et al., 1999). With the current regulatory milieu in mind and for the sustainability of animal agriculture, alternatives to conventional antibiotics have to be developed to improve animal health and production efficiency. His research group focused on utilizing biotechnology to produce protein-based alternatives to conventional antimicrobials utilized in animal feed. Specifically, his research group has been examining the potential of a class of bacteriocins that are produced by Escherichia coli, and are effective against pathogens of concern for both animal health and human food safety (Stahl et al., 2004; Callaway et al., 2004; Patton et al., 2007). Recently, he said they had shown that when included at low levels (< 20mg/kg of diet) in the diets of weanling pigs, a colicin can prevent experimentally induced post-weaning diarrhea caused by F18 positive E. coli strains (Cutler et al., 2007). Pigs receiving the colicin in their diet had higher (P < .05) average daily gain and feed efficiency than the control pigs (Table 1). The colicin-treated pigs also demonstrated no incidence of diarrhea, compared with greater than 60 percent of the control animals having diarrhea (Figure 3). Utilizing a protein-based alternative to conventional antibiotics in swine diets has several advantages. They are not related to any antibiotics that are currently being used in human medicine, they would not be absorbed intact by the animals; thereby eliminating concerns over antibiotic residues in meat, and colicins could be effective at low enough concentrations so as not to significantly alter the nutrient density of the diet.

By focusing our efforts on understanding the genetic mechanisms that underlie phosphate utilization as well as developing novel antibiotics for use in swine feed, his research group hopes to improve the economic success and sustainability of the swine production industry. References

• Callaway, T. R., C. H. Stahl, T. S. Edrington, K. J. Genovese, L. M. Lincoln, R. C. Anderson, S. M. Lonergan, T. L. Poole, R.B. Harvey, and D. J. Nisbet. 2004. Colicin concentrations inhibit growth of Escherichia coli O157:H7 in vitro. J. Food Prot. 67(11):2603-2607.
• Cutler, S. A., S. M. Lonergan, N. Cornick, A. K. Johnson, and C. H. Stahl. 2007. Dietary inclusion of Colicin E1 is effective in preventing Escherichia coli F18 post-weaning diarrhea in pigs. Antimicrob. Agents Chemother. 51(11): 3830-3835.
• U.S. Food and Drug Administration (FDA). 1999. Guidance for Industry #78: Consideration of the Human Health Impact of the Microbial Effects of Antimicrobial New Animal Drugs intended for Use in Food-Producing Animals. CVM/FDA/DHHS.
• FDA, 2003. Guidance for Industry #152: Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern. CVM/FDA/DHHS.
• Hayes, D. J., H. H. Jensen, L. Backstrom, and J. Fabiosa. 1999. Economic impact of a ban on the use of over-the-counter anitibiotics in U.S. swine rations (pp. 25-27). Ames, IA: Iowa State University.
• Lei, X. G., and C.H. Stahl. 2001, Nov. Biotechnological development of effective phytases for mineral nutrition and environmental protection. Appl Microbiol Biotechnol. 57(4):474-481.
• Patton, B. S., J. S. Dickson, S. M. Lonergan, S. A. Cutler, and C. H. Stahl. 2007. Inhibitory activity of Colicin E1 against Listeria monocytogenes. J. Food Protection 70(5): 1256-1262.
• Stahl, C. H., T. R. Callaway, L. M. Lincoln, S. M. Lonergan, and K. J. Genovese. 2004. Evaluation of colicins for inhibitory activity against Escherichia coli strains responsible for post-weaning diarrhea and edema disease in swine. Antimicrob. Agents Chemother. 48(8): 3119-3121.
• World Health Organization (WHO). 2000. WHO Global Principles for the Containment of Antimicrobial Resistance in Animals Intended for Food: Report of a WHO Consultation. Geneva, Switzerland: WHO/CDS/CSR/APH.