“Both/and” antibiotic alternatives: Beneficial feed additives that target the host immunometabolic interface

     

Significant research and development has been committed to finding alternatives to antibiotics that are at least as effective as conventional antibiotics in preventing disease and promoting growth. It has been well known for 70 years that antibiotics have this dual disease/growth effect. However, it was only around the turn of the century that consideration of antibiotic host effects on growth and immunity were significantly studied. The sequence of events beginning with antibiotic restrictions in animal production, the advent of immunometabolism approaches in animal agriculture in the past 10 years, and the understood need for knowledge of mechanism of action for feed additives have led to an explosion in the study of antibiotic alternatives. Our laboratory approaches these studies with a functional proteomic approach and immunometabolic perspective. Given the disease resistance/growth promotion functions of antibiotics and the unseverable link between immunity and metabolism, it follows that the most effective antibiotic alternatives would affect host and microbe. Here, we describe the dual mechanism of action of 2 feed additives, butyrate and a postbiotic with fermentate. Unlike probiotics, postbiotics containing fermentate will include metabolites and immune stimulatory factors in a single product; these can impact numerous physiological points along the gut. The bioavailable metabolites feed the host metabolism while the microbial components stimulate immune activity. This dual nature of postbiotics is a closer analog to antibiotics than a feed additive targeting a single mechanism. With regard to butyrate, depending on the metabolic status of the host, the fate and effect of butyrate can be distinct. Depending on the immunometabolic context, butyrate can feed oxidative phosphorylation or modify gene expression by directly modifying histones. This dual nature may explain the often-conflicting findings in the literature regarding butyrate efficacy and function. The ultimate determinant of feed additive efficacy under diverse production conditions may be that it is both antimicrobial and host enhancing.

Key Words: Immunometabolism, feed additives, dual action.