Jeremy K Nicholson

Jeremy K Nicholson
Murdoch University

BSc PhD DSc (Hon) C.Biol FRSB, C.Chem FRSC FBTS FRCPath FMedSci HonFRCP
Director, Australian National Phenome Centre

About

1,043
Publications
199,548
Reads
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91,189
Citations
Citations since 2016
222 Research Items
37514 Citations
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Introduction
Working at the interface between metabolic discovery chemistry and clinical translation for over 30 years, we investigate systemic effects of disease and recovery processes in patients using integrative systems biology methods. COVID-19 is a good exemplar. We developed new analytical techniques to measure COVID induced inflammation and new metabolic frameworks for assessment of systemic recovery and enhanced biomarkers to asses long-term cardiometabolic and neurological effects of the disease.
Additional affiliations
October 2018 - present
Murdoch University
Position
  • Managing Director
October 2018 - December 2025
Imperial College London
Position
  • Professor Emeritus
July 2016 - present
University of Western Australia
Position
  • Professor
Description
  • Adjunct (Honorary) Position

Publications

Publications (1,043)
Article
The metabolic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on human blood plasma were characterized using multiplatform metabolic phenotyping with nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS). Quantitative measurements of lipoprotein subfractions, α-1-acid gly...
Article
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We performed quantitative metabolic phenotyping of blood plasma in parallel with cytokine/chemokine analysis from participants who were either SARS-CoV-2 (+) (n = 10) or SARS-CoV-2 (-) (n = 49). SARS-CoV-2 positivity was associated with a unique metabolic phenotype and demonstrated a complex systemic response to infection, including severe perturba...
Article
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We present a multivariate metabotyping approach to assess the functional recovery of nonhospitalized COVID-19 patients and the possible biochemical sequelae of “Post-Acute COVID-19 Syndrome”, colloquially known as long-COVID. Blood samples were taken from patients ca. 3 months after acute COVID-19 infection with further assessment of symptoms at 6...
Preprint
Full-text available
The biology driving individual patient responses to SARS-CoV-2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data, covering a year post disease onset, from 215 SARS-CoV-2 infected subjects with differing disease severities. Our analyses revealed distinct “systemic recov...
Article
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To gain insight into the complex microbiome-gut-brain axis in irritable bowel syndrome (IBS), several modalities of biological and clinical data must be combined. We aimed to identify profiles of fecal microbiota and metabolites associated with IBS and to delineate specific phenotypes of IBS that represent potential pathophysiological mechanisms. F...
Article
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The hydrolysis of xenobiotic glucuronides by gut bacterial glucuronidases reactivates previously detoxified compounds resulting in severe gut toxicity for the host. Selective bacterial β-glucuronidase inhibitors can mitigate this toxicity but their impact on wider host metabolic processes has not been studied. To investigate this the inhibitor 4-(8...
Article
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Background Production of SCFAs from food is a complex and dynamic saccharolytic fermentation process mediated by both human and gut microbial factors. Knowledge of SCFA production and of the relation between SCFA profiles and dietary patterns is lacking. Objectives Temporal changes in SCFA concentrations in response to 2 contrasting diets were inv...
Article
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The evolution of complex in vitro models of the human gastrointestinal system to interrogate the biochemical functionality of the gut microbiome has augmented our understanding of its role in human physiology and pathology. With 5718 authors from 52 countries, gut bioreactor research reflects the growing awareness of our need to understand the cont...
Article
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Background Surgical debridement is a necessary procedure for burn patients that require the removal of eschar. The extent of debridement is currently guided by clinical judgement, with excess debridement of healthy tissue potentially leading to excessive scar, or inadequate debridement increasing risk of infection. Thus, an objective real-time meas...
Article
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A JEDI NMR pulse experiment incorporating relaxational, diffusional and J-modulation peak editing has been implemented for a low field (80 MHz proton resonance frequency) spectrometer system to measure quantitatively two recently discovered plasma markers of SARS-CoV-2 infection and general inflammation. JEDI spectra capture a unique signature of t...
Article
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A growing body of evidence supports the concept of a systemic response to non-severe thermal trauma. This provokes an immunosuppressed state that predisposes paediatric patients to poor recovery and increased risk of secondary morbidity. In this study, to understand the long-term systemic effects of non-severe burns in children, targeted mass spect...
Article
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Objective Men are at greater risk from COVID-19 than women. Older, overweight men, and those with type 2 diabetes, have lower testosterone concentrations, and poorer COVID-19-related outcomes. We analysed associations of premorbid serum testosterone concentrations, not confounded by effects of acute SARS-CoV-2 infection, with COVID-19-related morta...
Cover Page
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Special metabolic Edition
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SARS-CoV-2 infection causes a significant reduction in lipoprotein-bound serum phospholipids give rise to supra-molecular phospholipid composite (SPC) signals observed in diffusion and relaxation edited 1 H NMR spectra. To characterize the chemical structural components and compartmental location of SPC and to understand further its possible diagno...
Article
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Trimethylamine (TMA) and its N-oxide (TMAO) are ubiquitous in prokaryote and eukaryote organisms as well as in the environment, reflecting their fundamental importance in evolutionary biology, and their diverse biochemical functions. Both metabolites have multiple biological roles including cell-signaling. Much attention has focused on the signific...
Article
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Proton nuclear magnetic resonance (NMR) N-acetyl signals (Glyc) from glycoproteins and supramolecular phospholipids composite peak (SPC) from phospholipid quaternary nitrogen methyls in subcompartments of lipoprotein particles) can give important systemic metabolic information, but their absolute quantification is compromised by overlap with interf...
Article
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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, con...
Article
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SARS COV-2 infection causes acute and frequently severe respiratory disease with associated multi-organ damage and systemic disturbances in many biochemical pathways. Metabolic phenotyping provides deep insights into the complex immunopathological problems that drive the resulting COVID-19 disease and is also a source of novel metrics for assessing...
Article
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Improved methods are required for investigating the systemic metabolic effects of SARS-CoV-2 infection and patient stratification for precision treatment. We aimed to develop an effective method using lipid profiles for discriminating between SARS-CoV-2 infection, healthy controls, and non-SARS-CoV-2 respiratory infections. Targeted liquid chromato...
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Significance While the effects of gut microbes on brain development and function have been described, the mechanisms remain largely unknown. Here, we report that tryptophan-metabolizing gut microbes secrete indoles that regulate neurogenesis in the adult hippocampus. This stimulatory effect on adult neurogenesis is mediated by the metabolic- and im...
Conference Paper
Background: Tumor-derived Extracellular Vesicles (EVs) are found in body fluids of cancer patients. These EVs include exosomes and microvesicles, which play an important role in tumor development and metastasis. Although EVs have great potential as liquid biopsies for early detection of breast cancer, the lipid composition of breast cancer-derived...
Article
Metabolic phenotyping is an important tool in translational biomedical research. The advanced analytical technologies commonly used for phenotyping, including mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy, generate complex data requiring tailored statistical analysis methods. Detailed protocols have been published for dat...
Article
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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...
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Objective Gut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health. Design In 271 middle-aged non-diabetic Danish individuals, who were stratified on...
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Background The gut microbiome and iron status are known to play a role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear. Results Here, we applied an integrative systems medicine approach (faecal metagenomics, plasma and urine metabolomics, hepatic transcriptomics) in 2 well-cha...
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The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8⁺ T cell im...
Article
The application of metabolomics in translational research suffers from several technological bottlenecks, such as data reproducibility issues and the lack of standardization of sample profiling procedures. Here, we report an automated high-throughput metabolite array technology that can rapidly and quantitatively determine 324 metabolites including...
Article
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We have applied nuclear magnetic resonance spectroscopy based plasma phenotyping to reveal diagnostic molecular signatures of SARS-CoV-2 infection via combined diffusional and relaxation editing (DIRE). We compared plasma from healthy age-matched controls (n = 26) with SARS-CoV-2 negative non-hospitalized respiratory patients and hospitalized respi...
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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:...
Article
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The utility of low sample volume in vitro diagnostic (IVDr) proton nuclear magnetic resonance (¹H NMR) spectroscopic experiments on blood plasma for information recovery from limited availability or high value samples was exemplified using plasma from patients with SARS-CoV-2 infection and normal controls. ¹H NMR spectra were obtained using solvent...
Article
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The incidence of neuroendocrine neoplasms (NEN) is increasing, but established biomarkers have poor diagnostic and prognostic accuracy. Here, we aim to define the systemic metabolic consequences of NEN and to establish the diagnostic utility of proton nuclear magnetic resonance spectroscopy (1H-NMR) for NEN in a prospective cohort of patients throu...
Preprint
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In a study of 207 SARS-CoV2-infected individuals with a range of severities followed over 12 weeks from symptom onset, we demonstrate that an early robust immune response, without systemic inflammation, is characteristic of asymptomatic or mild disease. Those presenting to hospital had delayed adaptive responses and systemic inflammation already ev...
Article
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To investigate the systemic metabolic effects of SARS-CoV-2 infection, we analyzed 1 H NMR spectroscopic data on human blood plasma and co-modeled with multiple plasma cytokines and chemokines (measured in parallel). Thus, 600 MHz 1 H solvent-suppressed single-pulse, spin-echo, and 2D J-resolved spectra were collected on plasma recorded from SARS-C...
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Finding early disease markers using non-invasive and widely available methods is essential to develop a successful therapy for Alzheimer’s Disease. Few studies to date have examined urine, the most readily available biofluid. Here we report the largest study to date using comprehensive metabolic phenotyping platforms (NMR spectroscopy and UHPLC-MS)...
Article
Tyrosine plays a key role in mammalian biochemistry and defects in its metabolism (e.g., tyrosinemia, alkaptonuria etc.) have significant adverse consequences for those affected if left untreated. In addition, gut bacterially-derived p-cresol and its metabolites are of interest as a result of various effects on host xenobiotic metabolism. A fit-for...
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Validation of a QTof vs QQQ-MS method for quantitative and exploratory amino acid and biogenic amine measurement in serum/plasma and application to study effects of SARS-CoV-2 infection.
Article
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Quantitative nuclear magnetic resonance (NMR) spectroscopy of blood plasma is widely used to investigate perturbed metabolic processes in human diseases. The reliability of biochemical data derived from these measurements is dependent on the quality of the sample collection and exact preparation and analysis protocols. Here, we describe systematica...
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Motivation: Large-scale population omics data can provide insight into associations between gene-environment interactions and disease. However, existing dimension reduction modelling techniques are often inefficient for extracting detailed information from these complex datasets. Results: Here we present an interactive software pipeline for expl...
Article
Metabolic profiling of biological samples provides important insights into multiple physiological and pathological processes but is hindered by a lack of automated annotation and standardized methods for structure elucidation of candidate disease biomarkers. Here we describe a system for identifying molecular species derived from nuclear magnetic r...
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Dietary assessment traditionally relies on self-reported data, which are often inaccurate and may result in erroneous diet–disease risk associations. We illustrate how urinary metabolic phenotyping can be used as an alternative approach to obtain information on dietary patterns. We used two multipass 24 h dietary recalls, obtained on two occasions...
Article
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A rapid reversed-phase gradient method employing a 50 mm × 1 mm i.d., C18 microbore column, combined with ion mobility and high-resolution mass spectrometry, was applied to the metabolic phenotyping of urine samples obtained from rats receiving different diets. This method was directly compared to a “conventional” method employing a 150 × 2.1 mm i....
Article
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Oncogenic transformation is associated with profound changes in cellular metabolism, but whether tracking these can improve disease stratification or influence therapy decision-making is largely unknown. Using the iKnife to sample the aerosol of cauterized specimens, we demonstrate a new mode of real-time diagnosis, coupling metabolic phenotype to...
Article
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Habitual consumption of poor quality diets is linked directly to risk factors for many non-communicable diseases. This has resulted in the vast majority of countries and the World Health Organization developing policies for healthy eating to reduce the prevalence of non-communicable diseases in the population. However, there is mounting evidence of...
Article
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Methotrexate (MTX) is a chemotherapeutic agent that can cause a range of toxic side effects including gastrointestinal damage, hepatotoxicity, myelosuppression, and nephrotoxicity and has potentially complex interactions with the gut microbiome. Following untargeted UPLC-qtof-MS analysis of urine and fecal samples from male Sprague Dawley rats (N =...