Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation
Open accessAbstract
Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs. In addition, both Olfr78 and G protein-coupled receptor 41 (Gpr41), another SCFA receptor, are expressed in smooth muscle cells of small resistance vessels. Propionate, a SCFA shown to induce vasodilation ex vivo, produces an acute hypotensive response in wild-type mice. This effect is differentially modulated by disruption of Olfr78 and Gpr41 expression. SCFAs are end products of fermentation by the gut microbiota and are absorbed into the circulation. Antibiotic treatment reduces the biomass of the gut microbiota and elevates blood pressure in Olfr78 knockout mice. We conclude that SCFAs produced by the gut microbiota modulate blood pressure via Olfr78 and Gpr41.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
OR51E2 is activated by acetate and propionate and has been detected in the brain of rodents, but not humans.
“The only one activated by acetate and propionate is the GPCR olfactory receptor family 51 subfamily member 2 (OR51E2 for humans, olfactory receptor 78 -Olfr78 for mice) (Pluznick et al., 2013), which has been detected in the brain of rodents, but not humans (Yuan et al., 2001).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Pluznick et al., 2013
Olfr78 and Gpr41 participate in host blood pressure regulation.
“Early mechanistic studies by Pluznick and colleagues substantiated this idea by demonstrating the G-protein coupled SCFA receptors olfactory receptor 78 (Olfr78) and G-protein receptor 41 (Gpr41) participate in host blood pressure regulation59–61.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [60]
Pluznick et al. demonstrated that microbiota produce SCFA to modulate blood pressure through SCFA interaction with host GPCRs Olfr78 and Gpr41, and antibiotic treatment can alter blood pressure in Olfr78 knockout mice.
“Pluznick et al. demonstrated that microbiota could produce SCFA to modulate blood pressure through short-chain fatty acid interaction with the host G protein-coupled receptors (GPCRs) Olfr78 and Gpr41; antibiotic treatment can then alter blood pressure in Olfr78 knockout mice83.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [83]
Interventions that target the gut microbiota, such as a high-fibre diet, probiotics and antibiotics, have blood-pressure lowering effects in animal models and in patients with hypertension.
“Finally, studies in animal models and in patients with hypertension have reported that interventions that target the gut microbiota, such as a high-fibre diet, probiotics and antibiotics, have blood-pressure lowering effects87,92–99.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [93]
Administration of propionate modulates blood pressure in mice, likely via binding to G protein-coupled receptor 41 and olfactory receptor 78.
“Administration of propionate has also been reported to modulate blood pressure in mice, likely via binding to the G protein-coupled receptor 41 (GPR41) and olfactory receptor 78 (OLFR78; also known as OR51E2)93,94.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [93]
Cites
UniFrac: a New Phylogenetic Method for Comparing Microbial Communities
Lozupone, C., & Knight, R. (2005) · Applied and Environmental Microbiology · doi:10.1128/aem.71.12.8228-8235.2005 · Cited by 8,227 · see citing works
Enterotypes of the human gut microbiome
MetaHIT Consortium (additional members), Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D. R., Fernandes, G. R., Tap, J., Bruls, T., et al. (2011) · Nature · doi:10.1038/nature09944 · Cited by 7,548 · see citing works
A novel multigene family may encode odorant receptors: A molecular basis for odor recognition
Buck, L., & Axel, R. (1991) · Cell · doi:10.1016/0092-8674(91)90418-x · Cited by 4,987 · see citing works
Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis
Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., & Medzhitov, R. (2004) · Cell · doi:10.1016/j.cell.2004.07.002 · Cited by 4,251 · see citing works
Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43
Maslowski, K. M., Vieira, A. T., Ng, A., Kranich, J., Sierro, F., Yu, D., Schilter, H. C., Rolph, M. S., Mackay, F., Artis, D., et al. (2009) · Nature · doi:10.1038/nature08530 · Cited by 3,241 · see citing works
Short chain fatty acids in human large intestine, portal, hepatic and venous blood
Cummings, J. H., Pomare, E. W., Branch, W. J., Naylor, C. P., & Macfarlane, G. T. (1987) · Gut · doi:10.1136/gut.28.10.1221 · Cited by 3,119 · see citing works
Human nutrition, the gut microbiome and the immune system
Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L., & Gordon, J. I. (2011) · Nature · doi:10.1038/nature10213 · Cited by 2,588 · see citing works
Self-citationBrown, A. J., Goldsworthy, S. M., Barnes, A. A., Eilert, M. M., Tcheang, L., Daniels, D., Muir, A. I., Wigglesworth, M. J., Kinghorn, I., Fraser, N. J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211609200 · Cited by 2,409 · see citing works
Innate immunity and intestinal microbiota in the development of Type 1 diabetes
Wen, L., Ley, R. E., Volchkov, P. Y., Stranges, P. B., Avanesyan, L., Stonebraker, A. C., Hu, C., Wong, F. S., Szot, G. L., Bluestone, J. A., et al. (2008) · Nature · doi:10.1038/nature07336 · Cited by 1,921 · see citing works
Self-citationLe Poul, E., Loison, C., Struyf, S., Springael, J.-Y., Lannoy, V., Decobecq, M.-E., Brezillon, S., Dupriez, V., Vassart, G., Van Damme, J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301403200 · Cited by 1,651 · see citing works
Samuel, B. S., Shaito, A., Motoike, T., Rey, F. E., Backhed, F., Manchester, J. K., Hammer, R. E., Williams, S. C., Crowley, J., Yanagisawa, M., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808567105 · Cited by 1,564 · see citing works
Self-citationKimura, I., Inoue, D., Maeda, T., Hara, T., Ichimura, A., Miyauchi, S., Kobayashi, M., Hirasawa, A., & Tsujimoto, G. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016088108 · Cited by 1,106 · see citing works
Human metabolic phenotype diversity and its association with diet and blood pressure
Holmes, E., Loo, R. L., Stamler, J., Bictash, M., Yap, I. K. S., Chan, Q., Ebbels, T., De Iorio, M., Brown, I. J., Veselkov, K. A., et al. (2008) · Nature · doi:10.1038/nature06882 · Cited by 1,054 · see citing works
Peripheral education of the immune system by colonic commensal microbiota
Lathrop, S. K., Bloom, S. M., Rao, S. M., Nutsch, K., Lio, C.-W., Santacruz, N., Peterson, D. A., Stappenbeck, T. S., & Hsieh, C.-S. (2011) · Nature · doi:10.1038/nature10434 · Cited by 1,034 · see citing works
Circulation: Overall Regulation
Guyton, A. C., Coleman, T. G., & Granger, H. J. (1972) · Annual Review of Physiology · doi:10.1146/annurev.ph.34.030172.000305 · Cited by 870 · see citing works
Identification of a Testicular Odorant Receptor Mediating Human Sperm Chemotaxis
Spehr, M., Gisselmann, G., Poplawski, A., Riffell, J. A., Wetzel, C. H., Zimmer, R. K., & Hatt, H. H. (2003) · Science · doi:10.1126/science.1080376 · Cited by 769 · see citing works
Absorption of Short-Chain Fatty Acids by the Colon
Ruppin, H., Bar-Meir, S., Soergel, K. H., Wood, C. M., & Schmitt, M. G. (1980) · Gastroenterology · doi:10.1016/s0016-5085(19)30508-6 · Cited by 736 · see citing works
Morphology, physiology, and molecular biology of renin secretion
Hackenthal, E., Paul, M., Ganten, D., & Taugner, R. (1990) · Physiological Reviews · doi:10.1152/physrev.1990.70.4.1067 · Cited by 614 · see citing works
RTP Family Members Induce Functional Expression of Mammalian Odorant Receptors
Saito, H., Kubota, M., Roberts, R. W., Chi, Q., & Matsunami, H. (2004) · Cell · doi:10.1016/j.cell.2004.11.021 · Cited by 608 · see citing works
Odor Coding by a Mammalian Receptor Repertoire
Saito, H., Chi, Q., Zhuang, H., Matsunami, H., & Mainland, J. D. (2009) · Science Signaling · doi:10.1126/scisignal.2000016 · Cited by 563 · see citing works
Wong, S. T., Trinh, K., Hacker, B., Chan, G. C. K., Lowe, G., Gaggar, A., Xia, Z., Gold, G. H., & Storm, D. R. (2000) · Neuron · doi:10.1016/s0896-6273(00)00060-x · Cited by 470 · see citing works
Whelton, S. P., Hyre, A. D., Pedersen, B., Yi, Y., Whelton, P. K., & He, J. (2005) · Journal of Hypertension · doi:10.1097/01.hjh.0000160199.51158.cf · Cited by 465 · see citing works
Odorant Receptor Expression Defines Functional Units in the Mouse Olfactory System
Bozza, T. C., Feinstein, P. G., Zheng, C., & Mombaerts, P. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-08-03033.2002 · Cited by 408 · see citing works
Occurrence, absorption and metabolism of short chain fatty acids in the digestive tract of mammals
Bugaut, M. (1987) · Comparative Biochemistry and Physiology Part B Comparative Biochemistry · doi:10.1016/0305-0491(87)90433-0 · Cited by 366 · see citing works
Activation of an Olfactory Receptor Inhibits Proliferation of Prostate Cancer Cells
Neuhaus, E. M., Zhang, W., Gelis, L., Deng, Y., Noldus, J., & Hatt, H. H. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.012096 · Cited by 260 · see citing works
Functional expression of the olfactory signaling system in the kidney
Pluznick, J. L., Zou, D., Zhang, X., Yan, Q., Rodriguez‐Gil, D. J., Eisner, C. B., Wells, E., Greer, C. A., Wang, T., Firestein, S., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812859106 · Cited by 225 · see citing works
Self-citationMOR23 Promotes Muscle Regeneration and Regulates Cell Adhesion and Migration
Griffin, C. A., Kafadar, K. A., & Pavlath, G. K. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.09.004 · Cited by 214 · see citing works
Bozza, T. C., Vassalli, A., Fuss, S. H., Zhang, J.-J., Weiland, B., Pacifico, R., Feinstein, P. G., & Mombaerts, P. (2009) · Neuron · doi:10.1016/j.neuron.2008.11.010 · Cited by 198 · see citing works
Short chain fatty acids dilate isolated human colonic resistance arteries.
Mortensen, F. V., Nielsen, H. K., Mulvany, M. J., & Hessov, I. (1990) · Gut · doi:10.1136/gut.31.12.1391 · Cited by 197 · see citing works
Zhuang, H., & Matsunami, H. (2008) · Nature Protocols · doi:10.1038/nprot.2008.120 · Cited by 196 · see citing works
The Collecting Duct Is the Major Source of Prorenin in Diabetes
Kang, J. J., Toma, I., Sipos, A., et al. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.107268 · Cited by 174 · see citing works
Self-citationLu, M. M., Echeverri, F., & Moyer, B. D. (2003) · Traffic · doi:10.1034/j.1600-0854.2003.00097.x · Cited by 167 · see citing works
Activation of the Succinate Receptor GPR91 in Macula Densa Cells Causes Renin Release
Vargas, S. L., Toma, I., Kang, J. J., Meer, E. J., & Peti‐Peterdi, J. (2009) · Journal of the American Society of Nephrology · doi:10.1681/asn.2008070740 · Cited by 153 · see citing works
Self-citationLoss of Oriented Cell Division Does not Initiate Cyst Formation
Nishio, S., Tian, X., Gallagher, A., Yu, Z., Patel, V., Igarashi, P., & Somlo, S. (2009) · Journal of the American Society of Nephrology · doi:10.1681/asn.2009060603 · Cited by 137 · see citing works
Functional mosaic organization of mouse olfactory receptor neurons
Ma, M., & Shepherd, G. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220301797 · Cited by 127 · see citing works
Peters, S. G., Pomare, E. W., & Fisher, C. A. (1992) · Gut · doi:10.1136/gut.33.9.1249 · Cited by 124 · see citing works
Ric-8B promotes functional expression of odorant receptors
Dannecker, L. E. C. V., Mercadante, A. F., & Malnic, B. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600697103 · Cited by 116 · see citing works
Vasorelaxant effects of short chain fatty acid salts in rat caudal artery
Nutting, C. W., Islam, S., & Daugirdas, J. T. (1991) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1991.261.2.h561 · Cited by 99 · see citing works
Chen, L., Kim, S. M., Oppermann, M., Faulhaber‐Walter, R., Huang, Y. G., Mizel, D. E., Chen, M., Sequeira-Lόpez, M. L. S., Weinstein, L. S., Gómez, R. A., et al. (2006) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00193.2006 · Cited by 97 · see citing works
Acetate and bicarbonate fluctuations and acetate intolerance during dialysis
Pagel, M. D., Ahmad, S., Vizzo, J. E., et al. (1982) · Kidney International · doi:10.1038/ki.1982.54 · Cited by 90 · see citing works
Sustained Hypertension in the Rat Induced by Chronic Blockade of Nitric Oxide Production
Johnson, R. A., & Freeman, R. K. (1992) · American Journal of Hypertension · doi:10.1093/ajh/5.12.919 · Cited by 88 · see citing works
Cells in the vomeronasal organ express odorant receptors but project to the accessory olfactory bulb
Lévai, O., Feistel, T., Breer, H., & Strotmann, J. M. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.21067 · Cited by 80 · see citing works
Decreased Intracellular Calcium Stimulates Renin Release via Calcium-Inhibitable Adenylyl Cyclase
Ortiz‐Capisano, M. C., Ortiz, P. A., Harding, P., Garvin, J. L., & Beierwaltes, W. H. (2006) · Hypertension · doi:10.1161/01.hyp.0000250708.04205.d4 · Cited by 79 · see citing works
Real-time imaging of renin release in vitro
Peti‐Peterdi, J., Fintha, A., Fuson, A. L., Tousson, A., & Chow, R. H.-P. (2004) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00420.2003 · Cited by 78 · see citing works
Self-citationOlfactory receptor expressed in ganglia of the autonomic nervous system
Weber, M., Pehl, U., Breer, H., & Strotmann, J. M. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10164 · Cited by 54 · see citing works
The Role of Acetate in the Etiology of Symptomatic Hypotension
Keshaviah, P. (1982) · Artificial Organs · doi:10.1111/j.1525-1594.1982.tb04130.x · Cited by 50 · see citing works
Immunocytochemical localization of Na+ channels in rat kidney medulla
Brown, D. J., Sorscher, E. J., Ausiello, D. A., et al. (1989) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1989.256.2.f366 · Cited by 43 · see citing works
Tokarev, D., & Ježová, D. (2000) · PubMed · Cited by 9 · see citing works
Detecting the Surface Localization and Cytoplasmic Cleavage of Membrane-Bound Proteins
Chapin, H. C., Rajendran, V., Capasso, A., et al. (2009) · Methods in cell biology · doi:10.1016/s0091-679x(08)94011-5 · Cited by 6 · see citing works
Cholinergic signal transduction in the mouse sphenopalatine ganglion
Rafalzik, S., Pehl, U., Ott, D., et al. (2008) · Brain Research · doi:10.1016/j.brainres.2008.08.095 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
The role of short-chain fatty acids in microbiota–gut–brain communication
Dalile, B., Van Oudenhove, L., Vervliet, B., & Verbeke, K. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0157-3 · Cited by 3,357 · see citing works
Gut microbiota, metabolites and host immunity
Rooks, M. G., & Garrett, W. S. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.42 · Cited by 3,409 · see citing works
Short-chain fatty acids in control of body weight and insulin sensitivity
Canfora, E. E., Jocken, J. W., & Blaak, E. E. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.128 · Cited by 2,298 · see citing works
Gut Dysbiosis Is Linked to Hypertension
Yang, T., Santisteban, M. M., Rodriguez, V., Li, E., Ahmari, N., Carvajal, J. M., Zadeh, M., Gong, M., Qi, Y., Zubcevic, J., et al. (2015) · Hypertension · doi:10.1161/hypertensionaha.115.05315 · Cited by 1,478 · see citing works
Marques, F. Z., Nelson, E., Chu, P.-Y., Horlock, D., Fiedler, A., Ziemann, M., Tan, J. K., Kuruppu, S., Rajapakse, N. W., El-Osta, A., et al. (2017) · Circulation · doi:10.1161/circulationaha.116.024545 · Cited by 1,065 · see citing works
Gut microbiota and cardiovascular disease.
Witkowski, M., Weeks, T. L., & Hazen, S. L. (2020) · Circulation Research · doi:10.1161/circresaha.120.316242 · Cited by 1,051 · see citing works
Scheiman, J., Luber, J. M., Chavkin, T. A., MacDonald, T., Tung, A., Pham, L.-D., Wibowo, M. C., Wurth, R. C., Punthambaker, S., Tierney, B. T., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0485-4 · Cited by 892 · see citing works
Nogal, A., Valdes, A. M., & Menni, C. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1897212 · Cited by 917 · see citing works
Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation
Kasubuchi, M., Hasegawa, S., Hiramatsu, T., Ichimura, A., & Kimura, I. (2015) · Nutrients · doi:10.3390/nu7042839 · Cited by 904 · see citing works
Postler, T. S., & Ghosh, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.008 · Cited by 876 · see citing works
“A fourth SCFA-responsive GPCR, the olfactory receptor 51E2 (OR51E2, also known as Olfr78 in mice), is expressed by some cells of the intestinal epithelium but has not been connected to the immune system (Fleischer et al., 2015; Pluznick et al., 2013).”
BackgroundThe neuropharmacology of butyrate: the bread and butter of the microbiota-gut-brain axis
Stilling, R. M., van de Wouw, M., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2016) · Neurochemistry International · doi:10.1016/j.neuint.2016.06.011 · Cited by 891 · see citing works
Dietary metabolism, the gut microbiome, and heart failure
Tang, W. H. W., Li, D. Y., & Hazen, S. L. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0108-7 · Cited by 789 · see citing works
The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease
Yang, T., Richards, E. M., Pepine, C. J., & Raizada, M. K. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0018-2 · Cited by 753 · see citing works
Gut microbiota-derived short-chain Fatty acids, T cells, and inflammation
Kim, C. H., Park, J., & Kim, M. (2014) · Immune Network · doi:10.4110/in.2014.14.6.277 · Cited by 704 · see citing works
Role of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health
Chambers, E. S., Preston, T., Frost, G., & Morrison, D. J. (2018) · Current Nutrition Reports · doi:10.1007/s13668-018-0248-8 · Cited by 691 · see citing works
The role of the microbiome in NAFLD and NASH
Kolodziejczyk, A. A., Zheng, D., Shibolet, O., & Elinav, E. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201809302 · Cited by 523 · see citing works
Hypertension-Linked Pathophysiological Alterations in the Gut
Santisteban, M. M., Qi, Y., Zubcevic, J., Kim, S., Yang, T., Shenoy, V., Cole-Jeffrey, C. T., Lobaton, G. O., Stewart, D. C., Rubiano, A., et al. (2017) · Circulation Research · doi:10.1161/circresaha.116.309006 · Cited by 525 · see citing works
Microbiota-gut-brain axis: Modulator of host metabolism and appetite
van de Wouw, M., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2017) · The Journal of Nutrition · doi:10.3945/jn.116.240481 · Cited by 461 · see citing works
The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease
Vogt, N. M., Romano, K. A., Darst, B. F., Engelman, C. D., Johnson, S. C., Carlsson, C. M., Asthana, S., Blennow, K., Zetterberg, H., Bendlin, B. B., et al. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-018-0451-2 · Cited by 471 · see citing works
Self-citationZeng, H., Umar, S., Rust, B., Lazarova, D., & Bordonaro, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20051214 · Cited by 480 · see citing works
Microbial modulation of cardiovascular disease
Brown, J. M., & Hazen, S. L. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.149 · Cited by 440 · see citing works
Natarajan, N., Hori, D., Flavahan, S., Steppan, J., Flavahan, N. A., Berkowitz, D. E., & Pluznick, J. L. (2016) · Physiological Genomics · doi:10.1152/physiolgenomics.00089.2016 · Cited by 441 · see citing works
Self-citationEvidence for a link between gut microbiota and hypertension in the Dahl rat
Mell, B., Jala, V. R., Mathew, A. V., Byun, J., Waghulde, H., Zhang, Y., Haribabu, B., Vijay-Kumar, M., Pennathur, S., & Joe, B. (2015) · Physiological Genomics · doi:10.1152/physiolgenomics.00136.2014 · Cited by 400 · see citing works
Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids
Kim, C. H. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-00625-0 · Cited by 404 · see citing works
Role of the Gut Microbiome in Uremia: A Potential Therapeutic Target
Ramezani, A., Massy, Z. A., Meijers, B., Evenepoel, P., Vanholder, R., & Raj, D. S. (2016) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2015.09.027 · Cited by 394 · see citing works
Probiotics, prebiotics and amelioration of diseases
Tsai, Y.-L., Lin, T.-L., Chang, C.-J., Wu, T.-R., Lai, W.-F., Lu, C.-C., & Lai, H.-C. (2019) · Journal of Biomedical Science · doi:10.1186/s12929-018-0493-6 · Cited by 388 · see citing works
Immune regulation by microbiome metabolites
Kim, C. H. (2018) · Immunology · doi:10.1111/imm.12930 · Cited by 375 · see citing works
RETRACTED ARTICLE: Role of the gut microbiome in chronic diseases: a narrative review
Vijay, A., & Valdes, A. M. (2022) · European Journal of Clinical Nutrition · doi:10.1038/s41430-021-00991-6 · Cited by 361 · see citing works
RetractedGut Microbiota Promote Angiotensin II–Induced Arterial Hypertension and Vascular Dysfunction
Karbach, S. H., Schönfelder, T., Brandão, I., Wilms, E., Hörmann, N., Jäckel, S., Schüler, R., Finger, S., Knorr, M., Lagrange, J., et al. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003698 · Cited by 378 · see citing works
A novel SCFA receptor, the microbiota, and blood pressure regulation
Pluznick, J. (2014) · Gut Microbes · doi:10.4161/gmic.27492 · Cited by 374 · see citing works
Self-citationConnecting the immune system, systemic chronic inflammation and the gut microbiome: the role of sex
Rizzetto, L., Fava, F., Tuohy, K. M., & Selmi, C. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.05.008 · Cited by 331 · see citing works
Role of the Gut Microbiome in Obstructive Sleep Apnea–Induced Hypertension
Durgan, D. J., Ganesh, B. P., Cope, J. L., Ajami, N. J., Phillips, S. C., Petrosino, J. F., Hollister, E. B., & Bryan, R. M. (2016) · Hypertension · doi:10.1161/hypertensionaha.115.06672 · Cited by 327 · see citing works
Uribe-Herranz, M., Rafail, S., Beghi, S., Gil-de-Gómez, L., Verginadis, I., Bittinger, K., Pustylnikov, S., Pierini, S., Perales-Linares, R., Blair, I. A., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci124332 · Cited by 316 · see citing works
Microbial Short-Chain Fatty Acids and Blood Pressure Regulation
Pluznick, J. L. (2017) · Current Hypertension Reports · doi:10.1007/s11906-017-0722-5 · Cited by 301 · see citing works
Self-citationGut microbiome and kidney disease: a bidirectional relationship
Al Khodor, S., & Shatat, I. F. (2017) · Pediatric Nephrology · doi:10.1007/s00467-016-3392-7 · Cited by 191 · see citing works
Skye, S. M., Zhu, W., Romano, K. A., Guo, C.-J., Wang, Z., Jia, X., Kirsop, J., Haag, B., Lang, J. M., DiDonato, J. A., et al. (2018) · Circulation Research · doi:10.1161/circresaha.118.313142 · Cited by 189 · see citing works
Self-citationRegulation of the Renal NaCl Cotransporter and Its Role in Potassium Homeostasis
Hoorn, E. J., Gritter, M., Cuevas, C. A., & Fenton, R. A. (2020) · Physiological Reviews · doi:10.1152/physrev.00044.2018 · Cited by 163 · see citing works
Park, J., Goergen, C. J., HogenEsch, H., & Kim, C. H. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502046 · Cited by 166 · see citing works
Gut microbiota–derived short-chain fatty acids and kidney diseases
Li, L., Ma, L., & Fu, P. (2017) · Drug Design, Development and Therapy · doi:10.2147/dddt.s150825 · Cited by 164 · see citing works
Soy and Gut Microbiota: Interaction and Implication for Human Health
Huang, H., Krishnan, H. B., Pham, Q., Yu, L. L., & Wang, T. T. Y. (2016) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.6b03725 · Cited by 138 · see citing works
Self-citationLagoumintzis, G., & Patrinos, G. P. (2023) · Human Genomics · doi:10.1186/s40246-023-00561-w · Cited by 132 · see citing works
Masse, K. E., & Lu, V. B. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1169624 · Cited by 120 · see citing works
“Originally discovered in olfactory epithelium, the olfactory receptor subfamily 51E1/2 (OR51E1/2; Olfr558/Olfr78 in mouse) are other receptors responsive to SCFAs (82).”
BackgroundFoley, K. A., MacFabe, D. F., Vaz, A., Ossenkopp, K., & Kavaliers, M. (2014) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2014.04.001 · Cited by 116 · see citing works
KUWAHARA, A., MATSUDA, K., KUWAHARA, Y., ASANO, S., INUI, T., & MARUNAKA, Y. (2020) · Biomedical Research · doi:10.2220/biomedres.41.199 · Cited by 112 · see citing works
Pontes, K. S. D. S., Guedes, M. R., Cunha, M. R. D., Mattos, S. D. S., Barreto Silva, M. I., Neves, M. F., Marques, B. C. A. A., & Klein, M. R. S. T. (2021) · Clinical Nutrition · doi:10.1016/j.clnu.2021.06.023 · Cited by 86 · see citing works
The microbiota and chronic kidney diseases: a double‐edged sword
Felizardo, R. J. F., Castoldi, A., Andrade‐Oliveira, V., & Câmara, N. O. S. (2016) · Clinical & Translational Immunology · doi:10.1038/cti.2016.36 · Cited by 85 · see citing works
Gut-microbiota derived bioactive metabolites and their functions in host physiology
Debnath, N., Kumar, R., Kumar, A., Mehta, P. K., & Yadav, A. K. (2021) · Biotechnology and Genetic Engineering Reviews · doi:10.1080/02648725.2021.1989847 · Cited by 77 · see citing works
Gut–Brain Axis in Regulation of Blood Pressure
Yang, T., & Zubcevic, J. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00845 · Cited by 74 · see citing works
Polsinelli, V. B., Sinha, A., & Shah, S. J. (2017) · Current Heart Failure Reports · doi:10.1007/s11897-017-0370-8 · Cited by 64 · see citing works
Gut hormones and gut microbiota: implications for kidney function and hypertension
Afsar, B., Vaziri, N. D., Aslan, G., Tarim, K., & Kanbay, M. (2016) · Journal of the American Society of Hypertension · doi:10.1016/j.jash.2016.10.007 · Cited by 63 · see citing works
Wang, X., Shang, Y., Wei, Q., Wu, X., Dou, H., Zhang, H., Zhou, S., Sha, W., Sun, G., Ma, S., et al. (2022) · Microbial Ecology · doi:10.1007/s00248-021-01806-8 · Cited by 36 · see citing works
- Authors
- Pluznick, J. L., Protzko, R. J., Gevorgyan, H., Peterlin, Z., Sipos, A., Han, J., Brunet, I., Wan, L.-X., Rey, F., Wang, T., Firestein, S. J., Yanagisawa, M., Gordon, J. I., Eichmann, A., Peti-Peterdi, J., & Caplan, M. J.
- Affiliations
- Johns Hopkins University (US)
- University of Southern California (US)
- Columbia University (US)
- Yale University (US)
- Collège de France (FR)
- Washington University in St. Louis (US)
- Howard Hughes Medical Institute (US)
- Departments of Physiology and Biophysics and Medicine, University of Southern California, Los Angeles, CA 90033;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-02-11
- Volume
- 110
- Issue
- 11
- Pages
- 4410-4415
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3600440
- OpenAlex
- W1994863439
- Cited by
- 1,191
- References
- 50
- Citations by year
- 2026: 91 · 2025: 93 · 2024: 104 · 2023: 108 · 2022: 130 · 2021: 145 · 2020: 108 · 2019: 96 · 2018: 87 · 2017: 68 · 2016: 52 · 2015: 51 · 2014: 33 · 2013: 21
- FWCI
- 35.55
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK030292, DK 17433, DK 64324, DK-081610, P01DK017433, K99DK081610, R00DK081610, P30DK079310, R01DK064324)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- GPR41, short-chain fatty acids, gut microbiota, renin secretion, blood pressure regulation, juxtaglomerular apparatus, propionate, vasodilation, G protein-coupled receptors, gut-kidney axis
- MeSH terms
- Animals, Blood Pressure, Gene Expression Regulation, Hypertension, Intestinal Mucosa, Intestines, Kidney, Propionates, Renin, Vasodilation, Signal Transduction, Receptors, Odorant, Mice, Knockout, Biomass, Receptors, G-Protein-Coupled, Mice, Metagenome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
