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. 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. 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.

中文翻译：

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猪用抗生素替代品的总体评估：一组荟萃分析

抗生素生长促进剂被广泛用于改善体重增加。但是，滥用抗生素会对人们产生许多负面影响。在牲畜生产中迫切需要开发抗生素替代品。我们旨在进行荟萃分析和网络荟萃分析（NMA），以研究饲料添加剂作为潜在的抗生素替代品（ASs）对抑菌，生长性能，肠道形态和免疫力的影响。此外，通过将它们的结果与抗生素的结果进行比较来定义一级，二级和三级AS。在16309项确定的研究中，总结了37项用于研究饲料添加剂的抑菌作用，荟萃分析和NMA纳入了89篇（10228头猪）。我们总结了57种干预措施与32种细菌的268个关联。抑菌作用的顺序如下：抗菌肽（AMPs）≈抗生素>有机酸>植物提取物>寡糖。我们检测到11种饲料添加剂与11种结果的关联。与基础饮食相比，植物提取物，AMP，益生菌，微量元素，有机酸，噬菌体，溶菌酶，酵素和寡糖显着改善了生长性能（P <0.05）；有机酸，益生菌，微量元素，溶菌酶和AMP显着增加了绒毛高度：隐窝深度比（V / C）（P <0.05）；以及植物提取物，酵素，微量元素，益生菌和有机酸可显着提高免疫力（P <0.05）。最佳AMP，噬菌体，溶菌酶，微量元素，低聚糖，有机酸，植物，植物提取物，益生菌和zymin的剂量分别为0.100％，0.150％，0.012％，0.010％，0.050％，0。分别为750％，0.20％，0.040％，0.180％和0.100％。与抗生素相比，所有研究的饲料添加剂对生长性能，IgG和腹泻指数/速率的影响均无显着差异（P> 0.05）；AMP和微量元素显着提高了V / C（P <0.05）；zymin显着改善了淋巴细胞水平（P <0.05）。此外，线性加权总和模型用于全面评估每种饲料添加剂对猪生长和健康的总体影响。我们的发现表明，AMPs和植物提取物可以分别用作断奶仔猪和生长猪的主要AS。噬菌体，酶，植物，益生菌，寡糖，溶菌酶和微量元素可以被认为是继发性AS。核苷酸和有机酸可以被认为是三级自治系统。