Publications by authors named "Rikeish R Muralitharan"

6 Publications

  • Page 1 of 1

A single-center pilot study in Malaysia on the clinical utility of whole-exome sequencing for inborn errors of immunity.

Clin Exp Immunol 2021 Jun 1. Epub 2021 Jun 1.

Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.

Primary immunodeficiency diseases refer to inborn errors of immunity (IEI) that affect the normal development and function of the immune system. The phenotypical and genetic heterogeneity of IEI have made their diagnosis challenging. Hence, whole-exome sequencing (WES) was employed in this pilot study to identify the genetic etiology of 30 pediatric patients clinically diagnosed with IEI. The potential causative variants identified by WES were validated using Sanger sequencing. Genetic diagnosis was attained in 46.7% (14 of 30) of the patients and categorized into autoinflammatory disorders (n = 3), diseases of immune dysregulation (n = 3), defects in intrinsic and innate immunity (n = 3), predominantly antibody deficiencies (n = 2), combined immunodeficiencies with associated and syndromic features (n = 2) and immunodeficiencies affecting cellular and humoral immunity (n = 1). Of the 15 genetic variants identified, two were novel variants. Genetic findings differed from the provisional clinical diagnoses in seven cases (50.0%). This study showed that WES enhances the capacity to diagnose IEI, allowing more patients to receive appropriate therapy and disease management.
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http://dx.doi.org/10.1111/cei.13626DOI Listing
June 2021

Renal ACE2 (Angiotensin-Converting Enzyme 2) Expression Is Modulated by Dietary Fiber Intake, Gut Microbiota, and Their Metabolites.

Hypertension 2021 Jun 19;77(6):e53-e55. Epub 2021 Apr 19.

Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science (R.R.M., E.D., M.N., H.A.J., F.Z.M.), Monash University, Melbourne, Australia.

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17039DOI Listing
June 2021

The conundrum of the gut microbiome and blood pressure: the importance of studying sex and ethnicity.

Eur Heart J 2020 11;41(44):4268-4270

Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science, Monash University, Melbourne, Australia.

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http://dx.doi.org/10.1093/eurheartj/ehaa760DOI Listing
November 2020

Microbial Peer Pressure: The Role of the Gut Microbiota in Hypertension and Its Complications.

Hypertension 2020 12 5;76(6):1674-1687. Epub 2020 Oct 5.

From the Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science (R.R.M., H.A.J., L.X., A.P., F.Z.M.), Monash University, Melbourne, Australia.

There is increasing evidence of the influence of the gut microbiota on hypertension and its complications, such as chronic kidney disease, stroke, heart failure, and myocardial infarction. This is not surprising considering that the most common risk factors for hypertension, such as age, sex, medication, and diet, can also impact the gut microbiota. For example, sodium and fermentable fiber have been studied in relation to both hypertension and the gut microbiota. By combining second- and, now, third-generation sequencing with metabolomics approaches, metabolites, such as short-chain fatty acids and trimethylamine N-oxide, and their producers, have been identified and are now known to affect host physiology and the cardiovascular system. The receptors that bind these metabolites have also been explored with positive findings-examples include known short-chain fatty acid receptors, such as G-protein coupled receptors GPR41, GPR43, GPR109a, and OLF78 in mice. GPR41 and OLF78 have been shown to have inverse roles in blood pressure regulation, whereas GPR43 and GPR109A have to date been demonstrated to impact cardiac function. New treatment options in the form of prebiotics (eg, dietary fiber), probiotics (eg, spp.), and postbiotics (eg, the short-chain fatty acids acetate, propionate, and butyrate) have all been demonstrated to be beneficial in lowering blood pressure in animal models, but the underlying mechanisms remain poorly understood and translation to hypertensive patients is still lacking. Here, we review the evidence for the role of the gut microbiota in hypertension, its risk factors, and cardiorenal complications and identify future directions for this exciting and fast-evolving field.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14473DOI Listing
December 2020

Diet-related gut microbial metabolites and sensing in hypertension.

J Hum Hypertens 2021 Feb 30;35(2):162-169. Epub 2020 Jul 30.

Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science, Monash University, Melbourne, VIC, Australia.

Advances in sequencing technology have increased our understanding of the composition of the gut microbiota and their contribution to health and disease states, including in cardiovascular diseases such as hypertension. The gut microbiota is heavily influenced by diet and produce metabolites such as short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO) from various food sources. SCFAs, such as acetate, propionate, and butyrate, have been shown to have blood pressure, cardiac hypertrophy, and fibrosis lowering properties, while TMAO has been associated with increased risk of major cardiovascular adverse events and mortality. Some of these metabolites have known ligands (for example, SCFA receptors such as GPR41, GPR43, GPR109a, and Olf78 in mice/OR51E2 in humans) which could potentially be manipulated as therapeutic targets for hypertension. In this review, we discuss several types of diet-related gut microbial metabolites and their sensing mechanisms that are relevant for hypertension, and the future directions for the field.
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http://dx.doi.org/10.1038/s41371-020-0388-3DOI Listing
February 2021

Guidelines for Transparency on Gut Microbiome Studies in Essential and Experimental Hypertension.

Hypertension 2019 12 4;74(6):1279-1293. Epub 2019 Nov 4.

Infection and Immunity Program, Monash Biomedicine Discovery Institute (C.R.M.), Monash University, Melbourne, Australia.

Hypertension is a complex and modifiable condition in which environmental factors contribute to both onset and progression. Recent evidence has accumulated for roles of diet and the gut microbiome as environmental factors in blood pressure regulation. However, this is complex because gut microbiomes are a unique feature of each individual reflecting that individual's developmental and environmental history creating caveats for both experimental models and human studies. Here, we describe guidelines for conducting gut microbiome studies in experimental and clinical hypertension. We provide a complete guide for authors on proper design, analyses, and reporting of gut microbiota/microbiome and metabolite studies and checklists that can be used by reviewers and editors to support robust reporting and interpretation. We discuss factors that modulate the gut microbiota in animal (eg, cohort, controls, diet, developmental age, housing, sex, and models used) and human studies (eg, blood pressure measurement and medication, body mass index, demographic characteristics including age, cultural identification, living structure, sex and socioeconomic environment, and exclusion criteria). We also provide best practice advice on sampling, storage of fecal/cecal samples, DNA extraction, sequencing methods (including metagenomics and 16S rRNA), and computational analyses. Finally, we discuss the measurement of short-chain fatty acids, metabolites produced by the gut microbiota, and interpretation of data. These guidelines should support better transparency, reproducibility, and translation of findings in the field of gut microbiota/microbiome in hypertension and cardiovascular disease.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13079DOI Listing
December 2019
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