Imperial College London

Dr. Jia Li

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Reader in Biological Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 3230jia.li

 
 
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Location

 

10.N2ACommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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136 results found

Anwar MA, Adesina-Georgiadis KN, Spagou K, Vorkas PA, Li JV, Shalhoub J, Holmes E, Davies AHet al., 2017, A comprehensive characterisation of the metabolic profile of varicose veins; implications in elaborating plausible cellular pathways for disease pathogenesis, Scientific Reports, Vol: 7, ISSN: 2045-2322

Metabolic phenotypes reflect both the genetic and environmental factors which contribute to the development of varicose veins (VV). This study utilises analytical techniques to provide a comprehensive metabolic picture of VV disease, with the aim of identifying putative cellular pathways of disease pathogenesis. VV (n = 80) and non-VV (n = 35) aqueous and lipid metabolite extracts were analysed using 600 MHz 1H Nuclear Magnetic Resonance spectroscopy and Ultra-Performance Liquid Chromatography Mass Spectrometry. A subset of tissue samples (8 subjects and 8 controls) were analysed for microRNA expression and the data analysed with mirBase (www.mirbase.org). Using Multivariate statistical analysis, Ingenuity pathway analysis software, DIANALAB database and published literature, the association of significant metabolites with relevant cellular pathways were understood. Higher concentrations of glutamate, taurine, myo-inositol, creatine and inosine were present in aqueous extracts and phosphatidylcholine, phosphatidylethanolamine and sphingomyelin in lipid extracts in the VV group compared with non-VV group. Out of 7 differentially expressed miRNAs, spearman correlation testing highlighted correlation of hsa-miR-642a-3p, hsa-miR-4459 and hsa-miR-135a-3p expression with inosine in the vein tissue, while miR-216a-5p, conversely, was correlated with phosphatidylcholine and phosphatidylethanolamine. Pathway analysis revealed an association of phosphatidylcholine and sphingomyelin with inflammation and myo-inositol with cellular proliferation.

Journal article

O'Hagan C, Li JV, Marchesi JR, Plummer S, Garaiova I, Good MAet al., 2017, Long-term multi-species Lactobacillus and Bifidobacterium dietary supplement enhances memory and changes regional brain metabolites in middle-aged rats, Neurobiology of Learning and Memory, Vol: 144, Pages: 36-47, ISSN: 1095-9564

Ageing is associated with changes in the gut microbiome that may contribute to age-related changes in cognition. Previous work has shown that dietary supplements with multi-species live microorganisms can influence brain function, including induction of hippocampal synaptic plasticity and production of brain derived neurotrophic factor, in both young and aged rodents. However, the effect of such dietary supplements on memory processes has been less well documented, particularly in the context of aging. The main aim of the present study was to examine the impact of a long-term dietary supplement with a multi-species live Lactobacillus and Bifidobacteria mixture (Lactobacillus acidophilus CUL60, L. acidophilus CUL21, Bifidobacterium bifidum CUL20 and B. lactis CUL34) on tests of memory and behavioural flexibility in 15–17-month-old male rats. Following behavioural testing, the hippocampus and prefrontal cortex was extracted and analysed ex vivo using 1H nuclear magnetic resonance (1H NMR) spectroscopy to examine brain metabolites. The results showed a small beneficial effect of the dietary supplement on watermaze spatial navigation and robust improvements in long-term object recognition memory and short-term memory for object-in-place associations. Short–term object novelty and object temporal order memory was not influenced by the dietary supplement in aging rats. 1H NMR analysis revealed diet-related regional-specific changes in brain metabolites; which indicated changes in several pathways contributing to modulation of neural signaling. These data suggest that chronic dietary supplement with multi-species live microorganisms can alter brain metabolites in aging rats and have beneficial effects on memory.

Journal article

Li JV, Swann J, Marchesi JR, 2017, Biology of the Microbiome 2: Metabolic Role, Gastroenterology Clinics of North America, Vol: 46, Pages: 37-47, ISSN: 0889-8553

The human microbiome is a new frontier in biology and one that is helping to define what it is to be human. Recently, we have begun to understand that the “communication” between the host and its microbiome is via a metabolic superhighway. By interrogating and understanding the molecules involved we may start to know who the main players are, and how we can modulate them and the mechanisms of health and disease.

Journal article

Anwar MA, Vorkas PA, Li J, Adesina-Georgiadis KN, Reslan OM, Raffetto JD, Want EJ, Khalil RA, Holmes E, Davies AHet al., 2016, Prolonged Mechanical Circumferential Stretch Induces Metabolic Changes in Rat Inferior Vena Cava, EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY, Vol: 52, Pages: 544-552, ISSN: 1078-5884

Journal article

Hodgson DM, Smith A, Dahale S, Stratford JP, Li JV, GrĂ¼ning A, Bushell ME, Marchesi JR, Avignone Rossa Cet al., 2016, Segregation of the Anodic Microbial Communities in a Microbial Fuel Cell Cascade., Frontiers in Microbiology, Vol: 7, Pages: 699-699, ISSN: 1664-302X

Metabolic interactions within microbial communities are essential for the efficient degradation of complex organic compounds, and underpin natural phenomena driven by microorganisms, such as the recycling of carbon-, nitrogen-, and sulfur-containing molecules. These metabolic interactions ultimately determine the function, activity and stability of the community, and therefore their understanding would be essential to steer processes where microbial communities are involved. This is exploited in the design of microbial fuel cells (MFCs), bioelectrochemical devices that convert the chemical energy present in substrates into electrical energy through the metabolic activity of microorganisms, either single species or communities. In this work, we analyzed the evolution of the microbial community structure in a cascade of MFCs inoculated with an anaerobic microbial community and continuously fed with a complex medium. The analysis of the composition of the anodic communities revealed the establishment of different communities in the anodes of the hydraulically connected MFCs, with a decrease in the abundance of fermentative taxa and a concurrent increase in respiratory taxa along the cascade. The analysis of the metabolites in the anodic suspension showed a metabolic shift between the first and last MFC, confirming the segregation of the anodic communities. Those results suggest a metabolic interaction mechanism between the predominant fermentative bacteria at the first stages of the cascade and the anaerobic respiratory electrogenic population in the latter stages, which is reflected in the observed increase in power output. We show that our experimental system represents an ideal platform for optimization of processes where the degradation of complex substrates is involved, as well as a potential tool for the study of metabolic interactions in complex microbial communities.

Journal article

Phetcharaburanin J, Lees H, Marchesi JR, Nicholson JK, Holmes E, Seyfried F, Li JVet al., 2016, Systemic Characterization of an Obese Phenotype in the Zucker Rat Model Defining Metabolic Axes of Energy Metab-olism and Host-Microbial Interactions, Journal of Proteome Research, Vol: 15, Pages: 1897-1906, ISSN: 1535-3907

The Zucker (fa/fa) rat is a valuable and extensively utilized model for obesity research. However, the metabolicnetworks underlying the systemic response in the obese Zucker rats remain to be elucidated. This information is importantto further our understanding of the circulation of the microbial or host-microbial metabolites and their impact on hostmetabolism. 1H Nuclear Magnetic Resonance spectroscopy-based metabolic profiling was used to probe global metabolicdifferences in portal vein and peripheral blood plasma, urine and fecal water between obese (fa/fa, n=12) and lean (fa/+,n=12) Zucker rats. Urinary concentrations of host-microbial co-metabolites were found to be significantly higher in leanZucker rats. Higher concentrations of fecal lactate, short chain fatty acids (SCFAs), 3-hydroxyphenyl propionic acid andglycerol, and lower levels of valine and glycine were observed in obese rats compared with lean animals. Regardless ofphenotype, concentrations of SCFAs, tricarboxylic acid cycle intermediates, and choline metabolites were higher in portalvein blood compared to peripheral blood. However, higher levels of succinate, phenylalanine and tyrosine were observedin portal vein blood compared with peripheral blood from lean rats but not in obese rats. Our findings indicate that theabsorption of propionate and acetate, choline and TMA are independent of the Zucker rat phenotypes. However, urinaryhost-microbial co-metabolites were highly associated with phenotypes, suggesting distinct gut microbial metabolic activitiesin lean and obese Zucker rats. This work advances our understanding of metabolic processes associated with obesity,particularly the metabolic functionality of the gut microbiota in the context of obesity.

Journal article

Gratton J, Phetcharaburanin J, Mullish BH, Williams HRT, Thursz M, Nicholson JK, Holmes E, Marchesi JR, Li Jet al., 2016, An optimized sample handling strategy for metabolic profiling of human feces, Analytical Chemistry, Vol: 88, Pages: 4661-4668, ISSN: 0003-2700

Fecal metabolites are being increasingly studied to unravel the host-gut microbial metabolic interactions. However, there are currently no guidelines for fecal sample collection and storage based on a systematic evaluation of the effect of time, storage temperature, storage duration and sampling strategy. Here we derive an optimized protocol for fecal sample handling with the aim of maximizing metabolic stability and minimizing sample degradation. Samples obtained from five healthy individuals were analyzed to assess topographical homogeneity of feces, and to evaluate storage duration-, temperature- and freeze-thaw cycle-induced metabolic changes in crude stool and fecal water using a 1H NMR spectroscopy-based metabolic profiling approach. Inter-individual variation was much greater than that attributable to storage conditions. Individual stool samples were found to be heterogeneous and spot sampling resulted in a high degree of metabolic variation. Crude fecal samples were remarkably unstable over time and exhibited distinct metabolic profiles at different storage temperatures. Microbial fermentation was the dominant driver in time-related changes observed in fecal samples stored at room temperature and this fermentative process was reduced when stored at 4°C. Crude fecal samples frozen at -20°C manifested elevated amino acids and nicotinate and depleted short chain fatty acids compared to crude fecal control samples. The relative concentrations of branched-chain and aromatic amino acids significantly increased in the freeze-thawed crude fecal samples, suggesting a release of microbial intracellular contents. The metabolic profiles of fecal water samples were more stable compared to crude samples. Our recommendation is that intact fecal samples should be collected, kept at 4°C or on ice during transportation, and extracted ideally within 1 h of collection, or a maximum of 24 h. Fecal water samples should be extracted from a representative amount (~15 g)

Journal article

Holmes E, Nicholson JK, Li J, Darzi AWet al., 2016, Phenotyping the patient journey, Metabolic Phenotyping in Personalized and Public Healthcare, Pages: 49-74, ISBN: 9780128003442

This chapter describes the concept of the patient journey, that is, the various interactions between a patient and a medical team as the patient first encounters the system, is diagnosed, treated, and followed up after whatever course of action was deemed appropriate. The various bottlenecks in the process are explained. As a new paradigm, the role of metabolic phenotyping (metabotyping) in monitoring the patient journey is discussed and examples are provided. The potential of such metabolic phenotyping in the clinic has implications in terms of stratified or personalized medicine, including adding information to aid diagnosis or to allow better prognosis, and these implications are listed. Finally, one example of the process, a dedicated phenome center, is illustrated.

Book chapter

Li JV, nicholson J, holmes E, darzi Aet al., 2016, Chapter 3 - Phenotyping the Patient Journey, Metabolic Phenotyping in Personalized and Public Healthcare, Publisher: Academic Press, ISBN: 9780128004142

HEALTHCARE. EDTED BY Elaine Holmes, Head of Computational and Systems Medicine Professor of Chemical ... Metabolic Phenotyping in Personalized and Public Healthcare authoritatively evaluates metabolic profiling and its uses ...

Book chapter

Turroni F, Milani C, Duranti S, Mancabelli L, Mangifesta M, Viappiani A, Lugli GA, Ferrario C, Gioiosa L, Ferrarini A, Li J, Palanza P, Delledonne M, van Sinderen D, Ventura Met al., 2016, Deciphering bifidobacterial-mediated metabolic interactions and their impact on gut microbiota by a multi-omics approach, ISME JOURNAL, Vol: 10, Pages: 1656-1668, ISSN: 1751-7362

Journal article

Mitra A, MacIntyre D, lee YS, Smith A, Marchesi J, Lehne B, Bhatia R, lyons D, Paraskevaidis E, Li J, holmes E, nicholson JK, bennett PR, kyrgiou Met al., 2015, Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity, Scientific Reports, Vol: 5, ISSN: 2045-2322

Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome diversity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene amplicons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL; n = 52), high-grade (HSIL; n = 92), invasive cervical cancer (ICC; n = 5) and healthy controls (n = 20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high-diversity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal = 2/20,10%; LSIL = 11/52,21%; HSIL = 25/92,27%; ICC = 2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P < 0.01), Anaerococcus tetradius (P < 0.05) and Peptostreptococcus anaerobius (P < 0.05) and lower levels of Lactobacillus jensenii (P < 0.01) compared to LSIL. Our results suggest advancing CIN disease severity is associated with increasing vaginal microbiota diversity and may be involved in regulating viral persistence and disease progression.

Journal article

Seyfried F, Miras AD, Rotzinger L, Nordbeck A, Corteville C, Li JV, Schlegel N, Hankir M, Fenske W, Otto C, Jurowich Cet al., 2015, Gastric Bypass-Related Effects on Glucose Control, β Cell Function and Morphology in the Obese Zucker Rat, Obesity Surgery, Vol: 26, Pages: 1228-1236, ISSN: 0960-8923

Journal article

Landy J, Walker AW, Li JV, Al-Hassi HO, Ronde E, English NR, Mann ER, Bernardo D, McLaughlin SD, Parkhill J, Ciclitira PJ, Clark SK, Knight SC, Hart ALet al., 2015, Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis, Scientific Reports, Vol: 5, ISSN: 2045-2322

Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and 1H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a “healthier” pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.

Journal article

Bower G, Athanasiou T, Isla AM, Harling L, Li JV, Holmes E, Efthimiou E, Darzi A, Ashrafian Het al., 2015, Bariatric surgery and nonalcoholic fatty liver disease, European Journal of Gastroenterology & Hepatology, Vol: 27, Pages: 755-768, ISSN: 0954-691X

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) is associated with the increasing global pandemic of obesity. These conditions cluster with type II diabetes mellitus and the metabolic syndrome to result in obesity-associated liver disease. The benefits of bariatric procedures on diabetes and the metabolic syndrome have been recognized for some time, and there is now mounting evidence to suggest that bariatric procedures improve liver histology and contribute to the beneficial resolution of NAFLD in obese patients. These beneficial effects derive from a number of weight-dependent and weight-independent mechanisms including surgical BRAVE actions (bile flow changes, restriction of stomach size, anatomical gastrointestinal rearrangement, vagal manipulation, enteric hormonal modulation) and subsequent effects such as reduced lipid intake, adipocytokine secretion, modulation of gut flora, improvements in insulin resistance and reduced inflammation. Here, we review the clinical investigations on bariatric procedures for NAFLD, in addition to the mounting mechanistic data supporting these findings. Elucidating the mechanisms by which bariatric procedures may resolve NAFLD can help enhance surgical approaches for metabolic hepatic dysfunction and also contribute toward developing the next generation of therapies aimed at reducing the burden of obesity-associated liver disease.

Journal article

Anwar MA, Vorkas PA, Li JV, Shalhoub J, Want EJ, Davies AH, Holmes Eet al., 2015, Optimization of metabolite extraction of human vein tissue for ultra performance liquid chromatography-mass spectrometry and nuclear magnetic resonance-based untargeted metabolic profiling, Analyst, Vol: 140, Pages: 7586-7597, ISSN: 1364-5528

Human vein tissue is an important matrix to examine when investigating vascular diseases with respect to understanding underlying disease mechanisms. Here, we report the development of an extraction protocol for multi-platform metabolic profiling of human vein tissue. For the first stage of the optimization, two different ratios of methanol/water and 5 organic solvents – namely dichloromethane, chloroform, isopropanol, hexane and methyl tert-butyl ether (MTBE) solutions with methanol – were tested for polar and organic compound extraction, respectively. The extraction output was assessed using 1H Nuclear Magnetic Resonance (NMR) spectroscopy and a panel of Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) methodologies. On the basis of the reproducibility of extraction replicates and metabolic coverage, the optimal aqueous (methanol/water) and organic (MTBE/methanol) solvents identified from the first stage were used in a sequential approach for metabolite extraction, altering the order of solvent-mixture addition. The combination of organic metabolite extraction with MTBE/methanol (3 : 1) followed by extraction of polar compounds with methanol/water (1 : 1) was shown to be the best method for extracting metabolites from human vein tissue in terms of reproducibility and number of signals detected and could be used as a single extraction procedure to serve both NMR and UPLC-MS analyses. Molecular classes such as triacylglycerols, phosphatidylcholines, phosphatidylethanolamines, sphingolipids, purines, and pyrimidines were reproducibly extracted. This study enabled an optimal extraction protocol for robust and more comprehensive metabolome coverage for human vein tissue. Many of the physiological and pathological processes affecting the composition of human vein tissue are common to other tissues and hence the extraction method developed in this study can be generically applied.

Journal article

O'Keefe SJ, Li JV, Lahti L, Ou J, Carbonero F, Mohammed K, Posma JM, Kinross J, Wahl E, Ruder E, Vipperla K, Naidoo V, Mtshali L, Tims S, Puylaert PG, DeLany J, Krasinskas A, Benefiel AC, Kaseb HO, Newton K, Nicholson JK, de Vos WM, Gaskins HR, Zoetendal EGet al., 2015, Fat, fibre and cancer risk in African Americans and rural Africans, Nature Communications, Vol: 6, Pages: 1-14, ISSN: 2041-1723

Rates of colon cancer are much higher in African Americans (65:100,000) than in rural South Africans (<5:100,000). The higher rates are associated with higher animal protein and fat, and lower fibre consumption, higher colonic secondary bile acids, lower colonic short-chain fatty acid quantities and higher mucosal proliferative biomarkers of cancer risk in otherwise healthy middle-aged volunteers. Here we investigate further the role of fat and fibre in this association. We performed 2-week food exchanges in subjects from the same populations, where African Americans were fed a high-fibre, low-fat African-style diet and rural Africans a high-fat, low-fibre western-style diet, under close supervision. In comparison with their usual diets, the food changes resulted in remarkable reciprocal changes in mucosal biomarkers of cancer risk and in aspects of the microbiota and metabolome known to affect cancer risk, best illustrated by increased saccharolytic fermentation and butyrogenesis, and suppressed secondary bile acid synthesis in the African Americans.

Journal article

Wu Q, Li JV, Seyfried F, le Roux CW, Ashrafian H, Athanasiou T, Fenske W, Darzi A, Nicholson JK, Holmes E, Gooderham NJet al., 2015, Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery., International Journal of Obesity, Vol: 2015, Pages: 1126-1134, ISSN: 1476-5497

Background/Objectives: Bariatric surgery offers sustained dramatic weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear.Subjects/MethodsWe mapped the co-ordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. Results: The response of circulating miRNAs to RYGB was striking and selective. Analysis of 14 significantly altered circulating miRNAs within a pathway context was suggestive of modulation of signalling pathways including G protein signalling, neurodegeneration, inflammation, and growth and apoptosis responses. Concomitant alterations in the metabolome indicated increased glucose transport, accelerated glycolysis and inhibited gluconeogenesis in the liver. Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. In mechanistic studies, manipulation of miRNA-122 levels in a cell model induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, TCA cycle, pentose phosphate shunt, fatty acid oxidation and gluconeogenesis, consistent with the findings of the in vivo surgery-mediated responses, indicating the powerful homeostatic activity of the miRNAs. Conclusions: The close association between energy metabolism, neuronal signalling and gut microbial metabolites derived from the circulating miRNA, plasma, urine and liver metabolite and gut hormone correlations further supports an enhanced gut-brain signaling, which we suggest is hormonally mediated by both traditional gut hormones and miRNAs. This transomic approach to map the crosstalk between the circulating miRNAome and metabolome offers opportunities to understand complex systems biology within a disease and interventional treatment setting.International Journal of Obesity accepted article previe

Journal article

Garaiova I, Muchova J, Nagyova Z, Wang D, Li JV, Orszaghova Z, Michael DR, Plummer SF, Durackova Zet al., 2015, Probiotics and vitamin C for the prevention of respiratory tract infections in children attending preschool: a randomised controlled pilot study, EUROPEAN JOURNAL OF CLINICAL NUTRITION, Vol: 69, Pages: 373-379, ISSN: 0954-3007

Journal article

Villasenor A, Kinross JM, Li JV, Penney N, Barton RH, Nicholson JK, Darzi A, Barbas C, Holmes Eet al., 2014, <SUP>1</SUP>H NMR Global Metabolic Phenotyping of Acute Pancreatitis in the Emergency Unit, JOURNAL OF PROTEOME RESEARCH, Vol: 13, Pages: 5362-5375, ISSN: 1535-3893

Journal article

Zhu X, Lei H, Wu J, Li JV, Tang H, Wang Yet al., 2014, Systemic Responses of BALB/c Mice to <i>Salmonella typhimurium</i> Infection, JOURNAL OF PROTEOME RESEARCH, Vol: 13, Pages: 4436-4445, ISSN: 1535-3893

Journal article

Mirnezami R, Jimenez B, Li JV, Kinross JM, Veselkov K, Goldin RD, Holmes E, Nicholson JK, Darzi Aet al., 2014, Rapid Diagnosis and Staging of Colorectal Cancer via High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HR-MAS NMR) Spectroscopy of Intact Tissue Biopsies, Annals of Surgery, Vol: 259, Pages: 1138-1149, ISSN: 0003-4932

Objective: To develop novel metabolite-based models for diagnosis and staging in colorectal cancer (CRC) using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy.Background: Previous studies have demonstrated that cancer cells harbor unique metabolic characteristics relative to healthy counterparts. This study sought to characterize metabolic properties in CRC using HR-MAS NMR spectroscopy.Methods: Between November 2010 and January 2012, 44 consecutive patients with confirmed CRC were recruited to a prospective observational study. Fresh tissue samples were obtained from center of tumor and 5 cm from tumor margin from surgical resection specimens. Samples were run in duplicate where tissue volume permitted to compensate for anticipated sample heterogeneity. Samples were subjected to HR-MAS NMR spectroscopic profiling and acquired spectral data were imported into SIMCA and MATLAB statistical software packages for unsupervised and supervised multivariate analysis.Results: A total of 171 spectra were acquired (center of tumor, n = 88; 5 cm from tumor margin, n = 83). Cancer tissue contained significantly increased levels of lactate (P < 0.005), taurine (P < 0.005), and isoglutamine (P < 0.005) and decreased levels of lipids/triglycerides (P < 0.005) relative to healthy mucosa (R2Y = 0.94; Q2Y = 0.72; area under the curve, 0.98). Colon cancer samples (n = 49) contained higher levels of acetate (P < 0.005) and arginine (P < 0.005) and lower levels of lactate (P < 0.005) relative to rectal cancer samples (n = 39). In addition unique metabolic profiles were observed for tumors of differing T-stage.Conclusions: HR-MAS NMR profiling demonstrates cancer-specific metabolic signatures in CRC and reveals metabolic differences between colonic and rectal cancers. In addition, this approach reveals that tumor metabolism undergoes modification during local tumor advancement, offering potential in future staging and therapeu

Journal article

Li JV, Holmes E, 2014, Chapter 11 Metabonomics for understanding gut microbiome and host metabolic interplay, The Human Microbiota and Microbiome, Editors: Marchesi, Publisher: CABI, ISBN: 9781780640495

This book presents a review of the current understanding of human microbiomes, the functions that they bring to the host, how we can model them, their role in health and disease and the methods used to explore them.

Book chapter

Kinross J, Li JV, Muirhead LJ, Nicholson Jet al., 2014, Nutritional modulation of the metabonome: applications of metabolic phenotyping in translational nutritional research, CURRENT OPINION IN GASTROENTEROLOGY, Vol: 30, Pages: 196-207, ISSN: 0267-1379

Journal article

Ashrafian H, Li J, Spagou K, Harling L, Masson P, Darzi A, Nicholson J, Holmes E, Athanasiou Tet al., 2014, Bariatric surgery modulates circulating and cardiac metabolites, Journal of Proteome Research, Vol: 13, Pages: 570-580, ISSN: 1535-3893

Bariatric procedures such as the Roux-en-Y gastric bypass (RYGB) operation offer profound metabolic enhancement in addition to their well-recognized weight loss effects. They are associated with significant reduction in cardiovascular disease risk and mortality, which suggests a surgical modification on cardiac metabolism. Metabolic phenotyping of the cardiac tissue and plasma postsurgery may give insight into cardioprotective mechanisms. The aim of the study was to compare the metabolic profiles of plasma and heart tissue extracts from RYGB- and sham-operated Wistar rats to identify the systemic and cardiac signature of metabolic surgery. A total of 27 male Wistar rats were housed individually for a week and subsequently underwent RYGB (n = 13) or sham (n = 14) operation. At week 8 postoperation, a total of 27 plasma samples and 16 heart tissue samples (8 RYGB; 8 Sham) were collected from animals and analyzed using 1H nuclear magnetic resonance (NMR) spectroscopy and ultra performance liquid chromatography (UPLC-MS) to characterize the global metabolite perturbation induced by RYGB operation. Plasma bile acids, phosphocholines, amino acids, energy-related metabolites, nucleosides and amine metabolites, and cardiac glycogen and amino acids were found to be altered in the RYGB operated group. Correlation networks were used to identify metabolite association. The metabolic phenotype of this bariatric surgical model inferred systematic change in both myocardial and systemic activity post surgery. The altered metabolic profile following bariatric surgery reflects an enhancement of cardiac energy metabolism through TCA cycle intermediates, cardiorenal protective activity, and biochemical caloric restriction. These surgically induced metabolic shifts identify some of the potential mechanisms that contribute toward bariatric cardioprotection through gut microbiota ecological fluxes and an enterocardiac axis to shield against metabolic syndrome of cardiac dysfunction.

Journal article

Li JV, Holmes E, 2014, Metabonomics for Understanding Gut Microbiome and Host Metabolic Interplay, HUMAN MICROBIOTA AND MICROBIOME, Editors: Marchesi, Publisher: CABI PUBLISHING-C A B INT, Pages: 171-189

Book chapter

Li JV, 2013, Metabonomics in Clinical Research, International Conference on Genomics

Conference paper

Zhao Y, Wu J, Li JV, Zhou N-Y, Tang H, Wang Yet al., 2013, Gut Microbiota Composition Modifies Fecal Metabolic Profiles in Mice, JOURNAL OF PROTEOME RESEARCH, Vol: 12, Pages: 2987-2999, ISSN: 1535-3893

Journal article

Li JV, 2013, Short-term reciprocal diet exchanges impact colonic fermentation and hydrogenotrophic microbiota for native Africans consuming a typical Western diet and African Americans consuming a traditional African diet, Digestive Disease Week

Conference paper

Seyfried F, Li JV, Miras AD, Cluny NL, Lannoo M, Fenske WK, Sharkey KA, Nicholson JK, le Roux CW, Holmes Eet al., 2013, Urinary Phenotyping Indicates Weight Loss-Independent Metabolic Effects of Roux-en-Y Gastric Bypass in Mice, JOURNAL OF PROTEOME RESEARCH, Vol: 12, Pages: 1245-1253, ISSN: 1535-3893

Journal article

Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R, Cheng J, Kau AL, Rich SS, Concannon P, Mychaleckyj JC, Liu J, Houpt E, Li JV, Holmes E, Nicholson JK, Knights D, Ursell LK, Knight R, Gordon JIet al., 2013, Gut microbiomes of Malawian twin pairs discordant for kwashiorkor, science.

Journal article

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