Olfaction in the kidney: 'smelling' gut microbial metabolites.

2016Apr
Exp. Physiol.
Exp Physiol 2016 Apr 27;101(4):478-81. Epub 2015 Aug 27.
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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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Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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2016Apr
Exp. Physiol.
Exp Physiol 2016 Apr 27;101(4):478-81. Epub 2015 Aug 27.

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.

2014Jun
Gut Microbes
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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. In addition, propionate modifies renin release in an Olfr78-dependent manner. Our study also demonstrated that antibiotic treatment modulates blood pressure in Olfr78 null mice, indicating that SCFAs produced by the gut microbiota likely influence blood pressure regulation. In this addendum, we summarize the findings of our recent study and provide a perspective on the implications of the interactions between the gut microbiota and blood pressure control.

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. In this review, we summarize the roles of gut microbial SCFAs in the host energy regulation and present an overview of the current understanding of its physiological functions.

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). SCFAs can directly activate G-coupled-receptors, inhibit histone deacetylases, and serve as energy substrates. They thus affect various physiological processes and may contribute to health and disease.

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. Such interventions will require modulating either bacterial species or the bacterial biosynthetic enzymes required to produce these metabolites, so we briefly describe the current understanding of the bacterial and enzymatic pathways involved in their biosynthesis and summarize their molecular mechanisms of action. We then discuss in more detail the impact of these metabolites on health and disease, and review current strategies to modulate levels of these metabolites to promote human health. We also suggest future studies that are needed to realize the full therapeutic potential of targeting the gut microbiota.

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Affiliation Details

  • Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Johns Hopkins University School of Medicine
Affiliation Johns Hopkins University School of Medicine, Baltimore, MD, USA.