The sub-inhibitory theory for antibiotic growth promoters

Abstract

Antibiotics have played a critical role in the prevention, control, and treatment of bacterial diseases in humans and animals, and as growth promoters (AGPs) when used at sub-therapeutic concentrations in animal production. Numerous hypotheses have been proposed for the effectiveness of AGPs, which have largely centered on the beneficial modulation of the intestinal microbiota. However, these hypotheses have been doubted by some researchers, as AGPs are fed at concentrations that would typically be below minimum inhibitory concentrations (sub-MIC) for the antibiotic used. More recently, pro-inflammatory immune responses have been associated with poor growth performance, and this, along with reported direct, anti-inflammatory effects of some antibiotics, have led to suggestions that reducing the nutrient cost of (intestinal) inflammation may explain the growth promoting or permitting effect of AGPs. However, doubts about antibacterial effects of AGPs, and the search for alternative explanations, overlook the sub-MIC effects of antibiotics. This paper summarizes some of the reported sub-MIC effects of antibiotics and considers these in the context of helping to explain the mode of action of AGPs and effects seen in studies in vivo. This leads to suggestions for the features that alternatives to AGPs could exhibit to achieve similar performance efficacy as AGPs.

Effects of phytogenic feed additives on cellular oxidative stress and inflammatory reactions in intestinal porcine epithelial cells1

“…It is further hypothesized that the growth promoting effect is based on inflammation-restricting characteristics of the AGP ( Niewold, 2007 ). Although an anti-inflammatory activity of various AGP is corroborated by several authors ( Kroismayr et al, 2008 ; Khadem et al, 2014 ; Palamidi et al, 2016 ), the opinions still differ regarding their real mode of action ( Broom, 2017 ). Because there is evidence of anti-inflammatory activity of several macrolides (e.g., tylvalosin, tilmicosin, and TYL) on immune cells ( Cao et al, 2006 ; Buret, 2010 ; Zhao et al, 2014 ), we included the APG TYL in tests on NF-κB and the inflammatory target genes.…”

Gut immunity: its development and reasons and opportunities for modulation in monogastric production animals

“…Lee et al (2012) reported that feeding antimicrobials (decoquinate and monensin) to broiler chicks between 1 and 43 DOA altered the percentages of MHCII+ and CD4+ intestinal intraepithelial lymphocytes and their expression of various cytokines and chemokines compared with untreated controls. While direct effects of antimicrobials on gut immune-related cells, even at sub-therapeutic concentrations, is possible (Niewold, 2007), it is more likely that these effects are mediated through changes to the intestinal microbiome (Broom, 2017).…”

Impacts of antibiotic reduction strategies on zootechnical performances, health control, and Eimeria spp. excretion compared with conventional antibiotic programs in commercial broiler chicken flocks

“…The advantages of using antibiotics as growth promoters have been extensively studied and reviewed ( Jones and Ricke, 2003 ; Dibner and Richards, 2005 ). Although the exact mechanism of action still needs to be elucidated, the administration of subtherapeutic doses of antibiotics in chickens' diet is believed to alter the intestinal microbiota to improve feed efficiency ( Broom, 2017 ). Because various antibiotics will have different effects on the bacterial membership in the ceca ( Costa et al., 2017 ), the exact microbiota composition that leads to increased performances with the use of antibiotic growth promoters is still unclear.…”