NMR HRMAS spectroscopy of lung biopsy samples: Comparison study between human, pig, rat, and mouse metabolomics

Benahmed, Malika A.; Elbayed, Karim; Daubeuf, François; Santelmo, Nicola; Frossard, Nelly; Namer, Izzie Jacques

doi:10.1002/mrm.24658

Cited by 23 publications

(18 citation statements)

References 30 publications

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“…variations can be compared (Merrifield et al, 2011;Benahmed et al, 2014). Several studies analysed metabolites in different pig biological systems (tissues or biofluids) to try to capture metabolomic signatures that could explain, at least in part, differences between the tested experimental designs, including different diets, other treatments or environmental factors (e.g.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics evidences plasma and serum biomarkers differentiating two heavy pig breeds

Bovo

Mazzoni

Galimberti

et al. 2016

Animal

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In pigs, many production traits are known to vary among breeds or lines. These traits can be considered end phenotypes or external traits as they are the final results of complex biological interactions and processes whose fine biological mechanisms are still largely unknown. This study was designed to compare plasma and serum metabolomic profiles between animals of two heavy pig breeds (12 Italian Large White and 12 Italian Duroc), testing indirectly the hypothesis that different genetic backgrounds might be the determining factors of differences observed on the level of metabolites in the analyzed biofluids between breeds. We used a targeted metabolomic approach based on mass spectrometric detection of about 180 metabolites and applied a statistical validation pipeline to identify differences in the metabolomic profiles of the two heavy pig breeds. Blood samples were collected after jugulation at the slaughterhouse and prepared for metabolomics analysis that was carried out using the Biocrates AbsoluteIDQ p180 Kit, covering five different biochemical classes: glycerophospholipids, amino acids, biogenic amines, hexoses and acylcarnitines. A statistical pipeline that included the selection of the most relevant metabolites differentiating the two breeds by sparse Partial Least Squares Discriminant Analysis (sPLS-DA) was coupled with a stability test and significance test determined with leave one out and permutation procedures. sPLS-DA plots clearly separated the pigs of the two investigated breeds. A few metabolites (a total of five metabolites considering the two biofluids) involved in key metabolic pathways largely contributed to these differences between breeds. In particular, a higher level of the sphingomyelins SM (OH) C14:1 (both in plasma and serum), SM (OH) C16:1 (in serum) and SM C16:0 (in serum) were observed in Italian Duroc than in Italian Large White pigs and the inverse was for the biogenic amine kynurenine (in plasma). The level of another biogenic amine (acetylornithine) was higher in Italian Large White than in Italian Duroc pigs in both analysed biofluids. These results provided biomarkers that could be important to understand the biological differences between these two heavy pig breeds. In particular, according to the functional role played by sphingomyelins in obesity-induced inflammatory responses, it could be possible to speculate that a higher level of sphingomyelins in Italian Duroc might be related to the higher interrmuscular fat deposition of this breed compared with the Italian Large White. Additional studies will be needed to evaluate the relevance of these biomarkers for practical applications in pig breeding and nutrition.Keywords: pig breeding, metabolites, molecular phenotypes, metabolic pathway, production traits ImplicationsThis study showed that different pig breeds are characterized by different metabolomics profiles. The statistical approach that was adopted identified a few biomarkers whose level in plasma and serum described the differences between two heavy pig breeds. T...

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Section: Discussionmentioning

confidence: 99%

Metabolomics evidences plasma and serum biomarkers differentiating two heavy pig breeds

Bovo

Mazzoni

Galimberti

et al. 2016

Animal

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“…Insect hosts have limited similarity to humans and it is now clear that rodent tissue chemistry (Benahmed et al, 2014) and immune responses (Seok et al, 2013) differ significantly from those of humans. In vivo experiments are also limited in duration (acute or semichronic) due to restrictions imposed by ethical concerns, cost and host response to disease (Wiles et al, 2006;Hoffmann, 2007;Kukavica-Ibrulj & Levesque, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Pigs have lung structure, immunology and chemistry more similar to those of humans than do mice (Meurens et al, 2012;Benahmed et al, 2014) and lung tissue is available as a byproduct from the meat industry; thus, the model poses no ethical concerns. The model is cheap and allows for high levels of replication: several dozen individual pieces of tissue can be dissected from each pair of lungs.…”

Section: Introductionmentioning

confidence: 99%

An ex vivo lung model to study bronchioles infected with Pseudomonas aeruginosa biofilms

Harrison

Diggle

2016

Microbiology

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A key aim in microbiology is to determine the genetic and phenotypic bases of bacterial virulence, persistence and antimicrobial resistance in chronic biofilm infections. This requires tractable, high-throughput models that reflect the physical and chemical environment encountered in specific infection contexts. Such models will increase the predictive power of microbiological experiments and provide platforms for enhanced testing of novel antibacterial or antivirulence therapies. We present an optimized ex vivo model of cystic fibrosis lung infection: ex vivo culture of pig bronchiolar tissue in artificial cystic fibrosis mucus. We focus on the formation of biofilms by Pseudomonas aeruginosa. We show highly repeatable and specific formation of biofilms that resemble clinical biofilms by a commonly studied laboratory strain and ten cystic fibrosis isolates of this key opportunistic pathogen.

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“…This model is useful for several reasons. First, pigs are arguably better models for studying human disease than are rodents or invertebrates (17–19). Second, lungs can be obtained from butchers: since little or no lung tissue is used in food production, lungs are (i) cheap and (ii) a waste product whose use does not raise ethical questions about the slaughter of animals for research.…”

Section: Introductionmentioning

confidence: 99%

Development of an Ex Vivo Porcine Lung Model for Studying Growth, Virulence, and Signaling of Pseudomonas aeruginosa

et al. 2014

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Research into chronic infection by bacterial pathogens, such as Pseudomonas aeruginosa, uses various in vitro and live host models. While these have increased our understanding of pathogen growth, virulence, and evolution, each model has certain limitations. In vitro models cannot recapitulate the complex spatial structure of host organs, while experiments on live hosts are limited in terms of sample size and infection duration for ethical reasons; live mammal models also require specialized facilities which are costly to run. To address this, we have developed an ex vivo pig lung (EVPL) model for quantifying Pseudomonas aeruginosa growth, quorum sensing (QS), virulence factor production, and tissue damage in an environment that mimics a chronically infected cystic fibrosis (CF) lung. In a first test of our model, we show that lasR mutants, which do not respond to 3-oxo-C12-homoserine lactone (HSL)-mediated QS, exhibit reduced virulence factor production in EVPL. We also show that lasR mutants grow as well as or better than a corresponding wild-type strain in EVPL. lasR mutants frequently and repeatedly arise during chronic CF lung infection, but the evolutionary forces governing their appearance and spread are not clear. Our data are not consistent with the hypothesis that lasR mutants act as social “cheats” in the lung; rather, our results support the hypothesis that lasR mutants are more adapted to the lung environment. More generally, this model will facilitate improved studies of microbial disease, especially studies of how cells of the same and different species interact in polymicrobial infections in a spatially structured environment.

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NMR HRMAS spectroscopy of lung biopsy samples: Comparison study between human, pig, rat, and mouse metabolomics

Abstract: Using the metabolomics by NMR high-resolution magic angle spinning spectroscopy on lung biopsy, samples allowed to highlight that pig lung seems to be close to human lung as regarding its metabolite composition with more similarities than dissimilarities.

Cited by 23 publications

References 30 publications

Metabolomics evidences plasma and serum biomarkers differentiating two heavy pig breeds

Metabolomics evidences plasma and serum biomarkers differentiating two heavy pig breeds

An ex vivo lung model to study bronchioles infected with Pseudomonas aeruginosa biofilms

Development of an Ex Vivo Porcine Lung Model for Studying Growth, Virulence, and Signaling of Pseudomonas aeruginosa

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