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    Olfaction in the kidney: 'smelling' gut microbial metabolites.
    Exp Physiol 2016 Apr 27;101(4):478-81. Epub 2015 Aug 27.
    Johns Hopkins University School of Medicine, Baltimore, MD, USA.
    New Findings: What is the topic of this review? This review covers recent findings highlighting roles for renal and vascular sensory receptors that modify blood pressure control in response to changes in gut microbial metabolites. What advances does it highlight? This review highlights the novel roles that G-protein-coupled receptor 41 and olfactory receptor 78 play in blood pressure regulation. The gut microbiota have recently been recognized as an important component of host physiology and pathophysiology. Our recent studies have shown that a subset of gut microbial metabolites, known as short-chain fatty acids, act as ligands for host G-protein-coupled receptors (G-protein-coupled receptor 41 and olfactory receptor 78). Short-chain fatty acid-mediated activation of G-protein-coupled receptor 41 and olfactory receptor 78 modulates blood pressure control, both by modulating renin secretion and by modulating vascular tone directly. Further studies are needed in order to gain a better understanding of the underlying mechanism by which microbiota and microbial metabolites modulate host physiology and their potential implications in health and disease.

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    A novel SCFA receptor, the microbiota, and blood pressure regulation.
    Gut Microbes 2014 Mar-Apr;5(2):202-7. Epub 2013 Dec 20.
    Department of Physiology; Johns Hopkins University School of Medicine; Baltimore, MD USA.
    The maintenance of blood pressure homeostasis is a complex process which is carefully regulated by a variety of inputs. We recently identified two sensory receptors (Olfactory receptor 78 and G protein couple receptor 41) as novel regulators of blood pressure. Both Olfr78 and Gpr41 are receptors for short chain fatty acids (SCFAs), and we showed that propionate (a SCFA) modifies blood pressure in a manner which is differentially modulated by the absence of either Olfr78 or Gpr41. Read More
    Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation.
    Nutrients 2015 Apr 14;7(4):2839-49. Epub 2015 Apr 14.
    Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo 183-8509, Japan.
    During feeding, the gut microbiota contributes to the host energy acquisition and metabolic regulation thereby influencing the development of metabolic disorders such as obesity and diabetes. Short-chain fatty acids (SCFAs) such as acetate, butyrate, and propionate, which are produced by gut microbial fermentation of dietary fiber, are recognized as essential host energy sources and act as signal transduction molecules via G-protein coupled receptors (FFAR2, FFAR3, OLFR78, GPR109A) and as epigenetic regulators of gene expression by the inhibition of histone deacetylase (HDAC). Recent evidence suggests that dietary fiber and the gut microbial-derived SCFAs exert multiple beneficial effects on the host energy metabolism not only by improving the intestinal environment, but also by directly affecting various host peripheral tissues. Read More
    From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites.
    Cell 2016 Jun;165(6):1332-45
    Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 413 45 Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, 2200 København, Denmark. Electronic address:
    A compelling set of links between the composition of the gut microbiota, the host diet, and host physiology has emerged. Do these links reflect cause-and-effect relationships, and what might be their mechanistic basis? A growing body of work implicates microbially produced metabolites as crucial executors of diet-based microbial influence on the host. Here, we will review data supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs). Read More
    Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions.
    Genome Med 2016 Apr 21;8(1):46. Epub 2016 Apr 21.
    Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA.
    Mass spectrometry- and nuclear magnetic resonance-based metabolomic studies comparing diseased versus healthy individuals have shown that microbial metabolites are often the compounds most markedly altered in the disease state. Recent studies suggest that several of these metabolites that derive from microbial transformation of dietary components have significant effects on physiological processes such as gut and immune homeostasis, energy metabolism, vascular function, and neurological behavior. Here, we review several of the most intriguing diet-dependent metabolites that may impact host physiology and may therefore be appropriate targets for therapeutic interventions, such as short-chain fatty acids, trimethylamine N-oxide, tryptophan and tyrosine derivatives, and oxidized fatty acids. Read More