Meera Shanmuganathan

McMaster University | McMaster · Department of Chemistry and Chemical Biology

Background: The role of circulating metabolites on child development is understudied. We investigated associations between children's serum metabolome and early childhood development (ECD). Methods: Untargeted metabolomics was performed on serum samples of 5,004 children aged 6-59 months, a subset of participants from the Brazilian National Survey...

Mass spectrometry (MS)-based metabolomics often rely on separation techniques when analyzing complex biological specimens to improve method resolution, metabolome coverage, quantitative performance, and/or unknown identification. However, low sample throughput and complicated data preprocessing procedures remain major barriers to affordable metabol...

Cellular senescence has been implicated in the aging-related dysfunction of satellite cells, the resident muscle stem cell population primarily responsible for the repair of muscle fibres. Despite being in a state of permanent cell cycle arrest, these cells remain metabolically active and release an abundance of factors that can have detrimental ef...

Mass spectrometry (MS)-based metabolomics often rely on separation techniques when analyzing complex biological specimens to improve method resolution, metabolome coverage, quantitative performance, and/or unknown identification. However, low sample throughput and complicated data pre-processing procedures remain major barriers to affordable metabo...

Background: The role of circulating metabolites on child development is understudied. We investigated associations between children’s serum metabolome and early childhood development (ECD). Methods: Untargeted metabolomics was performed on serum samples of 5,004 children aged 6-59 months, a subset of participants from the Brazilian National Survey...

The human gut microbiome establishes and matures during infancy, and dysregulation at this stage may lead to pathologies later in life. We conducted a multi-omics study comprising three generations of family members to investigate the early development of the gut microbiota. Fecal samples from 200 individuals, including infants (0-12 months old; 55...

The Omega-3 Index (O3I) reflects eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content in erythrocytes. While the O3I is associated with numerous health outcomes, its widespread use is limited. We investigated whether urinary metabolites could be used to non-invasively monitor the O3I in an exploratory analysis of a previous placebo-co...

Damming of a river can trap and elevate levels of sediment-bound elements and alter food web dynamics in created reservoirs. It follows that dams may alter how elements and other nutrients, like the beneficial omega-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are accumulated in fish and thus the chemical comp...

Evidence supports a complex interplay of gut microbiome and host metabolism as regulators of obesity. The metabolic phenotype and microbial metabolism of host diet may also contribute to greater obesity risk in children early in life. This study aimed to identify features that discriminated overweight/obese from normal weight infants by integrating...

Background Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex....

Background: In pregnancy, it is deemed choline is an essential nutrient and carnitine needs are increased but amounts remain undefined. Objective: We aimed to measure choline and total dietary protein and dairy protein intake from food and supplements across pregnancy and the response to intake by profiling choline and carnitine metabolites acro...

Aside from centrally induced trained immunity in the bone marrow (BM) and peripheral blood by parenteral vaccination or infection, evidence indicates that mucosal-resident innate immune memory can develop via a local inflammatory pathway following mucosal exposure. However, whether mucosal-resident innate memory results from integrating distally ge...

Background Diet is known to affect the gut microbiota and the serum metabolome in adults, but this has not been fully explored in infants. Infancy is an important developmental period that may influence a person’s long-term health. Infant development can be affected by diet, that also interacts with the developing gut microbiota. Objective To expl...

Lipidomics aims to comprehensively analyze a diverse range of lipid classes in complex biological samples, including non‐esterified fatty acids and glycerophospholipids. Methods developed for quantitative lipid profiling over the past 70 years have closely mirrored technological advances in analytical instrumentation involving separation science an...

The extent to which variation in food-related metabolites are attributable to non-dietary factors remains unclear, which may explain inconsistent food-metabolite associations observed in population studies. This study examined the association between non-dietary factors and the serum concentrations of food-related biomarkers and quantified the amou...

Cellular senescence is considered a hallmark of aging that often occurs in tissues and cells in response to DNA damage. Most healthy cells become senescent after a fixed number of divisions or irreparable genomic damage, often because of external conditions such as circulating factors that are released by adjacent senescent cells. These secreted fa...

Introduction: This study aimed to identify serum metabolomic signatures associated with gestational diabetes mellitus (GDM), and to examine if ethnic-specific differences exist between South Asian and white European women. Research design and methods: Prospective cohort study with a nested case-control analysis of 600 pregnant women from two Can...

Background Defining the metabolic syndrome (MetS) in children remains challenging. Furthermore, a dichotomous MetS diagnosis can limit the power to study associations. We sought to characterize the serum metabolite signature of the MetS in early childhood using high-throughput metabolomic technologies that allow comprehensive profiling of metabolic...

Diet is known to affect the gut microbiome and metabolome composition in adults, but this has not been fully explored in infants. Dietary patterns from 1 year–old infants (n=182) from the South Asian Birth Cohort (START) study were compared to gut microbiome alpha and beta diversity and to taxa abundance differences. Diet – serum metabolite associa...

Metabolomics offers new insights into disease mechanisms that is enhanced when adopting orthogonal instrumental platforms to expand metabolome coverage, while also reducing false discoveries by independent replication. Herein, we report the first inter-method comparison when using multisegment injection-capillary electrophoresis-mass spectrometry (...

Rates of pediatric Crohn’s disease (CD) and ulcerative colitis (UC) are increasing globally. Differentiation of these inflammatory bowel disease (IBD) subtypes however can be challenging when relying on invasive endoscopic approaches. We sought to identify urinary metabolic signatures of pediatric IBD at diagnosis, and during induction treatment. N...

A standardized data workflow is described for large-scale serum metabolomic studies using multisegment injection-capillary electrophoresis-mass spectrometry. Multiplexed separations increase throughput (<4 min/sample) for quantitative determination of 66 polar/ionic metabolites in serum filtrates consistently detected (coefficient of variance (CV)...

Short-chain fatty acids (SCFAs) and electrolytes are major constituents of human feces involved in maintaining gastrointestinal homeostasis that underlie complex diet, host and microbiome interactions. Reliable quantification of SCFAs and electrolytes is challenging given the heterogeneity of stool specimens from pediatric patients with diarrhea-pr...

Acetylsalicylic acid (ASA), also known as aspirin, appears to be ineffective in inhibiting platelet aggregation in 20–30% of patients. Light transmission aggregometry (LTA) is a gold standard platelet function assay. In this pilot study, we used LTA to personalize ASA therapy ex vivo in atherosclerotic patients. Patients were recruited who were on...

Capillary zone electrophoresis-mass spectrometry (CE-MS) is a mature analytical tool for the efficient profiling of (highly) polar and ionizable compounds. However, the use of CE-MS in comparison to other separation techniques remains underrepresented in metabolomics, as this analytical approach is still perceived as technically challenging and les...

Background: Advances in metabolomics are anticipated to decipher associations between dietary exposures and health. Replication biomarker studies in different populations are critical to demonstrate generalizability. Objectives: To identify and validate robust serum metabolites associated with diet quality and specific foods in a multiethnic coh...

A large body of evidence has linked unhealthy eating patterns with an alarming increase in obesity and chronic disease worldwide. However, existing methods of assessing dietary intake in nutritional epidemiology rely on food frequency questionnaires or dietary records that are prone to bias and selective reporting. Herein, metabolic phenotyping was...

Management of phenylketonuria (PKU) requires lifelong restriction of phenylalanine (Phe) intake using specialized medical foods to prevent neurocognitive impairment in affected patients. However, dietary adherence is challenging to maintain while...

A large body of evidence has linked unhealthy eating with an alarming increase in obesity and chronic disease worldwide. However, existing methods of assessing dietary intake rely on food frequency questionnaires or dietary records that are prone to bias and selective reporting. Herein, metabolic phenotyping was performed on 42 healthy participants...

A large body of evidence has linked unhealthy eating with an alarming increase in obesity and chronic disease worldwide. However, existing methods of assessing dietary intake rely on food frequency questionnaires or dietary records that are prone to bias and selective reporting. Herein, metabolic phenotyping was performed on 42 healthy participants...

Capillary electrophoresis-mass spectrometry (CE-MS) offers a high efficiency microseparation platform for amino acid profiling when analyzing volume-restricted biological samples, such as a dried blood spot punch. Direct analysis of amino acids and their analogs is routinely achieved using strongly acidic buffer conditions under positive-ion mode d...

New analytical methods are urgently needed to enable high-throughput, yet comprehensive drug screening, given an alarming opioid and prescription drug crisis in public health. Conventional urine drug testing based on a two-tier immunoassay screen followed by a gas chromatography-tandem mass spectrometry (GC-MS/MS) or liquid chromatography-tandem ma...

Expanded newborn screening of inborn errors of metabolism (IEM) based on tandem mass spectrometry (MS/MS) technology is one of the most successful preventative healthcare initiatives for presymptomatic diagnosis and treatment of rare yet treatable genetic diseases in the population. However, confirmatory testing of presumptive screen-positive cases...

Urinary 1-hydroxypyrene (OH-Pyr) is widely used for biomonitoring human exposures to polycyclic aromatic hydrocarbons (PAHs) from air pollution and tobacco smoke. However, there have been few rigorous validation studies reported to ensure reliable OH-Pyr determination for occupational health and risk assessment. Herein, we report an inter-laborator...

An investigation of brominated flame retardants (BFRs), polybrominated diphenylethers (PBDEs), and chlorinated flame retardants was conducted in samples from Canadian wastewater treatment plants (WWTPs). The penta-BDE mixture and deca-BDE were most commonly detected. Median removal efficiencies of PBDEs by WWTPs were 71% to 99% and higher concentra...

J. Sep. Sci. 2015, 38, 3262-3270 DOI: 10.1002/jssc.201500551 This cover picture illustrates an inter-laboratory study on the robustness and portability of capillary electrophoresis-mass spectrometry that is presented in this issue. Thirteen independent laboratories located around the globe as indicated on the map were participating in this study. T...

A collaborative study on the robustness and portability of a capillary electrophoresis with mass spectrometry method for peptide mapping was performed by an international team, consisting of 13 independent laboratories from academia and industry. All participants used the same batch of samples, reagents and coated capillaries to run their assays, w...

High quality assays are needed in drug discovery to reduce the high attrition rate of lead compounds during primary screening. Capillary electrophoresis (CE) represents a versatile micro-separation technique for resolution of enzyme-catalyzed reactions, including substrate(s), product(s), cofactor(s) and their stereoisomers, which is needed for rel...

Pharmacological chaperones (PCs) are small molecules that stabilize and promote protein folding. Enzyme inhibition is widely used for PC selection; however, it does not accurately reflect chaperone activity. We introduce a functional assay for characterization of PCs based on their capacity to restore enzyme activity that is abolished upon chemical...

Pharmacological chaperones (PCs) represent a promising therapeutic strategy for treatment of lysosomal storage disorders based on enhanced stabilization and trafficking of mutant protein upon orthosteric and/or allosteric binding. Herein, we introduce a simple yet reliable enzyme assay using capillary electrophoresis (CE) for inhibitor screening of...

Separation and quantification of trans-resveratrol in blueberry extracts were achieved using high performance liquid chromatography (HPLC). Trans-resveratrol in blueberry juice was found to be at a high level of 16.60 ± 0.19 µg/mL. This antioxidant polyphenolic compound was also quantified, in two brands of blueberry powder, to be 236.4 ± 7.5 µg/g...