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

Hartman TJ, Christie J, Wilson A, Ziegler TR, Methe B, Flanders WD, Rolls BJ, Loye Eberhart B, Li JV, Huneault H, Cousineau B, Perez MR, O'Keefe SJDet al., 2024, Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer trial study protocol: a randomised clinical trial of fibre-rich legumes targeting the gut microbiome, metabolome and gut transit time of overweight and obese patients with a history of noncancerous adenomatous polyps., BMJ Open, Vol: 14

INTRODUCTION: Recently published studies support the beneficial effects of consuming fibre-rich legumes, such as cooked dry beans, to improve metabolic health and reduce cancer risk. In participants with overweight/obesity and a history of colorectal polyps, the Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer randomised clinical trial will test whether a high-fibre diet featuring legumes will simultaneously facilitate weight reduction and suppress colonic mucosal biomarkers of colorectal cancer (CRC). METHODS/DESIGN: This study is designed to characterise changes in (1) body weight; (2) biomarkers of insulin resistance and systemic inflammation; (3) compositional and functional profiles of the faecal microbiome and metabolome; (4) mucosal biomarkers of CRC risk and (5) gut transit. Approximately 60 overweight or obese adults with a history of noncancerous adenomatous polyps within the previous 3 years will be recruited and randomised to one of two weight-loss diets. Following a 1-week run-in, participants in the intervention arm will receive preportioned high-fibre legume-rich entrées for two meals/day in months 1-3 and one meal/day in months 4-6. In the control arm, entrées will replace legumes with lean protein sources (eg, chicken). Both groups will receive in-person and written guidance to include nutritionally balanced sides with energy intake to lose 1-2 pounds per week. ETHICS AND DISSEMINATION: The National Institutes of Health fund this ongoing 5-year study through a National Cancer Institute grant (5R01CA245063) awarded to Emory University with a subaward to the University of Pittsburgh. The study protocol was approved by the Emory Institutional Review Board (IRB approval number: 00000563). TRIAL REGISTRATION NUMBER: NCT04780477.

Journal article

Wang M, Guo J, Hart AL, Li Jet al., 2023, Indole-3-aldehyde reduces inflammatory responses and restores intestinal epithelial barrier function partially via aryl hydrocarbon receptor (AhR) in experimental colitis models, Journal of Inflammation Research, Vol: 16, Pages: 5845-5864, ISSN: 1178-7031

Purpose:Indole-3-aldehyde (IAld) has been shown to improve intestinal epithelial barrier (IEB) function through the aryl hydrocarbon receptor (AhR) in murine colitis models. However, the impact of IAld on intestinal tissue inflammation remains unexplored. This study aimed to investigate the effects of IAld on the inflammatory responses of the gut both in vivo and in vitro and probe the mechanisms by which IAld attenuates colitis.Methods:The effects of IAld on phenotypic changes, pro-inflammatory cytokines, IEB functions and the faecal bacterial composition in mice with dextran sulfate sodium salt (DSS)-induced colitis were assessed. Macrophage cells and intestinal epithelial cells were stimulated with lipopolysaccharide (LPS), and the effects of IAld on the inflammatory responses and IBE functions were measured.Results:IAld reduced IL-6, IL-1β and TNF-α protein levels in both colonic tissues from the mice with colitis and LPS-stimulated macrophage cells. The IAld-mediated reduction of IL-6 but not IL-1β and TNF-α was through AhR activation. Furthermore, nuclear factor-κB pathway was found to be inhibited by IAld treatment via AhR activation both in vivo and in vitro. Gut permeability was significantly improved by IAld in both DSS-treated mice and LPS-stimulated Caco-2 cells. This observation is consistent with downregulation of phosphorylated myosin light chain through AhR activation. IAld did not appear to have an effect on the bacterial composition in mice with colitis despite the reduced colonic inflammatory responses.Conclusion:IAld improved DSS-induced colitis by inhibiting the inflammatory responses and restoring IEB function, partially via AhR activation. This work provided insight into the function of IAld in modulating gut inflammation.

Journal article

Hu C, Wang B, Liu Z, Chen Q, Ishikawa M, Lin H, Lian Q, Li J, Li J, Ma Det al., 2023, Sevoflurane but not propofol enhances ovarian cancer cell biology through regulating cellular metabolic and signaling mechanisms, CELL BIOLOGY AND TOXICOLOGY, Vol: 39, Pages: 1395-1411, ISSN: 0742-2091

Journal article

Harvey N, Takis PG, Lindon JC, Li JV, Jiménez Bet al., 2023, Optimization of diffusion-ordered NMR spectroscopy experiments for high-throughput automation in human metabolic phenotyping, Analytical Chemistry, Vol: 95, Pages: 3147-3152, ISSN: 0003-2700

The diffusion-ordered nuclear magnetic resonance spectroscopy (DOSY) experiment allows the calculation of diffusion coefficient values of metabolites in complex mixtures. However, this experiment has not yet been broadly used for metabolic profiling due to lack of a standardized protocol. Here we propose a pipeline for the DOSY experimental setup and data processing in metabolic phenotyping studies. Due to the complexity of biological samples, three experiments (a standard DOSY, a relaxation-edited DOSY, and a diffusion-edited DOSY) have been optimized to provide DOSY metabolic profiles with peak-picked diffusion coefficients for over 90% of signals visible in the one-dimensional 1H general biofluid profile in as little as 3 min 36 s. The developed parameter sets and tools are straightforward to implement and can facilitate the use of DOSY for metabolic profiling of human blood plasma and urine samples.

Journal article

Li J, Gooderham N, Alotaibi A, 2023, Tumour necrosis factor-alpha (TNF-α)-induced metastatic phenotype in colorectal cancer epithelial cells: mechanistic support for the role of microRNA-21, Cancers, Vol: 15, Pages: 1-19, ISSN: 2072-6694

The progression of colorectal cancer is promoted by changes in the genetic makeup of tumour cells giving them potential to leave the site of their origin to seed new metastatic tumours in other tissue; inflammation at the tumour site is a driver of these changes. Tumour necrosis factor-alpha is a pro-inflammatory molecule that is associated with the progression of metastatic cancer. Small biologically active RNAs, microRNAs, target the production of specific proteins and are proposed as agents of tumour change. One agent, microRNA-21, shown to be present in colorectal cancer, is known to target the formation of proteins involved in metastatic changes in cells. We investigated the relationship between TNF-α and microRNA-21 in colorectal cancer cells and show their involvement in promoting cell changes indicative of the metastatic state. In summary, we provide mechanistic support for a role of microRNA-21 in tumour necrosis factor-alpha promotion of cancer cell metastatic change.

Journal article

Radhakrishnan ST, Gallagher KI, Mullish BH, Serrano Contreras JI, Alexander JL, Miguens Blanco J, Danckert NP, Valdivia Garcia M, Hopkins BJ, Ghai A, Ayub A, Li JV, Marchesi JR, Williams HRTet al., 2023, Rectal swabs as a viable alternative to faecal sampling for the analysis of gut microbiota functionality and composition, Scientific Reports, Vol: 13, Pages: 1-9, ISSN: 2045-2322

Faecal or biopsy samples are frequently used to analyse the gut microbiota, but issues remain with the provision and collection of such samples. Rectal swabs are widely-utilised in clinical practice and previous data demonstrate their potential role in microbiota analyses; however, studies to date have been heterogenous, and there are a particular lack of data concerning the utility of swabs for the analysis of the microbiota’s functionality and metabolome. We compared paired stool and rectal swab samples from healthy individuals to investigate whether rectal swabs are a reliable proxy for faecal sampling. There were no significant differences in key alpha and beta diversity measures between swab and faecal samples, and inter-subject variability was preserved. Additionally, no significant differences were demonstrated in abundance of major annotated phyla. Inferred gut functionality using Tax4Fun2 showed excellent correlation between the two sampling techniques (Pearson’s coefficient r = 0.9217, P < 0.0001). Proton nuclear magnetic resonance (1H NMR) spectroscopy enabled the detection of 20 metabolites, with overall excellent correlation identified between rectal swab and faecal samples for levels all metabolites collectively, although more variable degrees of association between swab and stool for levels of individual metabolites. These data support the utility of rectal swabs in both compositional and functional analyses of the gut microbiota.

Journal article

Yates JR, Cristea IM, Dong M-Q, Eyers CE, LaBaer J, Li JV, Nicholson JK, Overall CM, Palmblad M, Slavov Net al., 2022, Want to Publish in <i>JPR</i>? This Is What You Need to Know!, JOURNAL OF PROTEOME RESEARCH, Vol: 21, Pages: 2837-2839, ISSN: 1535-3893

Journal article

Valdivia-Garcia MA, Chappell KE, Camuzeaux S, Olmo-Garcia L, van der Sluis VH, Radhakrishnan ST, Stephens H, Bouri S, Braz LMDC, Williams HT, Lewis MR, Frost G, Li Jet al., 2022, Improved quantitation of short-chain carboxylic acids in human biofluids using 3-nitrophenylhydrazine derivatization and liquid chromatography with tandem mass spectrometry (LC-MS/MS), JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 221, ISSN: 0731-7085

Journal article

Nahok K, Selmi C, Sukmak M, Phetcharaburanin J, Li JV, Silsirivanit A, Thanan R, Sharma A, Anutrakulchai S, Hammock BD, Cha'on Uet al., 2022, Reply to Chao et al. Comment on "Nahok et al. Monosodium Glutamate Induces Changes in Hepatic and Renal Metabolic Profiles and Gut Microbiome of Wistar Rats. <i>Nutrients</i> 2021, <i>13</i>, 1865", NUTRIENTS, Vol: 14

Journal article

Haonon O, Liu Z, Dangtakot R, Pinlaor P, Puapairoj A, Cha'on U, Intuyod K, Pongking T, Jantawong C, Sengthong C, Chaidee A, Onsurathum S, Li J, Pinlaor Set al., 2022, <i>Opisthorchis viverrini</i> infection induces metabolic disturbances in hamsters fed with high fat/high fructose diets: Implications for liver and kidney pathologies, JOURNAL OF NUTRITIONAL BIOCHEMISTRY, Vol: 107, ISSN: 0955-2863

Journal article

Webberley TS, Masetti G, Bevan RJ, Kerry-Smith J, Jack AA, Michael DR, Thomas S, Glymenaki M, Li J, McDonald JAK, John D, Morgan JE, Marchesi JR, Good MA, Plummer SF, Hughes TRet al., 2022, The Impact of Probiotic Supplementation on Cognitive, Pathological and Metabolic Markers in a Transgenic Mouse Model of Alzheimer's Disease, FRONTIERS IN NEUROSCIENCE, Vol: 16

Journal article

Ruban A, Miras A, glaysher M, Goldstone A, Teare Jet al., 2022, Duodenal-jejunal bypass liner for the management of Type 2 diabetes and obesity: a multicenter randomized controlled trial, Annals of Surgery, Vol: 275, Pages: 440-447, ISSN: 0003-4932

Objective: The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation.Summary Background Data: This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery.Methods: In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months.Results: There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44–2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8–39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group.Conclusions: The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions.Trial Registration: ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research

Journal article

Suksawat M, Phetcharaburanin J, Klanrit P, Namwat N, Khuntikeo N, Titapun A, Jarearnrat A, Vilayhong V, Sa-ngiamwibool P, Techasen A, Wangwiwatsin A, Mahalapbutr P, Li JV, Loilome Wet al., 2022, Metabolic Phenotyping Predicts Gemcitabine and Cisplatin Chemosensitivity in Patients With Cholangiocarcinoma, FRONTIERS IN PUBLIC HEALTH, Vol: 10

Journal article

Jones B, Sands C, Alexiadou K, Minnion J, Tharakan G, Behary P, Ahmed A, Purkayastha S, Lewis M, Bloom S, Li J, Tan Tet al., 2022, The metabolomic effects of tripeptide gut hormone infusion compared to Roux-en-Y gastric bypass and caloric restriction, Journal of Clinical Endocrinology and Metabolism, Vol: 107, Pages: e767-e782, ISSN: 0021-972X

Context: The gut-derived peptide hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY) are regulators of energy intake and glucose homeostasis, and are thought to contribute to the glucose-lowering effects of bariatric surgery. Objective: To establish the metabolomic effects of a combined infusion of GLP-1, OXM and PYY (tripeptide “GOP”) in comparison to a placebo infusion, Roux-en-Y gastric bypass (RYGB) surgery, and a very low-calorie diet (VLCD). Design and setting: Sub-analysis of a single-blind, randomised, placebo-controlled study of GOP infusion (ClinicalTrials.gov NCT01945840), including VLCD and RYGB comparator groups. Patients and interventions: 25 obese patients with type 2 diabetes or prediabetes were randomly allocated to receive a 4-week subcutaneous infusion of GOP (n=14) or 0.9% saline control (SAL; n=11). An additional 22 patients followed a VLCD, and 21 underwent RYGB surgery. Main outcome measures: Plasma and urine samples collected at baseline and 4 weeks into each intervention were subjected to cross-platform metabolomic analysis, followed by unsupervised and supervised modelling approaches to identify similarities and differences between the effects of each intervention. Results: Aside from glucose, very few metabolites were affected by GOP, contrasting with major metabolomic changes seen with VLCD and RYGB. Conclusions: Treatment with GOP provides a powerful glucose-lowering effect but does not replicate the broader metabolomic changes seen with VLCD and RYGB. The contribution of these metabolomic changes to the clinical benefits of RYGB remains to be elucidated.

Journal article

Radhakrishnan ST, Alexander JL, Mullish BH, Gallagher KI, Powell N, Hicks LC, Hart AL, Li JV, Marchesi JR, Williams HRTet al., 2022, Systematic Review: The association between the gut microbiota and medical therapies in inflammatory bowel disease, Alimentary Pharmacology and Therapeutics, Vol: 55, Pages: 26-48, ISSN: 0269-2813

BackgroundThe gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype.AimsTo evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota.MethodsWe conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included.ResultsWe screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α-diversity was observed in responders versus non-responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post-treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti-TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate-treated patients.ConclusionsBoth gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments.

Journal article

Ferreira MR, Sands CJ, Li J, Andreyev JN, Chekmeneva E, Gulliford S, Marchesi J, Lewis MR, Dearnaley DPet al., 2021, Impact of pelvic radiation therapy for prostate cancer on global metabolic profiles and microbiota-driven gastrointestinal late side effects: a longitudinal observational study, International Journal of Radiation: Oncology - Biology - Physics, Vol: 111, Pages: 1204-1213, ISSN: 0360-3016

PurposeRadiation therapy to the prostate and pelvic lymph nodes (PLNRT) is part of the curative treatment of high-risk prostate cancer. Yet, the broader influence of radiation therapy on patient physiology is poorly understood. We conducted comprehensive global metabolomic profiling of urine, plasma, and stools sampled from patients undergoing PLNRT for high-risk prostate cancer.Methods and MaterialsSamples were taken from 32 patients at 6 timepoints: baseline, 2 to 3 and 4 to 5 weeks of PLNRT; and 3, 6, and 12 months after PLNRT. We characterized the global metabolome of urine and plasma using 1H nuclear magnetic resonance spectroscopy and ultraperformance liquid chromatography-mass spectrometry, and of stools with nuclear magnetic resonance. Linear mixed-effects modeling was used to investigate metabolic changes between timepoints for each biofluid and assay and determine metabolites of interest.ResultsMetabolites in urine, plasma and stools changed significantly after PLNRT initiation. Metabolic profiles did not return to baseline up to 1 year post-PLNRT in any biofluid. Molecules associated with cardiovascular risk were increased in plasma. Pre-PLNRT fecal butyrate levels directly associated with increasing gastrointestinal side effects, as did a sharper fall in those levels during and up to 1 year postradiation therapy, mirroring our previous results with metataxonomics.ConclusionsWe showed for the first time that an overall metabolic effect is observed in patients undergoing PLNRT up to 1 year posttreatment. These metabolic changes may effect on long-term morbidity after treatment, which warrants further investigation.

Journal article

Koller KR, Wilson A, Normolle DP, Nicholson JK, Li JV, Kinross J, Lee FR, Flanagan CA, Merculieff ZT, Iyer P, Lammers DL, Thomas TK, O'Keefe SJDet al., 2021, Dietary fibre to reduce colon cancer risk in Alaska Native people: the Alaska FIRST randomised clinical trial protocol., BMJ Open, Vol: 11, Pages: 1-9, ISSN: 2044-6055

INTRODUCTION: Diet, shown to impact colorectal cancer (CRC) risk, is a modifiable environmental factor. Fibre foods fermented by gut microbiota produce metabolites that not only provide food for the colonic epithelium but also exert regulatory effects on colonic mucosal inflammation and proliferation. We describe methods used in a double-blinded, randomised, controlled trial with Alaska Native (AN) people to determine if dietary fibre supplementation can substantially reduce CRC risk among people with the highest reported CRC incidence worldwide. METHODS AND ANALYSES: Eligible patients undergoing routine screening colonoscopy consent to baseline assessments and specimen/data collection (blood, urine, stool, saliva, breath and colon mucosal biopsies) at the time of colonoscopy. Following an 8-week stabilisation period to re-establish normal gut microbiota post colonoscopy, study personnel randomise participants to either a high fibre supplement (resistant starch, n=30) or placebo (digestible starch, n=30) condition, repeating stool sample collection. During the 28-day supplement trial, each participant consumes their usual diet plus their supplement under direct observation. On day 29, participants undergo a flexible sigmoidoscopy to obtain mucosal biopsy samples to measure the effect of the supplement on inflammatory and proliferative biomarkers of cancer risk, with follow-up assessments and data/specimen collection similar to baseline. Secondary outcome measures include the impact of a high fibre supplement on the oral and colonic microbiome and biofluid metabolome. ETHICS AND DISSEMINATION: Approvals were obtained from the Alaska Area and University of Pittsburgh Institutional Review Boards and Alaska Native Tribal Health Consortium and Southcentral Foundation research review bodies. A data safety monitoring board, material transfer agreements and weekly study team meetings provide regular oversight throughout the study. Study findings will first be shared with AN

Journal article

Haonon O, Liu Z, Dangtakot R, Intuyod K, Pinlaor P, Puapairoj A, Cha'on U, Sengthong C, Pongking T, Onsurathum S, Yingklang M, Phetcharaburanin J, Li J, Pinlaor Set al., 2021, Opisthorchis viverrini Infection Induces Metabolic and Fecal Microbial Disturbances in Association with Liver and Kidney Pathologies in Hamsters, JOURNAL OF PROTEOME RESEARCH, Vol: 20, Pages: 3940-3951, ISSN: 1535-3893

Journal article

Hu C, Iwasaki M, Liu Z, Wang B, Li X, Lin H, Li J, Li JV, Lian Q, Ma Det al., 2021, Lung but not brain cancer cell malignancy inhibited by commonly used anesthetic propofol during surgery: Implication of reducing cancer recurrence risk, Journal of Advanced Research, Vol: 31, Pages: 1-12, ISSN: 2090-1232

IntroductionIntravenous anesthesia with propofol was reported to improve cancer surgical outcomes when compared with inhalational anesthesia. However, the underlying molecular mechanisms largely remain unknown.ObjectivesThe anti-tumor effects of propofol and the possible underlying mechanism including altered metabolic and signaling pathways were studied in the current study.MethodsThe cell viability, proliferation, migration, and invasion of cancer cells were analyzed with CCK-8, Ki-67 staining, wound healing, and Transwell assay, respectively. The protein changes were analyzed with Western blot and immunofluorescent staining. The metabolomics alteration was studied with 1H-NMR spectroscopy. The gene expression regulations were analyzed with PCR gene array and qRT-PCR experiments.ResultsIn this study, we found that propofol reduced cell viability and inhibited cell proliferation, migration and invasion of lung cancer cells, but not neuroglioma cells. In lung cancer cells, propofol downregulated glucose transporter 1 (GLUT1), mitochondrial pyruvate carrier 1 (MPC1), p-Akt, p-Erk1/2, and hypoxia- inducible factor 1 alpha (HIF-1 α ) expressions and upregulated pigment epithelium-derived factor (PEDF) expression. Propofol increased intracellular glutamate and glycine but decreased acetate and formate whilst increased glucose, lactate, glutamine, succinate, pyruvate, arginine, valine, isoleucine, and leucine and glycerol, and decreased acetate, ethanol, isopropanol in the culture media of lung cancer cells. Furthermore, VEGFA, CTBP1, CST7, CTSK, CXCL12, and CXCR4 gene expressions were downregulated, while NR4A3, RB1, NME1, MTSS1, NME4, SYK, APC, and FAT1 were upregulated following the propofol treatment. Consistent with the phenotypical changes, these molecular and metabolic changes were not found in the neuroglioma cells.ConclusionOur findings indicated anti-tumor effects of propofol on the lung cancer but not brain cancer, through the regulation of tumor metasta

Journal article

Alotaibi A, Li J, Gooderham N, 2021, Tumour necrosis factor-α (TNF-α) enhances dietary carcinogen-induced DNA damage in colorectal cancer epithelial cells through activation of JNK signaling pathway, Toxicology, Vol: 457, ISSN: 0300-483X

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer death. Benzo[a]pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazol [4,5-b] pyridine (PhIP) present in cooked meat are pro-carcinogens and considered to be potential risk factors for CRC. Their carcinogenic and mutagenic effects require metabolic activation primarily by cytochrome P450 1 family enzymes (CYPs); the expression of these enzymes can be modulated by aryl hydrocarbon receptor (AhR) activation and the tumour microenvironment, involving mediators of inflammation. In this study, we hypothesized that tumour necrosis factor-α (TNF-α), a key mediator of inflammation, modulates BaP- and PhIP-induced DNA damage in colon cancer epithelial cells. Importantly, we observed that TNF-α alone (0.1–100 pg/ml) induced DNA damage (micronuclei formation) in HCT-116 cells and co-treatment of TNF-α with BaP or PhIP showed higher levels of DNA damage compared to the individual single treatments. TNF-α alone or in combination with BaP or PhIP did not affect the expression levels of CYP1A1 and CYP1B1 (target genes of AhR signaling pathways). The DNA damage induced by TNF-α was elevated in p53 null HTC-116 cells compared to wild type cells, suggesting that TNF-α-induced DNA damage is suppressed by functional p53. In contrast, p53 status failed to affect BaP and PhIP induced micronucleus frequency. Furthermore, JNK and NF-κB signaling pathway were activated by TNF-α treatment but only inhibition of JNK significantly reduced TNF-α-induced DNA damage. Collectively, these findings suggest that TNF-α induced DNA damage involves JNK signaling pathway rather than AhR and NF-κB pathways in colon cancer epithelial cells.

Journal article

Li J, 2021, Roux-en-Y Gastric bypass-induced bacterial perturbation contributes to altered host-bacterial co-metabolic phenotype, Microbiome, Vol: 9, ISSN: 2049-2618

BACKGROUND: Bariatric surgery, used to achieve effective weight loss in individuals with severe obesity, modifies the gut microbiota and systemic metabolism in both humans and animal models. The aim of the current study was to understand better the metabolic functions of the altered gut microbiome by conducting deep phenotyping of bariatric surgery patients and bacterial culturing to investigate causality of the metabolic observations. METHODS: Three bariatric cohorts (n = 84, n = 14 and n = 9) with patients who had undergone Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) or laparoscopic gastric banding (LGB), respectively, were enrolled. Metabolic and 16S rRNA bacterial profiles were compared between pre- and post-surgery. Faeces from RYGB patients and bacterial isolates were cultured to experimentally associate the observed metabolic changes in biofluids with the altered gut microbiome. RESULTS: Compared to SG and LGB, RYGB induced the greatest weight loss and most profound metabolic and bacterial changes. RYGB patients showed increased aromatic amino acids-based host-bacterial co-metabolism, resulting in increased urinary excretion of 4-hydroxyphenylacetate, phenylacetylglutamine, 4-cresyl sulphate and indoxyl sulphate, and increased faecal excretion of tyramine and phenylacetate. Bacterial degradation of choline was increased as evidenced by altered urinary trimethylamine-N-oxide and dimethylamine excretion and faecal concentrations of dimethylamine. RYGB patients' bacteria had a greater capacity to produce tyramine from tyrosine, phenylalanine to phenylacetate and tryptophan to indole and tryptamine, compared to the microbiota from non-surgery, normal weight individuals. 3-Hydroxydicarboxylic acid metabolism and urinary excretion of primary bile acids, serum BCAAs and dimethyl sulfone were also perturbed following bariatric surgery. CONCLUSION: Altered bacterial composition and metabolism contribute to metabolic observations in biofluid

Journal article

Nahok K, Phetcharaburanin J, Li J, Silsirivanit A, Thanan R, Boonnate P, Joonhuathon J, Sharma A, Anutrakulchai S, Selmi C, Cha'on Uet al., 2021, Monosodium Glutamate Induces Changes in Hepatic and Renal Metabolic Profiles and Gut Microbiome of Wistar Rats, NUTRIENTS, Vol: 13

Journal article

Barker GF, Pechlivanis A, Bello AT, Chrysostomou D, Mullish BH, Marchesi J, Posma JM, Kinross JM, Nicholson J, O'Keefe SJ, Li JVet al., 2021, Aa022 a high-fiber low-fat diet increases fecal levels of lithocholic acid derivative 3-ketocholanic acid, Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S393-S394, ISSN: 0016-5085

Conference paper

Radhakrishnan ST, Mullish BH, Gallagher K, Alexander JL, Danckert NP, Blanco JM, Serrano-Contreras JI, Valdivia-Garcia M, Hopkins BJ, Ghai A, Li JV, Marchesi J, Williams HRet al., 2021, RECTAL SWABS AS A VIABLE ALTERNATIVE TO FECAL SAMPLING FOR THE ANALYSIS OF GUT MICROBIOME FUNCTIONALITY AS WELL AS COMPOSITION, Society-for-Surgery-of-the-Alimentary-Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S733-S733, ISSN: 0016-5085

Conference paper

Glymenaki M, Curio S, Cabrera PM, Ashrafian H, Guerra N, Li JVet al., 2021, TYRAMINE IS A POTENTIAL CONTRIBUTOR TO INCREASED COLON CANCER RISK FOLLOWING BARIATRIC SURGERY, Society-for-Surgery-of-the-Alimentary-Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S738-S738, ISSN: 0016-5085

Conference paper

Gholkar MS, Li J, Daswani PG, Tetali P, Birdi TJet al., 2021, <SUP>1</SUP>H nuclear magnetic resonance-based metabolite profiling of guava leaf extract: an attempt to develop a prototype for standardization of plant extracts, BMC COMPLEMENTARY MEDICINE AND THERAPIES, Vol: 21

Journal article

Jukes Z, Freier A, Glymenaki M, Brown R, Parry L, Want E, Vorkas PA, Li JVet al., 2021, Lipid profiling of mouse intestinal organoids for studying APC mutations, Bioscience Reports: molecular and cellular biology of the cell surface, Vol: 41, Pages: 1-11, ISSN: 0144-8463

Inactivating mutations including both germline and somatic mutations in the adenomatous polyposis coli (APC) gene drives most familial and sporadic colorectal cancers. Understanding the metabolic implications of this mutation will aid to establish its wider impact on cellular behaviour and potentially inform clinical decisions. However, to date, alterations in lipid metabolism induced by APC mutations remain unclear. Intestinal organoids have gained widespread popularity in studying colorectal cancer and chemotherapies, because their 3D structure more accurately mimics an in vivo environment. Here, we aimed to investigate intra-cellular lipid disturbances induced by APC gene mutations in intestinal organoids using a reversed-phase ultra-high-performance liquid chromatography mass spectrometry (RP-UHPLC-MS)-based lipid profiling method. Lipids of the organoids grown from either wild-type (WT) or mice with APC mutations (Lgr5–EGFP-IRES-CreERT2Apcfl/fl) were extracted and analysed using RP-UHPLC-MS. Levels of phospholipids (e.g. PC(16:0/16:0), PC(18:1/20:0), PC(38:0), PC(18:1/22:1)), ceramides (e.g. Cer(d18:0/22:0), Cer(d42:0), Cer(d18:1/24:1)) and hexosylceramides (e.g. HexCer(d18:1/16:0), HexCer(d18:1/22:0)) were higher in Apcfl/fl organoids, whereas levels of sphingomyelins (e.g. SM(d18:1/14:0), SM(d18:1/16:0)) were lower compared with WT. These observations indicate that cellular metabolism of sphingomyelin was up-regulated, resulting in the cellular accumulation of ceramides and production of HexCer due to the absence of Apcfl/fl in the organoids. Our observations demonstrated lipid profiling of organoids and provided an enhanced insight into the effects of the APC mutations on lipid metabolism, making for a valuable addition to screening options of the organoid lipidome.

Journal article

Promraksa B, Katrun P, Phetcharaburanin J, Kittirat Y, Namwat N, Techasen A, Li JV, Loilome Wet al., 2021, Metabolic Changes of Cholangiocarcinoma Cells in Response to Coniferyl Alcohol Treatment, BIOMOLECULES, Vol: 11

Journal article

Ritler D, Rufener R, Li JV, Kämpfer U, Müller J, Bühr C, Schürch S, Lundström-Stadelmann Bet al., 2021, Author Correction: In vitro metabolomic footprint of the Echinococcus multilocularis metacestode., Sci Rep, Vol: 11

Journal article

Seyfried F, Phetcharaburanin J, Glymenaki M, Nordbeck A, Hankir M, Nicholson J, Holmes E, Marchesi J, Li Jet al., 2021, Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss, Gut Microbes, Vol: 13, Pages: 1-20, ISSN: 1949-0976

Mechanisms of Roux-en-Y gastric bypass (RYGB) surgery are not fully understood. This study aimed to investigate weight loss-independent bacterial and metabolic changes, as well as the absorption of bacterial metabolites and bile acids through the hepatic portal system following RYGB surgery. Three groups of obese Zucker (fa/fa) rats were included: RYGB (n = 11), sham surgery and body weight matched with RYGB (Sham-BWM, n = 5), and sham surgery fed ad libitum (Sham-obese, n = 5). Urine and feces were collected at multiple time points, with portal vein and peripheral blood obtained at the end of the study. Metabolic phenotyping approaches and 16S rRNA gene sequencing were used to determine the biochemical and bacterial composition of the samples, respectively. RYGB surgery-induced distinct metabolic and bacterial disturbances, which were independent of weight loss through caloric restriction. RYGB resulted in lower absorption of phenylalanine and choline, and higher urinary concentrations of host-bacterial co-metabolites (e.g., phenylacetylglycine, indoxyl sulfate), together with higher fecal trimethylamine, suggesting enhanced bacterial aromatic amino acid and choline metabolism. Short chain fatty acids (SCFAs) were lower in feces and portal vein blood from RYGB group compared to Sham-BWM, accompanied with lower abundances of Lactobacillaceae, and Ruminococcaceae known to contain SCFA producers, indicating reduced bacterial fiber fermentation. Fecal γ-amino butyric acid (GABA) was found in higher concentrations in RYGB than that in Sham groups and could play a role in the metabolic benefits associated with RYGB surgery. While no significant difference in urinary BA excretion, RYGB lowered both portal vein and circulating BA compared to Sham groups. These findings provide a valuable resource for how dynamic, multi-systems changes impact on overall metabolic health, and may provide potential therapeutic targets for developing downstream non-surgical treatment for

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