Florfenicol Enhances Colonization of a Salmonella enterica Serovar Enteritidis floR Mutant with Major Alterations to the Intestinal Microbiota and Metabolome in Neonatal Chickens
Florfenicol Enhances Colonization of a Salmonella enterica Serovar Enteritidis floR Mutant with Major Alterations to the Intestinal Microbiota and Metabolome in Neonatal Chickens
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DOI：
10.1128/aem.01681-21
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发表时间：
2021-12-01
影响因子：
4.4
通讯作者：
Wang, Hongning
中科院分区：
文献类型：
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作者：
Mei, Xueran;Ma, Boheng;Wang, Hongning
氟苯尼考是一种重要的抗生素，常用于家禽生产中预防和治疗沙门氏菌感染。然而，口服氟苯尼考可能会改变动物的天然微生物群和代谢组，从而降低肠道定植抗性并增加对沙门氏菌感染的易感性。在这项研究中，我们确定了氟苯尼考（30 mg/kg体重）对肠道沙门氏菌肠道亚种挑战的新生鸡肠道定植的影响。肠道血清型然后，我们分析了微生物群落结构和盲肠内容物的代谢谱，分别使用微生物16 S扩增子测序和液相色谱-质谱（LC-MS）非靶向代谢组学。我们还使用多组学技术筛选了标记代谢物，并评估了这些标记物对肠道定植的影响。肠道。氟苯尼考给药显著增加了S.盲肠内容物、脾脏和肝脏中的肠毒素，并延长了S.肠道。此外，氟苯尼考显著影响盲肠菌落结构，乳酸杆菌和拟杆菌的丰度降低，梭菌属、梭菌属和Dorea的水平升高。氟苯尼考给药极大地影响了代谢组，最显著地检测到与亚油酸代谢（亚油酸、共轭亚油酸[CLA]、12，13-EpOME和12，13-diHOME）相关的代谢途径的扰动。我们筛选了CLA和12，13-diHOME作为标记代谢物，其与乳杆菌属、梭菌属和Dorea高度相关。补充CLA可维持肠道完整性，减少肠道炎症，加速肠道沙门氏菌清除和肠病缓解，而12，13-diHOME治疗可促进肠道炎症，破坏肠道屏障功能以维持沙门氏菌感染。因此，这些结果突出表明，氟苯尼考改变肠道菌群和代谢的新生鸡，促进沙门氏菌感染，主要是通过影响亚油酸的代谢。重要氟苯尼考是一种广谱的氟衍生物的氯霉素经常用于家禽，以防止/治疗沙门氏菌。然而，口服氟苯尼考可能导致鸡肠道微生物群和代谢组的改变，从而降低对沙门氏菌感染的定植抗性，并且尚未完全阐明抗生素与家禽中沙门氏菌定植之间的可能机制。在目前的研究中，我们表明，增加殖民的S。氟苯尼考给药鸡的肠道炎与肠道微生物群和代谢谱的大幅变化相关。最有影响力的亚油酸代谢与肠道中乳酸杆菌、梭菌和Dorea的丰度高度相关。筛选出的亚油酸代谢中的靶代谢产物对S.肠道细菌定植、肠道炎症和肠道屏障功能。我们的研究结果提供了一个更好的了解抗生素干预后动物物种对沙门氏菌的易感性，这可能有助于阐明对动物和人类健康都很重要的感染机制。
Florfenicol is an important antibiotic commonly used in poultry production to prevent and treat Salmonella infection. However, oral administration of florfenicol may alter the animals' natural microbiota and metabolome, thereby reducing intestinal colonization resistance and increasing susceptibility to Salmonella infection. In this study, we determined the effect of florfenicol (30 mg/kg of body weight) on gut colonization of neonatal chickens challenged with Salmonella enterica subsp. enterica serovar Enteritidis. We then analyzed the microbial community structure and metabolic profiles of cecal contents using microbial 16S amplicon sequencing and liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics, respectively. We also screened the marker metabolites using a multi-omics technique and assessed the effect of these markers on intestinal colonization by S. Enteritidis. Florfenicol administration significantly increased the loads of S. Enteritidis in cecal contents, spleen, and liver and prolonged the residence of S. Enteritidis. Moreover, florfenicol significantly affected cecal colony structures, with reduced abundances of Lactobacillus and Bacteroidetes and increased levels of Clostridia, Clostridium, and Dorea. The metabolome was greatly influenced by florfenicol administration, and perturbation in metabolic pathways related to linoleic acid metabolism (linoleic acid, conjugated linoleic acid [CLA], 12,13-EpOME, and 12,13-diHOME) was most prominently detected. We screened CLA and 12,13-diHOME as marker metabolites, which were highly associated with Lactobacillus, Clostridium, and Dorea. Supplementation with CLA maintained intestinal integrity, reduced intestinal inflammation, and accelerated Salmonella clearance from the gut and remission of enteropathy, whereas treatment with 12,13-diHOME promoted intestinal inflammation and disrupted intestinal barrier function to sustain Salmonella infection. Thus, these results highlight that florfenicol alters the intestinal microbiota and metabolism of neonatal chickens and promotes Salmonella infection mainly by affecting linoleic acid metabolism.IMPORTANCE Florfenicol is a broad-spectrum fluorine derivative of chloramphenicol frequently used in poultry to prevent/treat Salmonella. However, oral administration of florfenicol may lead to alterations in the microbiota and metabolome in the chicken intestine, thereby reducing colonization resistance to Salmonella infection, and the possible mechanisms linking antibiotics and Salmonella colonization in poultry have not yet been fully elucidated. In the current study, we show that increased colonization by S. Enteritidis in chickens administered florfenicol is associated with large shifts in the gut microbiota and metabolic profiles. The most influential linoleic acid metabolism is highly associated with the abundances of Lactobacillus, Clostridium, and Dorea in the intestine. The screened target metabolites in linoleic acid metabolism affect S. Enteritidis colonization, intestinal inflammation, and intestinal barrier function. Our findings provide a better understanding of the susceptibility of animal species to Salmonella after antibiotic intervention, which may help to elucidate infection mechanisms that are important for both animal and human health.