Directly Coupled High-Performance Liquid Chromatography and Nuclear Magnetic Resonance Spectroscopic with Chemometric Studies on Metabolic Variation in Sprague–Dawley Rats

Gavaghan, Claire L.; Nicholson, Jeremy K.; Connor, Susan C.; Wilson, Ian D.; Wright, Brian; Holmes, Elaine

doi:10.1006/abio.2000.5034

Cited by 77 publications

(56 citation statements)

References 18 publications

(17 reference statements)

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“…Microbial metabolism resulting in potentiated clinical effect [34,35] intricate system consisting of a microbial and a human component. However, in many cases the process, biochemical pathway, or specific reaction remains unknown, which renders the analysis of those interactions by reductionist approaches difficult.…”

Section: Carcinogenic Agentsmentioning

confidence: 99%

Diet-Microbiota Interactions and their Implications for Healthy Living

2014

Health and the Gut

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The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP) opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics), notably in the human gut. The HMP continues to characterize the microbial communities associated with the human gut, determine whether there is a common gut microbiome profile shared among healthy humans, and investigate the effect of its alterations on health. Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. We discuss a few examples representing how the microbiome interacts with human metabolic enzymes in the liver and intestine. In addition, we attempt to envisage a roadmap for the future implications of the HMP on therapeutics and personalized medicine.

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Section: Carcinogenic Agentsmentioning

confidence: 99%

Diet-Microbiota Interactions and their Implications for Healthy Living

2014

Health and the Gut

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“…53 For instance, urinary excretion of calcium in the rat is dependent on food consumption. 105 Plasma profiles are also dietary-related, for example plasma phosphate and calcium concentrations in the rat are effected by food intake. 99 Phipps and co-workers have shown that dietary changes in the rat alter the amount of hippurate and chlorogenic acid metabolites such as m-hydroxyphenylpropionic acid excreted in the urine.…”

Section: Metabonomic Studies Of Physiological Variationmentioning

confidence: 99%

“…In a more recent study, 105 statistical analysis of a large homologous population of SD rats fed on a standard rat diet, where all batches were within the manufacturer's specification, identified two sub-populations of rat in the first two PCs [ Fig. 11(a)].…”

Section: Metabonomic Studies Of Physiological Variationmentioning

confidence: 99%

NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition

et al. 2004

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Strategies such as genomics, proteomics and metabonomics are being applied with increasing frequency in the pharmaceutical industry. For each of these approaches, toxicological response can be measured by terms of deviation from control or baseline status. However, in order to accurately define drug-induced response, it is necessary to characterize the normal degree of physiological variation in the absence of stimuli. Here, 1 H NMR spectroscopic-based analyses of the metabolic composition of urine in experimental animals under various normal physiological conditions are reviewed. In particular, the effects of inter-animal and diurnal variation, gender, age, diet, species, strain, hormonal status and stress on the biochemical composition of urine are explored. Pattern recognition methods facilitate the comparison of urine NMR spectra over a given time-course, enabling the establishment of changes in profile and highlighting the dynamic metabolic status of an organism. Thus metabonomic approaches based on information-rich spectroscopic data sets can be used to evaluate normal physiological variation and for investigation of drug safety issues.

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“…The HIP rats represent the conventional metabonomic phenotype for Sprague-Dawley rats typically determined in our laboratory. Literature reports (13,14) and a cohabitation experiment (1) suggested that the difference in the two phenotypes was due to differing gut flora populations between CA and HIP rats.…”

Section: Introductionmentioning

confidence: 99%

Metabonomic Evaluation of Schaedler Altered Microflora Rats

Rohde

Wells

Robosky

et al. 2007

Chem. Res. Toxicol.

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Previously, we identified two distinct metabonomic phenotypes in Sprague-Dawley rats sourced from two different rooms (colonies) in the Charles River, Raleigh facility [Robosky, L. C., Wells, D. F., Egnash, L. A., Manning, M. L., Reily, M. D., and Robertson, D. G. (2005) Metabonomic identification of two distinct phenotypes in Sprague-Dawley (Crl:CD(SD)) rats. Toxicol. Sci. 87,[277][278][279][280][281][282][283][284]. On the basis of literature reports and cohabitation experiments, we concluded that the differing phenotypes were due to different gut flora populations. One hypothesis explaining this phenomenon was attributed to the practice of initiating new colonies with rats derived from foundation colonies that had limited gut floral populations, the Charles River altered Schaedler flora (CRASF) rats. We hypothesized that the lack of differentiation of CRASF rats to the full complement of microflora was responsible for the altered phenotype characterized by increased urinary chlorogenic acid metabolites and decreased hippurate (CA rats) as opposed to the prevalent phenotype characterized by the inverse ratio of these metabolites (HIP rats). Upon receipt, it was confirmed that the CRASF rats exhibited a metabonomic profile similar to CA rats that remained constant while animals were housed individually in a dedicated animal room. However, exposure of CRASF rats to HIP rats, or their bedding, led to a relatively rapid but variable rate of reversion to the historic HIP type metabolic profile. On the basis of the results, we conclude that CRASF rats have a unique metabolic profile due to their limited gut flora constitution. If rigorous isolation procedures are not employed, the CRASF phenotype will eventually differentiate into the more typical HIP phenotype with a time course that may be quite variable. Given the marked metabolic heterogeneity between the phenotypes, this work highlights the importance of monitoring rat metabolic profiles.

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Directly Coupled High-Performance Liquid Chromatography and Nuclear Magnetic Resonance Spectroscopic with Chemometric Studies on Metabolic Variation in Sprague–Dawley Rats

Cited by 77 publications

References 18 publications

Diet-Microbiota Interactions and their Implications for Healthy Living

Diet-Microbiota Interactions and their Implications for Healthy Living

NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition

Metabonomic Evaluation of Schaedler Altered Microflora Rats

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