Elaine Holmes

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Verified

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• BSc, PhD
• Head of Centre at Murdoch University

We report the successful development and trans- lation of high-field nuclear magnetic resonance (NMR) based comprehensive lipoprotein analysis to routine benchtop systems. This demonstrates the potential to reimagine population level cardiovascular disease risk analysis and individual level screening based on blood sampling. Using a quantitative ca...

COVID-19 vaccines are crucial in reducing SARS-CoV-2 transmission and severe health outcomes. Despite widespread administration, their long-term systemic effects on human metabolism remain inadequately understood. This longitudinal study aims to evaluate IgG responses, 34 cytokines, 112 lipoproteins, and 21 low-molecular-weight metabolites in 33 in...

Dried blood spot (DBS) sample collections can offer a minimally invasive, cost-effective alternative to traditional venepuncture for remote sampling and high-frequency metabolic profiling. We present an optimized protocol for DBS-based extraction and comprehensive untargeted 4D lipid profiling using ultrahigh-performance liquid chromatography coupl...

Understanding the distribution and variation in inflammatory markers is crucial for advancing our knowledge of inflammatory processes and evaluating their clinical utility in diagnosing and monitoring acute and chronic disease. ¹H NMR spectroscopy of blood plasma and serum was applied to measure a composite panel of inflammatory markers based on ac...

Dried blood spot (DBS) sample collections can offer a minimally invasive, cost-effective alternative to traditional venepuncture for remote sampling and high-frequency metabolic profiling. We present an optimised protocol for DBS-based extraction and comprehensive untargeted 4D lipid profiling using ultrahigh-performance liquid chromatography coupl...

Background Epidemiologic evidence linking blood pressure (BP) and body weight-lowering effects with fruit and vegetable consumption mostly relies on self-reported dietary assessment prone to misreport and under- or overestimation of relationships. Objectives We aimed to characterize objective 24-h urinary metabolites and a derived metabolite score...

Motivation Metabolic phenotyping, using high-resolution spectroscopic molecular fingerprints of biological samples, has demonstrated diagnostic, prognostic, and mechanistic value in clinical studies. However, clinical translation is hindered by the lack of viable workflows and challenges in converting spectral data into usable information. Results...

As part of a strategy for accommodating missing data in large heterogeneous datasets, two Random Forest-based (RF) imputation methods, missForest and MICE were evaluated along with several strategies to help them handle the inherent structure of the dataset. Background: A total of 3817 complete cases of clinical chemistry variables from a large-sca...

Whilst wound repair in severe burns has received substantial research attention, non-severe burns (<20 % total body surface area) remain relatively understudied, despite causing considerable physiological impact and constituting most of the hospital admissions for burns. Early prediction of healing outcomes would decrease financial and patient burd...

The evidence on the impact of fruits and vegetable types on cardiovascular risk factors remains limited. Specifically, the utilisation of biomarkers to objectively measure dietary compliance and metabolic responses is emerging. This protocol and baseline characteristics of a pilot randomised controlled, crossover, dietary intervention study aimed t...

Dietary interventions to combat non-communicable diseases focus on optimising food intake but overlook the influence of food structure. Food processing often causes the loss of foodstructure, but how this influences human gastrointestinal digestion and the signals it generates, such as gut hormones that affect homeostatic mechanisms is unclear. In...

The human ileum contains a high density of enteroendocrine L-cells, which release the appetite-suppressing hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in response to food intake. Recent evidence highlighted the potential role of food structures in PYY release, but the link between food structures, ileal metabolites,...

Context The role of glucagon-like peptide-1(GLP-1) in Type 2 diabetes (T2D) and obesity is not fully understood. Objective We investigate the association of cardiometabolic, diet and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D. Method We analysed cross-sectional data from the two Innovative Med...

Understanding the intricate ecological interactions within the gut microbiome and unravelling its impact on human health is a challenging task. Bioreactors are valuable tools that have contributed to our understanding of gut microbial ecology. However, there is a lack of studies describing and comparing the microbial diversity cultivated in these m...

Gut microbes supporting body growth are known but the mechanisms are less well documented. Using the microbial tryptophan metabolite indole, known to regulate prokaryotic cell division and metabolic stress conditions, we mono-colonized germ-free (GF) mice with indole-producing wild-type Escherichia coli (E. coli) or tryptophanase-encoding tnaA knoc...

Inulin, a polysaccharide characterized by a β-2,1 fructosyl-fructose structure terminating in a glucosyl moiety, is naturally present in plant roots and tubers. Current methods provide average degrees of polymerization (DP) but lack information on the distribution and absolute concentration of each DP. To address this limitation, a reproducible (CV...

Delayed diagnosis of patients with sepsis or septic shock is associated with increased mortality and morbidity. UPLC-MS and NMR spectroscopy were used to measure panels of lipoproteins, lipids, biogenic amines, amino acids, and tryptophan pathway metabolites in blood plasma samples collected from 152 patients after admission to the Intensive Care U...

To ensure biological validity in metabolic phenotyping, findings must be replicated in independent sample sets. Targeted workflows have long been heralded as ideal platforms for such validation due to their robust quantitative capability. We evaluated the capability of liquid chromatography-mass spectrometry (LC-MS) assays targeting organic acids a...

We investigated plasma and serum blood derivatives from capillary blood microsamples (500 μL, MiniCollect tubes) and corresponding venous blood (10 mL vacutainers). Samples from 20 healthy participants were analyzed by 1 H NMR, and 112 lipoprotein subfraction parameters; 3 supramolecular phospholipid composite (SPC) parameters from SPC 1 , SPC 2 ,...

We present compelling evidence for the existence of an extended innate viperin-dependent pathway, which provides crucial evidence for an adaptive response to viral agents, such as SARS-CoV-2. We show the in vivo biosynthesis of a family of novel endogenous cytosine metabolites with potential antiviral activities. Two-dimensional nuclear magnetic re...

The rising prevalence of obesity in Saudi Arabia is a major contributor to the nation’s high levels of cardiometabolic diseases such as type 2 diabetes. To assess the impact of obesity on the diabetic metabolic phenotype presented in young Saudi Arabian adults, participants (n = 289, aged 18–40 years) were recruited and stratified into four groups:...

Background A common misconception about ageing is that a decline in brain health is solely observed in those who have dementia. In fact, decreases in cognitive function and reductions in brain volume are commonly observed in adults over the age of 65. Brain changes in older adulthood have been shown to be decreased in individuals who are more physi...

Minimally-invasive capillary blood sampling is functionally equivalent and cross-validated to venous lipoproteins measurement and cardiovascular risk assessment. This paves the way large scale prospective risk assessment including remote locations with limited medical personnel resources.

Rationale Evidence suggests consumption of a Mediterranean diet (MD) can positively impact both maternal and offspring health, potentially mediated by a beneficial effect on inflammatory pathways. We aimed to apply metabolic profiling of serum and urine samples to assess differences between women who were stratified into high and low alignment to a...

Globally, burns are a significant cause of injury that can cause substantial acute trauma as well as lead to increased incidence of chronic comorbidity and disease. To date, research has primarily focused on the systemic response to severe injury, with little in the literature reported on the impact of nonsevere injuries (<15% total burn surface ar...

We investigated plasma and serum blood derivatives from capillary blood microsamples (500 μL, MiniCollect® tubes) and corresponding venous blood (10 mL vacutainers). Samples from twenty healthy participants were analysed by 1H-NMR and 112 lipoprotein subfraction parameters; 3 supramolecular phospholipid composite (SPC) parameters from SPC1, SPC2, a...

NMR spectroscopy is a mainstay of metabolic profiling approaches to investigation of physiological and pathological processes. The one‐dimensional proton pulse sequences typically used in phenotyping large numbers of samples generate spectra that are rich in information but where metabolite identification is often compromised by peak overlap. Recen...

Childhood mental disorders, including emotional and behavioural problems (EBP) are increasingly prevalent. Higher maternal oxidative stress (OS) during pregnancy (matOSpreg) is linked to offspring mental disorders. Environmental factors contribute to matOSpreg. However, the role of matOSpreg in childhood EBP is unclear. We investigated the associat...

Background It is estimated that 10% of patients that suffered from severe acute SARS-CoV-2 infection experience symptoms beyond 3 months post-disease onset. Long COVID is a multisystemic condition that comprises more than 200 symptoms. Common new-onset medical conditions include cardiovascular, type-2 diabetes and chronic fatigue syndrome. Whilst p...

Background Metabolic phenotyping is an established tool in systems medicine that captures a profile of one’s individual health status and reflects the interaction between genes and external stressors. It uses analytical platforms such as NMR or MS to acquire molecular profiles, and modelling to extract actionable knowledge. Applying these technique...

The microbiome has emerged as a key determinant of human health and reproduction, with recent evidence suggesting a dysbiotic microbiome is implicated in adverse perinatal health outcomes. The existing research has been limited by the sample collection and timing, cohort design, sample design, and lack of data on the preconception microbiome. This...

It has been established that the human gut microbiota is central to health, and, consequently, there has been a growing desire to positively modulate its composition and/or function through, for example, the use of fermented foods, prebiotics or probiotics. Here, we compare the relative impact of the daily consumption of an inulin-enriched diet (n...

Inulin, a β-2,1 fructosyl-fructose polysaccharide terminating with a glucosyl moiety, occurs naturally in plant roots/tubers. The chain length of inulin affects gut microbiota compositions and may potentially modulate chronic diseases. Current methods for inulin measurement rely on average degrees of polymerization (DP), lacking distribution and ab...

Whilst wound repair in severe burns has received substantial research attention, non-severe burns (<20% total body surface area) remain relatively understudied, despite causing considerable physiological impact and constituting most of the hospital admissions for burns. Early prediction of healing outcomes would decrease financial and patient burde...

An integrative multi-modal metabolic phenotyping model was developed to assess the systemic plasma sequelae of SARS-CoV-2 (rRT-PCR positive) induced COVID-19 disease in patients with different respiratory severity levels. Plasma samples from 306 unvaccinated COVID-19 patients were collected in 2020 and classified into four levels of severity rangin...

Dried blood spots (DBSs) are a minimally invasive and cost-effective method for collecting and storing blood samples for metabolic phenotyping research that can enhance our understanding of human metabolism and lead to development of personalised interventions that improve patient outcomes. This is because DBSs allow for more frequent and longitudi...

Background: Circulating lipids and lipoproteins mediate cardiovascular risk, however routine plasma lipid biochemistry provides limited information on pro-atherogenic remnant particles. Objective: We analysed plasma lipoprotein subclasses including very low-density and intermediate-density lipoprotein (VLDL and IDL); and assessed their associati...

Introduction Burn injury in children causes prolonged systemic effects on physiology and metabolism leading to increased morbidity and mortality, yet much remains undefined regarding the metabolic trajectory towards specific health outcomes. Methods A multi-platform strategy was implemented to evaluate the long-term immuno-metabolic consequences o...

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with ursodeoxycholic acid (UDCA) as first-line treatment. Poor response to UDCA is associated with a higher risk of progressing to cirrhosis, but the underlying mechanisms are unclear. UDCA modulates the composition of primary and bacterial-derived bile acids (BAs). We charact...

We present compelling evidence for the existence of an evolutionary adaptive response to viral agents such as SARS-CoV-2, that results in the human in vivo biosynthesis of a family of compounds with potential antiviral activity. Using nuclear magnetic resonance (NMR) spectroscopy, we detected a characteristic spin-system motif indicative of the pre...

Globally, burns are a significant cause of injury that can cause substantial acute trauma as well as lead to increased incidence of chronic co-morbidity and disease. To date, research has primarily focused on the systemic response to severe injury, with little in the literature reported on impact of non-severe injuries (<15% total burn surface area...

Since the early 1980s, multiple researchers have contributed to the development of in vitro models of the human gastrointestinal system for the mechanistic interrogation of the gut microbiome ecology. Using a bioreactor for simulating all the features and conditions of the gastrointestinal system is a massive challenge. Some conditions, such as tem...

Dysregulated lipid metabolism underpins many chronic diseases including cardiometabolic diseases. Mass spectrometry-based lipidomics is an important tool for understanding mechanisms of lipid dysfunction and is widely applied in epidemiology and clinical studies. With ever-increasing sample numbers, single batch acquisition is often unfeasible, req...

It has been established that the human gut microbiota is central to health, and, consequently, there has been a growing desire to positively modulate its composition and/or function through, for example, the use of fermented foods, prebiotics or probiotics. Here, we compare the relative impact of the daily consumption of an inulin-enriched diet, a...

The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses...

To investigate the underlying molecular mechanisms on how the gut microbe metabolite, indoles, regulate host organ growth and function, germ-free male mice were mono-colonized with indole-producing wildtype Escherichia coli or tryptophanase-encoding tnaA knockout mutant indole-non-producing E. coli . The indole mutant E. coli recipient mice exhibit...

The human metabolic profile is affected by host genetic, microbiome, environmental/lifestyle, and dietary factors which may all influence human raised blood pressure (BP). We aim to delineate metabolite-BP relationships by evaluating the effect of single-nucleotide polymorphisms (SNPs) mapped to enzyme-coding genes involved in metabolic pathways on...

Free-range eggs are ethically desirable but as with all high-value commercial products, the establishment of provenance can be problematic. Here, we compared a simple one-step isopropanol method to a two-step methyl-tert-butyl ether method for extracting lipid species in chicken egg yolks before LC-MS/MS analysis. The isopropanol method extracted 9...

Background and Aims Acute liver failure (ALF) is a life-threatening disease characterised by high-grade inflammation and immunoparesis with a high incidence of death from sepsis. Here, we aimed to describe the metabolic dysregulation in ALF and determine whether systemic immune responses are modulated via the lysophosphatidylcholine(LPC)-autotaxin(...

Background/Objectives Global liquid chromatography mass spectrometry (LC-MS) profiling in a Thai population identified a urinary metabolic signature in Opisthorchis viverrini-induced cholangiocarcinoma (CCA), primarily characterised by disturbance in acylcarnitine, bile acid, steroid and purine metabolism. However, the detection of thousands of analy...

Genome-wide association studies (GWASs) have identified genetic loci associated with the risk of Alzheimer’s disease (AD), but the molecular mechanisms by which they confer risk are largely unknown. We conducted a metabolome-wide association study (MWAS) of AD-associated loci from GWASs using untargeted metabolic profiling (metabolomics) by ultrape...

Cholestatic liver disease patients, including those with primary biliary cholangitis, can experience symptoms of impaired cognition or "brain fog". This phenomenon remains unexplained and is currently untreatable. Bile duct ligation (BDL) is an established rodent model of cholestasis. In addition to liver changes, BDL animals develop cognitive symp...

Background Resolution of type 2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass. However, the underlying mechanisms have not been fully elucidated. Methods To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity ± T2D ( n = 80, T2D = 42) with part...

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...

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...

One of the most recognisable features of ageing is a decline in brain health and cognitive dysfunction, which is associated with perturbations to regular lipid homeostasis. Although ageing is the largest risk factor for several neurodegenerative diseases such as dementia, a loss in cognitive function is commonly observed in adults over the age of 6...

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...

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...

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...

Industrial production of synthetic nitrogen fertilizers and their crop application have caused considerable environmental impacts. Some eco-friendly alternatives try to solve them but raise some restrictions. We tested a novel method to produce a nitrogen bioinoculant by enriching a soil microbial community in bioreactors supplying N2 by air pumpin...

Broad-spectrum antimicrobial use during the treatment of critical illness influences gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary to secondary bile acids. We previously observed reduced fermentation capacity in the faecal microbiota of critically ill children upon hospital...

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...

This review aims to develop an appropriate review tool for systematically collating metabolites that are dysregulated in disease and applies the method to identify novel diagnostic biomarkers for hepatocellular carcinoma (HCC). Studies that analysed metabolites in blood or urine samples where HCC was compared with comparison groups (healthy, pre-ci...

Background Global liquid chromatography mass spectrometry (LC-MS) profiling in a Thai population identified a urinary metabolic signature in Opisthorchis viverrini-induced cholangiocarcinoma (CCA), primarily characterised by disturbance in acylcarnitine, bile acid, steroid and purine metabolism. However, the detection of thousands of analytes by LC...

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...

Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogen...

Background Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet enhances potassium intake and reduces sodium intake and blood pressure (BP), but the underlying metabolic pathways are unclear. Objective Among free-living populations, delineate metabolic signatures associated with the DASH diet adherence, 24-hr urinary sodium and pot...

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...

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...