摘要
      抗生素耐药性病原体的日益流行使人们更好地了解了导致这种扩张的潜在过程。集约化养猪场被认为是抗生素抗性基因（ARG）传播的热点之一。噬菌体作为ARGs的重要移动载体，广泛存在于动物肠道中。然而，我们对猪肠道中噬菌体相关ARGs及其潜在驱动因素的了解是有限的。本文分别对健康仔猪和腹泻仔猪不同肠道（回肠、盲肠和粪便）内容物的病毒DNA和总DNA进行了宏基因组测序和分析。我们发现仔猪盲肠中的噬菌体是ARGs和移动遗传元件（MGE）基因的主要储存库。噬菌体相关MGE是影响ARGs维持和转移的重要因素。有趣的是，ARGs和MGE基因在仔猪肠道噬菌体中的共定位似乎不是随机选择的，而是与特定的噬菌体宿主（链球菌）有关。此外，在腹泻仔猪的粪便中，携带ARGs和MGE基因的噬菌体的丰度显著增加，多价噬菌体（宿主范围广的噬菌体）的多样性也显著增加，这将有助于ARGs在细菌群落中的转染和更广泛的分布。此外，腹泻粪便中多价噬菌体的预测宿主谱往往是潜在的肠道致病属，这大大增加了肠道病原体获得ARGs的风险。值得注意的是，我们还在仔猪肠道模仿病毒的序列中发现了ARG同源基因，这表明仔猪肠道模拟病毒是ARG的潜在储存库。总之，本研究极大地扩展了我们对仔猪肠道微生物组的了解，揭示了仔猪肠道ARG维持和传播的潜在机制，并为畜牧业中ARG污染的预防和控制提供了参考。
Abstract
The growing prevalence of antibiotic-resistant pathogens has led to a better understanding of the underlying processes that lead to this expansion. Intensive pig farms are considered one of the hotspots for antibiotic resistance gene (ARG) transmission. Phages, as important mobile carriers of ARGs, are widespread in the animal intestine. However, our understanding of phage-associated ARGs in the pig intestine and their underlying drivers is limited. Here, metagenomic sequencing and analysis of viral DNA and total DNA of different intestinal (ileum, cecum and feces) contents in healthy piglets and piglets with diarrhea were separately conducted. We found that phages in piglet ceca are the main repository for ARGs and mobile genetic element (MGE) genes. Phage-associated MGEs are important factors affecting the maintenance and transfer of ARGs. Interestingly, the colocalization of ARGs and MGE genes in piglet gut phages does not appear to be randomly selected but rather related to a specific phage host (Streptococcus). In addition, in the feces of piglets with diarrhea, the abundance of phages carrying ARGs and MGE genes was significantly increased, as was the diversity of polyvalent phages (phages with broad host ranges), which would facilitate the transfection and wider distribution of ARGs in the bacterial community. Moreover, the predicted host spectrum of polyvalent phages in diarrheal feces tended to be potential enteropathogenic genera, which greatly increased the risk of enteropathogens acquiring ARGs. Notably, we also found ARG-homologous genes in the sequences of piglet intestinal mimiviruses, suggesting that the piglet intestinal mimiviruses are a potential repository of ARGs. In conclusion, this study greatly expands our knowledge of the piglet gut microbiome, revealing the underlying mechanisms of maintenance and dissemination of piglet gut ARGs and providing a reference for the prevention and control of ARG pollution in animal husbandry.

https://www.sciencedirect.com/science/article/abs/pii/S0048969722074046