Dataset Information

The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome.

ABSTRACT: Carbadox is a quinoxaline-di-N-oxide antibiotic fed to over 40% of young pigs in the United States that has been shown to induce phage DNA transduction in vitro; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the in vivo longitudinal effects of carbadox on swine gut microbial gene expression (fecal metatranscriptome) and phage population dynamics (fecal dsDNA viromes). Microbial metagenome, transcriptome, and virome sequences were annotated for taxonomic inference and gene function by using FIGfam (isofunctional homolog sequences) and SEED subsystems databases. When the beta diversities of microbial FIGfam annotations were compared, the control and carbadox communities were distinct 2 days after carbadox introduction. This effect was driven by carbadox-associated lower expression of FIGfams (n = 66) related to microbial respiration, carbohydrate utilization, and RNA metabolism (q < 0.1), suggesting bacteriostatic or bactericidal effects within certain populations. Interestingly, carbadox treatment caused greater expression of FIGfams related to all stages of the phage lytic cycle 2 days following the introduction of carbadox (q ?0.07), suggesting the carbadox-mediated induction of prophages and phage DNA recombination. These effects were diminished by 7 days of continuous carbadox in the feed, suggesting an acute impact. Additionally, the viromes included a few genes that encoded resistance to tetracycline, aminoglycoside, and beta-lactam antibiotics but these did not change in frequency over time or with treatment. The results show decreased bacterial growth and metabolism, prophage induction, and potential transduction of bacterial fitness genes in swine gut bacterial communities as a result of carbadox administration.IMPORTANCE FDA regulations on agricultural antibiotic use have focused on antibiotics that are important for human medicine. Carbadox is an antibiotic not used in humans but frequently used on U.S. pig farms. It is important to study possible side effects of carbadox use because it has been shown to promote bacterial evolution, which could indirectly impact antibiotic resistance in bacteria of clinical importance. Interestingly, the present study shows greater prophage gene expression in feces from carbadox-fed animals than in feces from nonmedicated animals 2 days after the initiation of in-feed carbadox treatment. Importantly, the phage genetic material isolated in this study contained genes that could provide resistance to antibiotics that are important in human medicine, indicating that human-relevant antibiotic resistance genes are mobile between bacteria via phages. This study highlights the collateral effects of antibiotics and demonstrates the need to consider diverse antibiotic effects whenever antibiotics are being used or new regulations are considered.

SUBMITTER: Johnson TA

PROVIDER: S-EPMC5550749 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome.

Johnson Timothy A TA Looft Torey T Severin Andrew J AJ Bayles Darrell O DO Nasko Daniel J DJ Wommack K Eric KE Howe Adina A Allen Heather K HK

mBio 20170808 4

Carbadox is a quinoxaline-di-N-oxide antibiotic fed to over 40% of young pigs in the United States that has been shown to induce phage DNA transduction in vitro; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the in vivo longitudinal effects of carbadox on swine gut microbial gene expression (fecal metatranscriptome) and phage population dynamics (fecal dsDNA viromes). Microbial metagenome, transcriptome, and virome sequ ...[more]

PMID: 28790203

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Project description:BackgroundFeed efficiency is a crucial parameter in swine production, given both its economic and environmental impact. The gut microbiota plays an essential role in nutrient digestibility and is, therefore, likely to affect feed efficiency. This study aimed to characterize feed efficiency, fatness traits, and gut microbiome composition in three major breeds of domesticated swine and investigate a possible link between feed efficiency and gut microbiota composition.ResultsAverage daily feed intake (ADFI), average daily gain (ADG), feed conversion ratio (FCR), residual feed intake (RFI), backfat, loin depth, and intramuscular fat of 615 pigs belonging to the Duroc (DR), Landrace (LR), and Large White (LW) breeds were measured. Gut microbiota composition was characterized by 16S rRNA gene sequencing. Orthogonal contrasts between paternal line (DR) and maternal lines (LR+LW) and between the two maternal lines (LR versus LW) were performed. Average daily feed intake and ADG were statistically different with DR having lower ADFI and ADG compared to LR and LW. Landrace and LW had a similar ADG and RFI, with higher ADFI and FCR for LW. Alpha diversity was higher in the fecal microbial communities of LR pigs than in those of DR and LW pigs for all time points considered. Duroc communities had significantly higher proportional representation of the Catenibacterium and Clostridium genera compared to LR and LW, while LR pigs had significantly higher proportions of Bacteroides than LW for all time points considered. Amplicon sequence variants from multiple genera (including Anaerovibrio, Bacteroides, Blautia, Clostridium, Dorea, Eubacterium, Faecalibacterium, Lactobacillus, Oscillibacter, and Ruminococcus) were found to be significantly associated with feed efficiency, regardless of the time point considered.ConclusionsIn this study, we characterized differences in the composition of the fecal microbiota of three commercially relevant breeds of swine, both over time and between breeds. Correlations between different microbiome compositions and feed efficiency were established. This suggests that the microbial community may contribute to shaping host productive parameters. Moreover, our study provides important insights into how the intestinal microbial community might influence host energy harvesting capacity. A deeper understanding of this process may allow us to modulate the gut microbiome in order to raise more efficient animals. Video Abstract.

Project description:Antibiotics are used in livestock and poultry production to treat and prevent disease as well as to promote animal growth. Carbadox is an in-feed antibiotic that is widely used in swine production to prevent dysentery and to improve feed efficiency. The goal of this study was to characterize the effects of carbadox and its withdrawal on the swine gut microbiota. Six pigs (initially 3-weeks old) received feed containing carbadox and six received unamended feed. After 3-weeks of continuous carbadox administration, all pigs were switched to a maintenance diet without carbadox. DNA was extracted from feces (n = 142) taken before, during, and following (6-week withdrawal) carbadox treatment. Phylotype analysis using 16S rRNA sequences showed the gradual development of the non-medicated swine gut microbiota over the 8-week study, and that the carbadox-treated pigs had significant differences in bacterial membership relative to non-medicated pigs. Enumeration of fecal Escherichia coli showed that a diet change concurrent with carbadox withdrawal was associated with an increase in the E. coli in the non-medicated pigs, suggesting that carbadox pre-treatment prevented an increase of E. coli populations. In-feed carbadox caused striking effects within 4 days of administration, with significant alterations in both community structure and bacterial membership, notably a large relative increase in Prevotella populations in medicated pigs. Digital PCR was used to show that the absolute abundance of Prevotella was unchanged between the medicated and non-medicated pigs despite the relative increase shown in the phylotype analysis. Carbadox therefore caused a decrease in the abundance of other gut bacteria but did not affect the absolute abundance of Prevotella. The pending regulation on antibiotics used in animal production underscores the importance of understanding how they modulate the microbiota and impact animal health, which will inform the search for antibiotic alternatives.

Project description:Diet is a major determinant of intestinal microbiome composition. While studies have evaluated microbiome responses to diet variation, less is understood about how the act of feeding influences the microbiome, independent of diet type. Here, we use the clownfish Premnas biaculeatus, a species reared commonly in ornamental marine aquaculture, to test how the diversity, predicted gene content, and gene transcription of the microbiome vary over a 2-day diurnal period with a single daily feeding event. This study used fish fed four times daily, once daily, or every 3 days prior to the diurnal period, allowing us also to test how feeding frequency affected microbiome diversity. The amount of time between feedings had no effect on baseline diversity of the microbiome. In contrast, the act of feeding itself caused a significant short-term change in the microbiome, with microbiome diversity, predicted gene content, and gene transcription varying significantly between time points immediately before and 1.5?hours postfeeding. Variation was driven by abundance shifts involving exact sequence variants (ESVs), with one ESV identified as Photobacterium sp. increasing from <0.5% of sequences immediately prefeeding to 34% at 1.5?h postfeeding. Other ESVs from a range of microbial groups also increased dramatically after feeding, with the majority also detected in the food. One ESV identified as Clostridium perfringens represented up to 55% of sequences but did not vary significantly over the diurnal period and was not detected in the food. Postfeeding samples were enriched in transcripts and predicted genes for social interactions, cell motility, and coping with foreign DNA, whereas time points farther from feeding were enriched in genes of diverse catabolic and biosynthetic functions. These results confirm feeding as a significant destabilizing force in clownfish intestinal microbiomes, likely due to both input of cells attached to food and stimulation of resident microbes. Microbes such as Photobacterium may episodically transition from environmental reservoirs to growth in the gut, likely in association with food particles. This transition may be facilitated by functions for navigating a new environment and interacting with neighboring microbes and host cells. Other taxa, such as Clostridium, are comparatively stable intestinal members and less likely to be affected by passing food. Conclusions about microbiome ecology may therefore differ based on when samples were collected relative to the last feeding.IMPORTANCE Despite extensive study of intestinal microbiome diversity and the role of diet type in structuring gut microbial communities, we know very little about short-term changes in the intestinal microbiome as a result of feeding alone. Sampling microbiomes over a feeding cycle will allow us to differentiate opportunistic, feeding-responsive microbes from resident, potentially commensal members of the gut community. Also, since feeding has the potential to alter microbiome structure, sampling at different points relative to the last feeding event will likely yield different conclusions about microbiome composition and function. This variation should be addressed in comparative microbiome studies. Our study contributes to knowledge of short-term changes in the gut microbiome associated with feeding events.

Dataset Information

The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome.

Publications

The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome.

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