March 01, 2003


 Gut warfare

Competitive exclusion research heats up

Posted Feb. 15, 2003


The topic of whether the government should further limit antimicrobial use in food animals continues to make news. For veterinarians and producers, the possibility of a further ban is unsettling, but what if it happens? What are the alternatives?

For several years, researchers have been investigating the use of natural products to prevent and treat disease, as well as promote growth. Some of these efforts have shed light on promising products such as genistein, conjugated lineoleic acid, and distiller's dried grains with solubles (see JAVMA, Sept, 15, 2002, page 766).

Other researchers think possible solutions may lie in the gut of the very animals they are trying to help. They are developing beneficial bacterial cocktails that can wage war against troublemaking bacteria. These cocktails are based on the concept of competitive exclusion, a scenario where good bacteria compete with harmful bacteria, either by competing for nutrients, competing for attachment sites, or producing antibacterial molecules against undesirable bacteria. Researchers obtain hearty disease-fighting bacteria from the digestive tracts of animals, create cultures, and then administer these to other animals in the same species.

Competitive exclusion was first proven in 1973, and, in Europe, competitive exclusion products have been on the market for over 10 years. Only one product, however, is on the U.S. market: PREEMPT was approved in 1998 for reducing the incidence of Salmonella infection in chickens. So why is there just one?

In Europe, defined and undefined cultures are allowed on the market. In the United States, however, competitive exclusion products must adhere to Food and Drug Administration regulations, which require bacterial mixtures to be well defined.

According to officials at the FDA Center for Veterinary Medicine's Office, "In order to consider competitive exclusion products safe, CVM needs to have an understanding of their composition, including the identity of the major organisms present. There must be a demonstrated relationship between the identified organisms and product efficacy. CVM must be satisfied that human pathogens and known transferable resistance factors are not present."

Patenting an undefined product could also cause some problems if other companies bring similar products to the FDA in the future.

The FDA defines competitive exclusion products as products containing live microorganisms isolated from the gastrointestinal tract of chickens and other animals, and labeled and/or promoted with therapeutic and/or structure/function claims with statements about reductions in enteric pathogens.

The bacteria used in competitive exclusion cultures can originate only from the animal that it is intended to treat, explains Robin Anderson, PhD, a research microbiologist at the Food and Feed Safety Research Unit of the Department of Agriculture's Agricultural Research Service, College Station, Texas.

Competitive exclusion products differ from direct-fed microbial products, which may be regulated as food and consist of specific organisms, such as Lactobacillus acidophilus, that are listed in the Association of American Feed Control Officials' official publication.

In recent years, research into competitive exclusion products has heated up, and people are getting excited. A 2001 congressional report stated: "Competitive exclusion products offer an innovative and valuable approach to reducing Salmonella and other harmful bacteria in poultry and livestock."

The report also recommended that, in view of the significant public health benefits of competitive exclusion products, the FDA should review new animal drug applications for these products on an expedited basis.

"Competitive exclusion is another, safer weapon in the arsenal to fight harmful bacteria," says Dr. Billy Hargis, director of the Poultry Health Laboratory at the University of Arkansas in Fayetteville.

Dr. Hargis' research team is looking at protecting poultry from Salmonella by administering beneficial bacteria to young chickens. His research team has screened numerous bacteria for efficacy, has identified roughly 20 bacteria that fit the bill, and has a patent pending for their cocktail.

Dr. Roger Harvey, a veterinary medical officer who works with Dr. Anderson at the USDA, is developing a CE culture for young pigs.

"The CE product seems to lessen colonization rates and mortality from Salmonella and Escherichia coli in young pigs," Dr. Harvey said. "We have completed field trials with about 30,000 pigs, and the results look good. We are averaging about 1.5 percent to 2 percent mortality from all causes in our treated pigs, compared with 5 to 10 percent in the untreated pigs."

Research has also shown benefits for food safety in cattle. Michael Doyle, PhD, director of the Center for Food Safety at the University of Georgia, has developed a culture for cattle that is successful at reducing E coli O157:H7. "The organism is no longer detectable after two to three weeks in 80 percent to 90 percent of the animals," Dr. Doyle said.

These researchers are all in different stages of seeking approval from the FDA, and competitive exclusion research is ongoing at several other institutions.

The FDA-CVM's Office of New Animal Drug Evaluation encourages the development of safe and effective competitive exclusion products. According to CVM officials, competitive exclusion products are best described as one tool in an ever-growing tool bag of human food safety tools. While they are one of several new technologies that have a niche in reducing zoonotic enteric pathogens, they are not intended to be a replacement for antimicrobial products. Antimicrobial drugs fulfill a wide variety of therapeutic and production needs in animals.

Competitive exclusion products can, however, help reduce the number of antimicrobials used in food animals. They offer a potential way of replacing growth promoting antibiotics and reducing the use of therapeutic antimicrobials, Dr. Harvey says.

This is good news for those worried about rising antimicrobial resistance. "It opens possibilities for a whole new paradigm of preventing and treating enteric bacterial diseases in domestic animals," Dr. Hargis said. "I think that it is really exciting."