The promise of metabolic phenotyping in gastroenterology and hepatology

Holmes, Elaine; Wijeyesekera, Anisha; Taylor-Robinson, Simon D; Nicholson, Jeremy K.

doi:10.1038/nrgastro.2015.114

Cited by 70 publications

(43 citation statements)

References 153 publications

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“…The in vitro MRS technique on body fluid samples has a role both in large-scale population-based screening without specific a priori hypotheses and in demonstrating the response of the individual to therapy. 48 At clinical magnetic field strengths, whole body in vivo MRS has provided insight into pathogenic mechanisms of cell turnover in cirrhosis, [49][50][51] the process of allograft rejection following liver transplantation, 52 changes in cognitive function, osmolyte concentrations and low-grade cerebral oedema in hepatic encephalopathy and the mechanisms underlying fatigue in primary biliary cirrhosis. 53,54 …”

Section: Applicationsmentioning

confidence: 99%

Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians

Tognarelli

Dawood

Shariff

et al. 2015

Journal of Clinical and Experimental Hepatology

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Magnetic resonance spectroscopy (MRS) provides a non-invasive 'window' on biochemical processes within the body. Its use is no longer restricted to the field of research, with applications in clinical practice increasingly common. MRS can be conducted at high magnetic field strengths (typically 11-14 T) on body fluids, cell extracts and tissue samples, with new developments in whole-body magnetic resonance imaging (MRI) allowing clinical MRS at the end of a standard MRI examination, obtaining functional information in addition to anatomical information. We discuss the background physics the busy clinician needs to know before considering using the technique as an investigative tool. Some potential applications of hepatic and cerebral MRS in chronic liver disease are also discussed. ( J CLIN EXP HEPATOL 2015;5:320-328) T he biomedical applications of nuclear magnetic resonance (NMR) are twofold: magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). The applications of MRS as a research tool are extremely diverse, encompassing studies on isolated cells, body fluids and perfused organs at high magnetic field strengths in an experimental, laboratory-based setting and also in vivo studies using clinical MR systems. 1 In vivo clinical MRS on whole-body MRI scanners has been used to study the metabolism of well-defined regions of the human body, affording a non-invasive 'metabolic window' on a wide range of biochemical processes in the body, including the composition and function of human organs in vivo. 2 Clinical MRS developments have exploited many of the advances in MRI at the magnetic field strengths now used (typically 1.5-3.0 T) and the use of magnetic field gradients. The sensitivity and spatial resolution of MRS is a limiting factor in vivo, but parallel utilisation of in vitro MR spectroscopy of tissue extracts, body fluids and cell lines at much higher magnetic field strengths (typically 11.7-14.1 T) allows more definitive interpretation of the in vivo data. In this article, we aim to equip the clinician with knowledge of the background physics involved in MRS, so that informed decisions can be made for research studies. NUCLEAR MRSNMR refers to the behaviour of atoms subjected to a magnetic field. The phenomenon was first described in 1946 by Bloch and Purcell. Atoms with an odd mass number such as 1 H, 31 P and 13 C possess the quantum property of ''spin'' and behave as dipoles aligning along the axis of an applied magnetic field (Figure 1). During relaxation following excitation, radiofrequency signals are generated which can be expressed as a frequency spectrum. Hydrogen is the most abundant atom in living organisms and using high power magnetic fields on in vitro samples, high resolution metabolic spectra can be obtained with clearly defined metabolite peaks of small molecules (<2 kDa). NUCLEAR SPIN AND ORIENTATIONSNuclear resonance occurs because the nuclei of at least one of the isotopes of most elements possess a magnetic moment. A magnetic moment arises because the nucleus m...

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Section: Applicationsmentioning

confidence: 99%

Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians

Tognarelli

Dawood

Shariff

et al. 2015

Journal of Clinical and Experimental Hepatology

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“…It is widely recognized that the microbiome alters the metabolome in ways that are associated with, and in mouse models, cause disease (23, 24). It is therefore advantageous to assess these phenotypes concurrently and, in epidemiological studies, use sample collection methods that are amenable to multiple molecular analyses (25).…”

Section: Introductionmentioning

confidence: 99%

Comparison of Collection Methods for Fecal Samples for Discovery Metabolomics in Epidemiologic Studies

Loftfield

Vogtmann

Sampson

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background The gut metabolome may be associated with the incidence and progression of numerous diseases. The composition of the gut metabolome can be captured by measuring metabolite levels in the feces. However, there is little data describing the effect of fecal sample collection methods on metabolomic measures. Methods We collected fecal samples from eighteen volunteers using four methods: no solution, 95% ethanol, fecal occult blood test (FOBT) cards, and fecal immunochemical test (FIT). One set of samples was frozen after collection (day 0), and for 95% ethanol, FOBT, and FIT, a second set was frozen after 96 hours at room temperature. We evaluated 1) technical reproducibility within sample replicates, 2) stability after 96 hours at room temperature for 95% ethanol, FOBT, and FIT, and 3) concordance of metabolite measures with the putative “gold standard,” day 0 samples without solution. Results Intraclass correlation coefficients (ICC) estimating technical reproducibility were high for replicate samples for each collection method. ICCs estimating stability at room temperature were high for 95% ethanol and FOBT (median ICC>0.87) but not FIT (median ICC=0.52). Similarly, Spearman correlation coefficients (rs) estimating metabolite concordance with the “gold standard” were higher for 95% ethanol (median rs=0.82) and FOBT (median rs=0.70) than for FIT (median rs=0.40). Conclusions Metabolomic measurements appear reproducible and stable in fecal samples collected with 95% ethanol or FOBT. Concordance with the “gold standard” is highest with 95% ethanol and acceptable with FOBT. Impact Future epidemiologic studies should collect feces using 95% ethanol or FOBT if interested in studying fecal metabolomics.

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“…Factors such as genotype and environment can impact an individual's response to an intervention (109) . In the context of personalised nutrition, determination of an individual's metabolic-inflammatory phenotype prior to a nutritional intervention may be important.…”

Section: Future Perspectives: a Personalised Nutrition Approachmentioning

confidence: 99%

Impact of anti-inflammatory nutrients on obesity-associated metabolic-inflammation from childhood through to adulthood

et al. 2016

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Obesity-related metabolic conditions such as insulin resistance (IR), type 2 diabetes and CVD share a number of pathological features, one of which is metabolic-inflammation. Metabolic-inflammation results from the infiltration of immune cells into the adipose tissue, driving a pro-inflammatory environment, which can induce IR. Furthermore, resolution of inflammation, an active process wherein the immune system counteracts pro-inflammatory states, may be dysregulated in obesity. Anti-inflammatory nutritional interventions have focused on attenuating this pro-inflammatory environment. Furthermore, with inherent variability among individuals, establishing at-risk populations who respond favourably to nutritional intervention strategies is important. This review will focus on chronic low-grade metabolic-inflammation, resolution of inflammation and the putative role anti-inflammatory nutrients have as a potential therapy. Finally, in the context of personalised nutrition, the approaches used in defining individuals who respond favourably to nutritional interventions will be highlighted. With increasing prevalence of obesity in younger people, age-dependent biological processes, preventative strategies and therapeutic options are important to help protect against development of obesity-associated co-morbidities.

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The promise of metabolic phenotyping in gastroenterology and hepatology

Cited by 70 publications

References 153 publications

Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians

Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians

Comparison of Collection Methods for Fecal Samples for Discovery Metabolomics in Epidemiologic Studies

Impact of anti-inflammatory nutrients on obesity-associated metabolic-inflammation from childhood through to adulthood

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