EVALUATION OF A BERBERINE AS AN ALTERNATIVE TO ANTIBIOTICS IN NURSERY PIG DIETS

Our goal is to determine the effects of using berberine (an alkaloid, present in various plant species including Berberis aquifolium [Oregon grape] and Berberis aristata [tree turmeric]) as an alternative to antibiotics in diets for food animals, using the weaned pig as model. Our central hypothesis is that berberine will be a suitable alternative to antibiotics in improving gut health of weaned pigs. Our hypothesis has been formulated, in large part, based on our own preliminary research demonstrating that berberine improved growth performance of weaned pigs. In a preliminary trial, dietary inclusion of berberine at 0.06% improved the average daily gain of weaned pigs (weaned at 21 days of age) by 16.7% during the first 3 weeks post-weaning. Others reported that berberine reduced ETEC-induced diarrhea in humans, castor oil-induced diarrhea in mice, and irritable bowel syndrome-induced diarrhea in humans. Additionally, others have shown that berberine exhibits antioxidant activity, which suggests that it can alleviate oxidative stress. Intestinal permeability of piglets increases immediately after weaning due to increased oxidative stress. Increased intestinal permeability increases translocation of toxins such as lipopolysaccharides that are produced by gut microorganism into the body, causing inflammatory injuries in the gut wall. Inflammatory injury is a characteristic of most gut infections, implying that the increased susceptibility to gut infections of pigs after weaning is mainly due to increased intestinal permeability to toxins and hence inflammatory injury. Together, these results suggest that berberine can improve the gut health of weaned pigs by reducing permeability of the gut to toxins through reduction of oxidative stress. Indeed, berberine reduced lipopolysaccharide-induced injury in intestine, ischemia-reperfusion-induced tight junction injury, and polymicrobial sepsis-induced damage to intestinal mucosal barrier in rats. Berberine is already commercially available and can easily be extracted from the Oregon grape trees, which grow abundantly in the western part of the USA. Thus, berberine could easily be used as an alternative to antibiotics in diets for weaned pigs.Our first objective is to identify the optimal dietary level of berberine that results in improved gut integrity and growth performance of weaned pigs. In our preliminary study, inclusion of berberine in diets for weaned pigs at 0.06% improved their growth performance, but the magnitude of improvement was a half that of dietary antibiotics (16.7 vs. 32.6%). We hypothesize that dietary berberine at >0.06% will result in greater improvement in gut integrity and growth performance of weaned pigs. However, berberine is bitter, and hence its dietary inclusion at high levels can reduce diet palatability. Indeed, we observed reduced feed intake by weaned pigs due to dietary berberine at 3%. Thus, there is a need to identify dietary levels of berberine that result in improved gut integrity and growth performance of weaned pigs without having a negative effects on voluntary feed intake.Our second objective is to determine the effect of dietary berberine on gut microbial composition and the growth performance of E. coli-challenged weaned pigs. An E. coli challenge is selected to represent a greater environmental bacterial load associated with commercial swine facilities as compared to a university research facility. University research facilities are typically considered more "clean" environments compared to commercial swine facilities. The response of pigs to antibiotic alternatives can decrease with increase in cleanliness of the environment in which they are weaned and housed. Hence, results obtained from pigs housed in a "clean' environment may not be applicable to pigs housed in a "dirty" environment. Secondly, post-weaning diarrhea is quite variable among pigs, and it is affected by many factors including the genetics of the pigs. Results obtained from E. coli-challenged pigs housed in the "clean' university research facilities are applicable to pigs housed in the "dirty" commercial swine barns, and the variability in severity of diarrhea among E. coli-challenged pigs is low. Therefore, a standardized E. coli-challenged pig model can be used to study the effect of antibiotic alternatives on gut health and performance of pigs weaned and housed in clean environments. The dietary level of berberine in Objective 2 will be dependent of the results from Objective 1.