Florfenicol Enhances Colonization of Salmonella enterica serovar Enteritidis floR mutant with Major Alterations to the Intestinal Microbiota and Metabolome in Neonatal Chickens

Author(s):  
Xueran Mei ◽  
Boheng Ma ◽  
Xiwen Zhai ◽  
Anyun Zhang ◽  
Changwei Lei ◽  
...  

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 the intestinal colonization resistance and increasing the susceptibility to Salmonella infection. In this study, we determined the effect of florfenicol (30 mg/kg) on gut colonization of neonatal chickens challenged with Salmonella enterica subsp. enterica serovar Enteritidis ( S. Enteritidis ). We then analyzed the microbial community structure and metabolic profiling of cecal contents using microbial 16S amplicon sequencing and LC-MS untargeted metabolomics, respectively. We also screened the marker metabolites using a multi-omics technique and assessed the effect of these markers on the intestinal colonization 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 the cecal colony structures, with reduced the abundance of Lactobacillus and Bacteroidetes , and increased the 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, 12,13-EpOME and 12,13-diHOME) was most prominently detected. We screened conjugated linoleic acid (CLA) and 12,13-diHOME as the 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 the 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.

2020 ◽  
Author(s):  
Xueran Mei ◽  
Boheng Ma ◽  
Xiwen Zhai ◽  
Anyun Zhang ◽  
Changwei Lei ◽  
...  

Abstract Background: Antimicrobial agents have been widely used in animal farms to prevent and treat animal diseases. However, antimicrobial agents may change the bacterial community and increase susceptibility to the pathogenic bacteria infection. Here, we used metagenomic and metabonomic approach to investigate the effects of florfenicol (FFC) pre-treatment on colonization of Salmonella enterica serovar Enteritidis (S. Enteritidis) in intestines of neonatal chicks through analysis of host responses, microbiota and metabolic changes. Results: We observed that FFC pre-treatment significantly increases the level of S. Enteritidis in the cecal contents, spleen and liver and also induces changes to the cecal microbiota and metabolism. Prior to S. Enteritidis infection, FFC significantly reduced the content of Lactobacillus, and significantly affected the linoleic acid metabolism pathway, including significantly reducing the levels of conjugated linoleic acid (CLA), and significantly increasing the abundance of 12,13-EpOME and 12,13-diHOME in cecum. After infection with S. Enteritidis, the abundance of Proteobacteria were significantly increased and the Salmonella-induced intestinal inflammatory responses and intestinal barrier damage were exacerbated. Supplementation with CLA could maintain intestinal integrity, reduce intestinal inflammation, and directly inhibit Salmonella growth to effectively reduce the Salmonella colonization, whereas the 12,13-diHOME through promoting intestinal inflammation and destroying the intestinal barrier function to support the Salmonella infection. Conclusions: Overall, FFC can decrease levels of Lactobacillus and CLA, and elevate cecal 12,13-diHOME concentrations in neonatal chicks and thereby increases susceptibility to Salmonella infection. This study revealed a potential health impact of antibiotics and disturbed gut microbiota and linoleic acid metabolism might be an intestinal health-impairing attribute and may contribute to Salmonella colonization.


2020 ◽  
Author(s):  
Xueran Mei ◽  
Boheng Ma ◽  
Xiwen Zhai ◽  
Anyun Zhang ◽  
Changwei Lei ◽  
...  

Abstract Background: Antibiotics are widely employed in animal husbandry to prevent and treat diseases. Increasing evidence suggests they may alter the animals’ natural microbiota and increase their susceptibility to pathogen. However, the mechanisms linking the gut microbiota and pathogen colonization in poultry have not yet been full elucidated. Herein, we used metagenomic and metabonomic approaches to investigate the effects of florfenicol (FFC) pre-treatment on Salmonella enterica serovar Enteritidis (S. Enteritidis) colonization in the intestines of neonatal chicks in terms of host response, microbiota composition and metabolism. Results: We determined that FFC pre-treatment significantly alters the cecal microbiota and metabolome, and also increases the intestinal permeability and promotes a pro-inflammatory gene expression profile in the host. Host physiological changes were concordant with significantly increased susceptibility to S. Enteritidis infection in chicks with FFC pre-treatment relative to without pre-treatment chicks. Prior to Salmonella infection, FFC pre-treatment significantly reduced the abundance of Lactobacillus, and significantly affected linoleic acid metabolism, including significantly reducing the levels of conjugated linoleic acid (CLA), and significantly elevating the abundance of 12,13-EpOME and 12,13-diHOME in cecum. After infection with S. Enteritidis, the abundance of Proteobacteria were significantly increased and host inflammatory responses and intestinal permeability were significantly aggravated relative to without FFC pre-treatment chicks, suggestive of a profound exacerbating of the host response influenced by infection in the context of FFC pre-treatment. The linoleic acid metabolism was still significantly different pathway after Salmonella infection, and we screened CLA and 12,13-diHOME as the target metabolites using a multi-omics technique. 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 the intestinal barrier function to sustain Salmonella infection. Therefore, florfenicol reduces production of CLA by inhibiting Lactobacillus growth, increases 12,13-diHOME level of intestine, thereby reducing colonization resistance of neonatal chicks to Salmonella infection.Conclusion: This study reveals the potential health impact of antibiotics on gut microbiota and linoleic acid metabolism and contributing factors influencing Salmonella colonization in neonatal chicks, and provides mechanistic understanding into the role of the antibiotics promote the colonization of pathogens.


2000 ◽  
Vol 79 (6) ◽  
pp. 817-821 ◽  
Author(s):  
M.A. Latour ◽  
A.A. Devitt ◽  
R.A. Meunier ◽  
J.J. Stewart ◽  
B.A. Watkins

2021 ◽  
Vol 12 ◽  
Author(s):  
Huanfang Liu ◽  
Honghua Yang ◽  
Tong Zhao ◽  
Canjia Lin ◽  
Yongqing Li ◽  
...  

Ginger (Zingiber officinale Roscoe) is known for its unique pungent taste and useability in traditional Chinese medicine. The main compounds in ginger rhizome can be classified as gingerols, diarylheptanoids, and volatile oils. The composition and concentrations of the bioactive compounds in ginger rhizome might vary according to the age of the rhizome. In this regard, the knowledge on the transcriptomic signatures and accumulation of metabolites in young (Y), mature (M), and old (O) ginger rhizomes is scarce. This study used HiSeq Illumina Sequencing and UPLC-MS/MS analyses to delineate how the expression of key genes changes in Y, M, and O ginger rhizome tissues and how it affects the accumulation of metabolites in key pathways. The transcriptome sequencing identified 238,157 genes of which 13,976, 11,243, and 24,498 were differentially expressed (DEGs) in Y vs. M, M vs. O, and Y vs. O, respectively. These DEGs were significantly enriched in stilbenoid, diarylheptanoid, and gingerol biosynthesis, phenylpropanoid biosynthesis, plant-hormone signal transduction, starch and sucrose metabolism, linoleic acid metabolism, and α-linoleic acid metabolism pathways. The metabolome profiling identified 661 metabolites of which 311, 386, and 296 metabolites were differentially accumulated in Y vs. M, Y vs. O, and M vs. O, respectively. These metabolites were also enriched in the pathways mentioned above. The DEGs and DAMs enrichment showed that the gingerol content is higher in Y rhizome, whereas the Y, M, and O tissues differ in linoleic and α-linoleic acid accumulation. Similarly, the starch and sucrose metabolism pathway is variably regulated in Y, M, and O rhizome tissues. Our results showed that ginger rhizome growth slows down (Y > M > O) probably due to changes in phytohormone signaling. Young ginger rhizome is the most transcriptionally and metabolically active tissue as compared to M and O. The transitioning from Y to M and O affects the gingerol, sugars, linoleic acid, and α-linoleic acid concentrations and related gene expressions.


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