Pre-Treatment with Bromelain Prevents Intestinal Dysbiosis in Pigs with Post-Weaning Diarrhea, without Increasing Antimicrobial Resistance in Escherichia coli

SIMPLE SUMMARY: Antimicrobials are commonly used to prevent diarrhea and poor growth in the first two weeks after pigs are weaned, but they also produce side effects including the emergence of antimicrobial resistance and the destruction of protective bacteria that can exclude pathogens. Bromelain, an enzyme extract from plants, blocks attachment of the pathogen Escherichia coli to host cells, so it was evaluated against neomycin and zinc oxide for the prevention of diarrhea, reduction in pathogenic E. coli, disruption of the gut bacterial population and the emergence of antimicrobial resistance. All treatments prevented diarrhea in weaner pigs, but only bromelain was able to maintain the stability of the gut bacterial population and prevent the emergence of antimicrobial resistance in gut bacteria. On-farm studies have shown that bromelain can prevent post-weaning diarrhea, but this is the first study to show bromelain’s ability to stabilize gut bacterial populations in the critical post-weaning period. Bromelain treatment, in combination with probiotics, good hygiene and low-protein diets, may reduce the reliance on antibiotics and heavy metals for preventing post-weaning diarrhea, which will ultimately benefit both pig and human health. ABSTRACT: Pigs are especially vulnerable to intestinal pathogens and dysbiosis in the first two weeks after weaning. Infection with enterotoxigenic strains of Escherichia coli (ETEC) in combination with poor nutrition and hygiene can lead to diarrhea, poor growth and increased mortality. While neomycin and zinc oxide can prevent post-weaning diarrhea (PWD), their broad-spectrum activity also kills commensal microbiota and can lead to the emergence of heavy metal and antimicrobial resistance. Bromelain prevents attachment of F4 ETEC to intestinal enterocytes by cleaving the host receptor. In controlled environmental facilities, weaned pigs treated with either therapeutic levels of neomycin sulfate, zinc oxide, bromelain or non-treated were monitored for diarrhea, weight gain, feed intake, feed efficiency, excretion of F4 ETEC, changes to their intestinal microbiomes and antimicrobial resistance in E. coli. The treatment effects were evaluated at weaning, during two weeks of treatment and for three weeks after treatments ceased. Minimal clinical signs of PWD were observed, except in zinc-treated pigs post treatment. Intestinal dysbiosis was observed in response to diarrhea and in pigs treated with both neomycin and zinc. Antimicrobial resistance increased in commensal E. coli isolated from neomycin- and zinc-treated pigs. In contrast, bromelain controlled PWD and prevented intestinal dysbiosis without inducing antimicrobial resistance.