Overall assessment of antibiotic substitutes for pigs: a set of meta-analyses

BACKGROUND: Antibiotic growth promoters are widely used to improve weight gain. However, the abuse of antibiotics can have many negative effects on people. Developing alternatives to antibiotics is an urgent need in livestock production. We aimed to perform a meta-analysis and network meta-analysis (NMA) to investigate the effects of feed additives as potential antibiotic substitutes (ASs) on bacteriostasis, growth performance, intestinal morphology and immunity. Furthermore, the primary, secondary, and tertiary ASs were defined by comparing their results with the results of antibiotics. RESULTS: Among 16,309 identified studies, 37 were summarized to study the bacteriostasis effects of feed additives, and 89 were included in the meta-analysis and NMA (10,228 pigs). We summarized 268 associations of 57 interventions with 32 bacteria. The order of bacteriostasis effects was as follows: antimicrobial peptides (AMPs) ≈ antibiotics>organic acids>plant extracts>oligosaccharides. We detected associations of 11 feed additives and 11 outcomes. Compared with a basal diet, plant extract, AMPs, probiotics, microelements, organic acids, bacteriophages, lysozyme, zymin, and oligosaccharides significantly improved growth performance (P < 0.05); organic acids, probiotics, microelements, lysozyme, and AMPs remarkably increased the villus height:crypt depth ratio (V/C) (P < 0.05); and plant extracts, zymin, microelements, probiotics, and organic acids notably improved immunity (P < 0.05). The optimal AMP, bacteriophage, lysozyme, microelements, oligosaccharides, organic acids, plants, plant extracts, probiotics, and zymin doses were 0.100%, 0.150%, 0.012%, 0.010%, 0.050%, 0.750%, 0.20%, 0.040%, 0.180%, and 0.100%, respectively. Compared with antibiotics, all investigated feed additives exhibited no significant difference in effects on growth performance, IgG, and diarrhoea index/rate (P > 0.05); AMPs and microelements significantly increased V/C (P < 0.05); and zymin significantly improved lymphocyte levels (P < 0.05). Furthermore, linear weighting sum models were used to comprehensively estimate the overall impact of each feed additive on pig growth and health. CONCLUSIONS: Our findings suggest that AMPs and plant extracts can be used as primary ASs for weaned piglets and growing pigs, respectively. Bacteriophages, zymin, plants, probiotics, oligosaccharides, lysozyme, and microelements can be regarded as secondary ASs. Nucleotides and organic acids can be considered as tertiary ASs. Future studies should further assess the alternative effects of combinational feed additives.