Antibiotic growth promoters are widely used to improve weight gain. However, misuse of antibiotics can have many negative effects on people. The development of alternatives to antibiotics is an urgent need for livestock production. The aim of this study was to investigate the effects of feed additives as potential antibiotic substitutes (ASs) on bacterial inhibition, growth performance, gut morphology and immunity through meta-analysis (meta-analysis) and network meta-analysis (NMA). In addition, primary, secondary and tertiary ASs were identified by comparing the results with those of antibiotics.

Results
Of the 16,309 studies identified, 37 studies of the bacterial inhibition effect as feed additives were summarized 89 pigs were included in the meta-analysis and NMA (10,228 pigs). We summarized the 268 associations of 57 interventions with 32 bacterial species. The bacterial inhibition effects were ranked as follows: antimicrobial peptides (AMPs) ≈ antibiotics > organic acids > plant extracts > oligosaccharides. We tested 11 feed additives and 11 outcomes for correlation. Compared to basal rations, plant extracts, antimicrobial peptides, probiotics, trace elements, organic acids, phages, lysozyme, enzymes and oligosaccharides significantly improved growth performance (P < 0.05); organic acids, probiotics, trace elements, lysozyme and antimicrobial peptides significantly improved villus height and crypt depth ratio (V/C) (P < 0.05); plant extracts, enzymes, trace elements, probiotics Plant extracts, enzymes, trace elements, probiotics and organic acids significantly improved immune function (P < 0.05). Optimal AMP, phage, lysozyme, trace elements, oligosaccharides, organic acids, plants, plant extracts, probiotics and enzymes were added at 0.100%, 0.150%, 0.012%, 0.010%, 0.050%, 0.750%, 0.20%, 0.040%, 0.180% and 0.100%, respectively. Compared to antibiotics, each feed additive had no significant effect on piglet growth performance, IgG and diarrhea index/rate (P > 0.05); AMPs and trace elements significantly increased V/C (P < 0.05); and enzyme preparations significantly increased lymphocyte levels (P < 0.05). In addition, a linear weighted summation model was used to comprehensively assess the overall effect of each feed additive on pig growth and health.
Conclusion
Our findings suggest that antimicrobial peptides and plant extracts can be used as major antibiotic substitutes (ASs) for weaned piglets and growing pigs. Phages, enzymes, plants, probiotics, oligosaccharides, lysozyme and trace elements can be used as secondary ASs. nucleotides and organic acids can be considered as third ranking Ass. future studies should further evaluate the substitution effect of combined feed additives.


