Table_6_Effects of Dietary Antimicrobial Growth Promoters on Performance Parameters and Abundance and Diversity of Broiler Chicken Gut Microbiome and Selection of Antibiotic Resistance Genes.docx

Antimicrobial growth promoters (AGPs) are commonly used in broiler production. There is a huge societal concern around their use and their contribution to the proliferation of antimicrobial resistance (AMR) in food-producing animals and dissemination to humans or the environment. However, there is a paucity of comprehensive experimental data on their impact on poultry production and the AMR resistome. Here, we investigated the effect of five antimicrobial growth promoters (virginiamycin, chlortetracycline, bacitracin methyl disalicylate, lincomycin, and tylosin) used in the commercial broiler production in the Indian subcontinent and in the different parts of the world for three consecutive production cycles on performance variables and also the impact on gut bacteria, bacteriophage, and resistome profile using culture-independent approaches. There was no significant effect of AGPs on the cumulative growth or feed efficiency parameters at the end of the production cycles and cumulative mortality rates were also similar across groups. Many antibiotic resistance genes (ARGs) were ubiquitous in the chicken gut irrespective of AGP supplementation. In total, 62 ARGs from 15 antimicrobial classes were detected. Supplementation of AGPs influenced the selection of several classes of ARGs; however, this was not correlated necessarily with genes relevant to the AGP drug class; some AGPs favored the selection of ARGs related to antimicrobials not structurally related to the AGP. AGPs did not impact the gut bacterial community structure, including alpha or beta diversity significantly, with only 16–20 operational taxonomic units (OTUs) of bacteria being altered significantly. However, several AGPs significantly reduced the population density of some of the potential pathogenic genera of bacteria, such as Escherichia coli. Chlortetracycline increased the abundance of Escherichia phage, whereas other AGPs did not influence the abundance of bacteriophage significantly. Considering the evidence that AGPs used in poultry production can select for resistance to more than one class of antimicrobial resistance, and the fact that their effect on performance is not significant, their use needs to be reduced and there is a need to monitor the spread of ARGs in broiler chicken farms.

抗菌生长促进剂（Antimicrobial growth promoters, AGPs）是肉鸡养殖中的常用添加剂。当前，其在养殖中的应用及其导致食用动物体内抗菌耐药性（Antimicrobial resistance, AMR）扩散、并进一步传播至人类或环境的问题，已引发广泛的社会关切。然而，目前针对AGPs对家禽养殖生产及耐药组（resistome）的影响，仍缺乏全面的实验研究数据。本研究针对南亚次大陆及全球多地商业化肉鸡养殖中常用的五种抗菌生长促进剂——维吉尼亚霉素、金霉素、杆菌肽甲基二水杨酸酯、林可霉素与泰乐菌素——开展了连续三轮养殖周期的试验，探究其对生产性能指标的影响，并通过非培养依赖（culture-independent）研究方法，分析其对肠道菌群、噬菌体及耐药组特征的作用。试验结果表明，养殖周期结束时，AGPs对肉鸡的累积生长性能或饲料效率参数无显著影响，各组的累积死亡率也无明显差异。无论是否添加AGPs，多种抗生素耐药基因（Antibiotic resistance genes, ARGs）在鸡肠道内均广泛存在。本研究共检测到来自15类抗菌药物的62种ARGs。AGPs的添加会对部分类别的ARGs筛选产生影响，但这种影响未必与对应AGPs所属药物类别的耐药基因相关；部分AGPs甚至会促进与自身结构无关的抗菌药物相关ARGs的富集。AGPs对肠道细菌群落结构（包括α多样性与β多样性）无显著影响，仅16~20个细菌操作分类单元（operational taxonomic units, OTUs）发生了显著改变。不过，部分AGPs可显著降低部分潜在致病细菌属的种群密度，例如大肠埃希氏菌（Escherichia coli）。金霉素可提升大肠埃希氏菌噬菌体的丰度，而其余AGPs对噬菌体丰度无显著影响。综合上述研究结果，肉鸡养殖中使用的AGPs可促使对多类别抗菌药物的耐药性产生，且其对生产性能并无显著提升作用，因此应当减少AGPs的使用，并加强对肉鸡养殖场ARGs传播情况的监测。