Succinate metabolism and its regulation of host-microbe interactions

References

• Canfora EE, Meex RCR, Venema K, Blaak EE. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol. 2019;15:261–20. doi:10.1038/s41574-019-0156-z.
   PubMed Web of Science ®Google Scholar
• Glassner KL, Abraham BP, Quigley EMM. The microbiome and inflammatory bowel disease. J Allergy Clin Immunol. 2020;145:16–27. doi:10.1016/j.jaci.2019.11.003.
   PubMed Web of Science ®Google Scholar
• Van de Wiele T, Van Praet JT, Marzorati M, Drennan MB, Elewaut D. How the microbiota shapes rheumatic diseases. Nat Rev Rheumatol. 2016;12:398–411. doi:10.1038/nrrheum.2016.85.
   PubMed Web of Science ®Google Scholar
• Yuan Y, Xu Y, Xu J, Liang B, Cai X, Zhu C, Wang L, Wang S, Zhu X, Gao P, et al. Succinate promotes skeletal muscle protein synthesis via Erk1/2 signaling pathway. Mol Med Rep. 2017;16:7361–7366. doi:10.3892/mmr.2017.7554.
   PubMed Web of Science ®Google Scholar
• Wang T, Xu YQ, Yuan YX, Xu PW, Zhang C, Li F, Wang L-N, Yin C, Zhang L, Cai X-C, et al. Succinate induces skeletal muscle fiber remodeling via SUNCR1 signaling. EMBO Rep. 2019;20:e47892. doi:10.15252/embr.201947892.
   PubMed Web of Science ®Google Scholar
• Reddy A, Bozi LHM, Yaghi OK, Mills EL, Xiao H, Nicholson HE, Paschini M, Paulo JA, Garrity R, Laznik-Bogoslavski D, et al. PH-Gated succinate secretion regulates muscle remodeling in response to exercise. Cell. 2020;183:62–75 e17. doi:10.1016/j.cell.2020.08.039.
   PubMed Web of Science ®Google Scholar
• Wang K, Liao M, Zhou N, Bao L, Ma K, Zheng Z, Wang Y, Liu C, Wang W, Wang J, et al. Parabacteroides distasonis alleviates obesity and metabolic dysfunctions via production of succinate and secondary bile acids. Cell Rep. 2019;26:222–35 e5. doi:10.1016/j.celrep.2018.12.028.
   PubMed Web of Science ®Google Scholar
• Ives SJ, Zaleski KS, Slocum C, Escudero D, Sheridan C, Legesse S, Vidal K, Lagalwar S, Reynolds TH. The effect of succinic acid on the metabolic profile in high-fat diet-induced obesity and insulin resistance. Physiol Rep. 2020;8:e14630. doi:10.14814/phy2.14630.
   PubMed Web of Science ®Google Scholar
• Macias-Ceja DC, Ortiz-Masia D, Salvador P, Gisbert-Ferrandiz L, Hernandez C, Hausmann M, Rogler G, Esplugues JV, Hinojosa J, Alós R, et al. Succinate receptor mediates intestinal inflammation and fibrosis. Mucosal Immunol. 2019;12:178–187. doi:10.1038/s41385-018-0087-3.
   PubMed Web of Science ®Google Scholar
• Ooi M, Nishiumi S, Yoshie T, Shiomi Y, Kohashi M, Fukunaga K, Nakamura S, Matsumoto T, Hatano N, Shinohara M, et al. GC/MS-based profiling of amino acids and TCA cycle-related molecules in ulcerative colitis. Inflamm Res. 2011;60:831–840. doi:10.1007/s00011-011-0340-7.
   PubMed Web of Science ®Google Scholar
• Zhang J, Wang YT, Miller JH, Day MM, Munger JC, Brookes PS. Accumulation of succinate in cardiac ischemia primarily occurs via canonical krebs cycle activity. Cell Rep. 2018;23:2617–2628. doi:10.1016/j.celrep.2018.04.104.
   PubMed Web of Science ®Google Scholar
• Bardella C, Pollard PJ, Tomlinson I. SDH mutations in cancer. Biochimica et Biophysica Acta (BBA) - Bioenergetics. 2011;1807:1432–1443. doi:10.1016/j.bbabio.2011.07.003.
   PubMed Web of Science ®Google Scholar
• Ricketts C, Woodward ER, Killick P, Morris MR, Astuti D, Latif F, Maher ER. Germline SDHB mutations and familial renal cell carcinoma. J Natl Cancer Inst. 2008;100:1260–1262. doi:10.1093/jnci/djn254.
   PubMedGoogle Scholar
• Huang LY, Ma JY, Song JX, Xu JJ, Hong R, Fan HD, Cai H, Wang W, Wang Y-L, Hu Z-L, et al. Ischemic accumulation of succinate induces Cdc42 succinylation and inhibits neural stem cell proliferation after cerebral ischemia/reperfusion. Neural Regen Res. 2023;18:1040–1045. doi:10.4103/1673-5374.355821.
   PubMed Web of Science ®Google Scholar
• Song H, Lee SY. Production of succinic acid by bacterial fermentation. Enzyme Microb Technol. 2006;39:352–361. doi:10.1016/j.enzmictec.2005.11.043.
   Web of Science ®Google Scholar
• Ahn JH, Seo H, Park W, Seok J, Lee JA, Kim WJ, Kim GB, Kim K-J, Lee SY. Enhanced succinic acid production by Mannheimia employing optimal malate dehydrogenase. Nat Commun. 2020;11:1970. doi:10.1038/s41467-020-15839-z.
   PubMed Web of Science ®Google Scholar
• Li C, Ong KL, Cui Z, Sang Z, Li X, Patria RD, Qi Q, Fickers P, Yan J, Lin CSK. Promising advancement in fermentative succinic acid production by yeast hosts. J Hazard Mater. 2021;401:123414. doi:10.1016/j.jhazmat.2020.123414.
   PubMed Web of Science ®Google Scholar
• Litsanov B, Brocker M, Bott M. Glycerol as a substrate for aerobic succinate production in minimal medium with Corynebacterium glutamicum. Microb Biotechnol. 2013;6:189–195. doi:10.1111/j.1751-7915.2012.00347.x.
   PubMed Web of Science ®Google Scholar
• Fernandez-Veledo S, Vendrell J. Gut microbiota-derived succinate: friend or foe in human metabolic diseases? Rev Endocr Metab Disord. 2019;20:439–447. doi:10.1007/s11154-019-09513-z.
   PubMed Web of Science ®Google Scholar
• Reichardt N, Duncan SH, Young P, Belenguer A, McWilliam Leitch C, Scott KP, Flint HJ, Louis P. Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. Isme J. 2014;8:1323–1335. doi:10.1038/ismej.2014.14.
   PubMed Web of Science ®Google Scholar
• Krautkramer KA, Fan J, Backhed F. Gut microbial metabolites as multi-kingdom intermediates. Nat Rev Microbiol. 2021;19:77–94. doi:10.1038/s41579-020-0438-4.
   PubMed Web of Science ®Google Scholar
• Louis P, Flint HJ. Formation of propionate and butyrate by the human colonic microbiota. Environ Microbiol. 2017;19:29–41. doi:10.1111/1462-2920.13589.
   PubMed Web of Science ®Google Scholar
• Van der Werf MJ, Guettler MV, Jain MK, Zeikus JG. Environmental and physiological factors affecting the succinate product ratio during carbohydrate fermentation by Actinobacillus sp. 130Z. Arch Microbiol. 1997;167:332–342. doi:10.1007/s002030050452.
   PubMed Web of Science ®Google Scholar
• Strobel HJ. Vitamin B12-dependent propionate production by the ruminal bacterium Prevotella ruminicola 23. Appl Environ Microbiol. 1992;58:2331–2333. doi:10.1128/aem.58.7.2331-2333.1992.
   PubMed Web of Science ®Google Scholar
• Zhang B, Lingga C, Bowman C, Hackmann TJ, Pettinari MJ. A new pathway for forming acetate and synthesizing ATP during fermentation in bacteria. Appl Environ Microbiol. 2021;87:e0295920. doi:10.1128/AEM.02959-20.
   PubMed Web of Science ®Google Scholar
• Kwong WK, Zheng H, Moran NA. Convergent evolution of a modified, acetate-driven TCA cycle in bacteria. Nat Microbiol. 2017;2:17067. doi:10.1038/nmicrobiol.2017.67.
   PubMed Web of Science ®Google Scholar
• Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, Frezza C, Bernard NJ, Kelly B, Foley NH, et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature. 2013;496:238–242. doi:10.1038/nature11986.
   PubMed Web of Science ®Google Scholar
• Wong CG, Bottiglieri T, Snead OC 3rd. GABA, gamma-hydroxybutyric acid, and neurological disease. Ann Neurol. 2003;54(Suppl 6):S3–12. doi:10.1002/ana.10696.
   PubMedGoogle Scholar
• Watanabe Y, Nagai F, Morotomi M. Characterization of Phascolarctobacterium succinatutens sp. nov., an asaccharolytic, succinate-utilizing bacterium isolated from human feces. Appl Environ Microbiol. 2012;78:511–518. doi:10.1128/AEM.06035-11.
   PubMed Web of Science ®Google Scholar
• Ikeyama N, Murakami T, Toyoda A, Mori H, Iino T, Ohkuma M, Sakamoto M. Microbial interaction between the succinate-utilizing bacterium Phascolarctobacterium faecium and the gut commensal Bacteroides thetaiotaomicron. Microbiologyopen. 2020;9:e1111. doi:10.1002/mbo3.1111.
   PubMed Web of Science ®Google Scholar
• Kim YG, Sakamoto K, Seo SU, Pickard JM, Gillilland MG 3rd, Pudlo NA, Hoostal M, Li X, Wang TD, Feehley T, et al. Neonatal acquisition of Clostridia species protects against colonization by bacterial pathogens. Science. 2017;356:315–319. doi:10.1126/science.aag2029.
   PubMed Web of Science ®Google Scholar
• Ferreyra JA, Wu KJ, Hryckowian AJ, Bouley DM, Weimer BC, Sonnenburg JL. Gut microbiota-produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance. Cell Host Microbe. 2014;16:770–777. doi:10.1016/j.chom.2014.11.003.
   PubMed Web of Science ®Google Scholar
• Spiga L, Winter MG, Furtado de Carvalho T, Zhu W, Hughes ER, Gillis CC, Behrendt CL, Kim J, Chessa D, Andrews-Polymenis HL, et al. An oxidative central metabolism enables salmonella to utilize microbiota-derived succinate. Cell Host Microbe. 2017;22:291–301 e6. doi:10.1016/j.chom.2017.07.018.
   PubMed Web of Science ®Google Scholar
• Li X, Ren Y, Huang G, Zhang R, Zhang Y, Zhu W, Yu K. Succinate communicates pro-inflammatory signals to the host and regulates bile acid enterohepatic metabolism in a pig model. Food Funct. 2022;13:11070–11082. doi:10.1039/d2fo01958b.
   PubMed Web of Science ®Google Scholar
• Morotomi M, Nagai F, Sakon H, Tanaka R. Dialister succinatiphilus sp. nov. and Barnesiella intestinihominis sp. nov., isolated from human faeces. Int J Syst Evol Microbiol. 2008;58:2716–2720. doi:10.1099/ijs.0.2008/000810-0.
   PubMed Web of Science ®Google Scholar
• Makki K, Deehan EC, Walter J, Backhed F. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe. 2018;23:705–715. doi:10.1016/j.chom.2018.05.012.
   PubMed Web of Science ®Google Scholar
• Kovatcheva-Datchary P, Nilsson A, Akrami R, Lee YS, De Vadder F, Arora T, Hallen A, Martens E, Björck I, Bäckhed F. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of prevotella. Cell Metab. 2015;22:971–982. doi:10.1016/j.cmet.2015.10.001.
   PubMed Web of Science ®Google Scholar
• Ding N, Zhang X, Zhang XD, Jing J, Liu SS, Mu YP, Peng LL, Yan YJ, Xiao GM, Bi XY, et al. Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes. Gut. 2020;69:1608–1619. doi:10.1136/gutjnl-2019-319127.
   PubMed Web of Science ®Google Scholar
• Tan J, Ni D, Taitz J, Pinget GV, Read M, Senior A, Wali JA, Elnour R, Shanahan E, Wu H, et al. Dietary protein increases T-cell-independent sIga production through changes in gut microbiota-derived extracellular vesicles. Nat Commun. 2022;13:4336. doi:10.1038/s41467-022-31761-y.
   PubMed Web of Science ®Google Scholar
• De Vadder F, Kovatcheva-Datchary P, Zitoun C, Duchampt A, Backhed F, Mithieux G. Microbiota-Produced succinate improves glucose homeostasis via intestinal gluconeogenesis. Cell Metab. 2016;24:151–157. doi:10.1016/j.cmet.2016.06.013.
   PubMed Web of Science ®Google Scholar
• Jiang L, Shang M, Yu S, Liu Y, Zhang H, Zhou Y, Wang M, Wang T, Li H, Liu Z, et al. A high-fiber diet synergizes with Prevotella copri and exacerbates rheumatoid arthritis. Cell Mol Immunol. 2022. doi:10.1038/s41423-022-00934-6.
   Web of Science ®Google Scholar
• Fremder M, Kim SW, Khamaysi A, Shimshilashvili L, Eini-Rider H, Park IS, Hadad U, Cheon JH, Ohana E. A transepithelial pathway delivers succinate to macrophages, thus perpetuating their pro-inflammatory metabolic state. Cell Rep. 2021;36:109521. doi:10.1016/j.celrep.2021.109521.
   PubMed Web of Science ®Google Scholar
• Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, Reyes JA, Shah SA, LeLeiko N, Snapper SB, et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012;13:R79. doi:10.1186/gb-2012-13-9-r79.
   PubMed Web of Science ®Google Scholar
• Wang YH, Yan ZZ, Luo SD, Hu JJ, Wu M, Zhao J, et al. Gut microbiota-derived succinate aggravates acute lung injury after intestinal ischaemia/reperfusion in mice. Eur Respir J. 2022. doi:10.1183/13993003.00840-2022.
   Web of Science ®Google Scholar
• Serena C, Ceperuelo-Mallafre V, Keiran N, Queipo-Ortuno MI, Bernal R, Gomez-Huelgas R, Urpi-Sarda M, Sabater M, Pérez-Brocal V, Andrés-Lacueva C, et al. Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota. Isme J. 2018;12:1642–1657. doi:10.1038/s41396-018-0068-2.
   PubMed Web of Science ®Google Scholar
• Pinget GV, Tan JK, Ni D, Taitz J, Daien CI, Mielle J, Moore RJ, Stanley D, Simpson S, King NJC, et al. Dysbiosis in imiquimod-induced psoriasis alters gut immunity and exacerbates colitis development. Cell Rep. 2022;40:111191. doi:10.1016/j.celrep.2022.111191.
   PubMed Web of Science ®Google Scholar
• Zhou X, Liu Y, Xiong X, Chen J, Tang W, He L, Zhang Z, Yin Y, Li F. Intestinal accumulation of microbiota-produced succinate caused by loss of microRnas leads to diarrhea in weanling piglets. Gut Microbes. 2022;14:2091369. doi:10.1080/19490976.2022.2091369.
   PubMed Web of Science ®Google Scholar
• Osaka T, Moriyama E, Arai S, Date Y, Yagi J, Kikuchi J, Tsuneda S. Meta-Analysis of fecal microbiota and metabolites in experimental colitic mice during the inflammatory and healing phases. Nutrients. 2017;9. doi:10.3390/nu9121329.
   PubMed Web of Science ®Google Scholar
• Kushnir MM, Komaromy-Hiller G, Shushan B, Urry FM, Roberts WL. Analysis of dicarboxylic acids by tandem mass spectrometry. High-throughput quantitative measurement of methylmalonic acid in serum, plasma, and urine. Clin Chem. 2001;47:1993–2002. doi:10.1093/clinchem/47.11.1993.
   PubMed Web of Science ®Google Scholar
• Matlac DM, Hadrava Vanova K, Bechmann N, Richter S, Folberth J, Ghayee HK, Ge G-B, Abunimer L, Wesley R, Aherrahrou R, et al. Succinate mediates tumorigenic effects via succinate receptor 1: potential for new targeted treatment strategies in succinate dehydrogenase deficient paragangliomas. Front Endocrinol (Lausanne). 2021;12:589451. doi:10.3389/fendo.2021.589451.
   PubMed Web of Science ®Google Scholar
• Cortes A, Munoz-Antoli C, Esteban JG, Toledo R. Th2 and Th1 responses: clear and hidden sides of immunity against intestinal helminths. Trends Parasitol. 2017;33:678–693. doi:10.1016/j.pt.2017.05.004.
   PubMed Web of Science ®Google Scholar
• Chavez-Galan L, Olleros ML, Vesin D, Garcia I. Much more than M1 and M2 Macrophages, there are also CD169(+) and TCR(+) macrophages. Front Immunol. 2015;6:263. doi:10.3389/fimmu.2015.00263.
   PubMed Web of Science ®Google Scholar
• Kietzmann T, Gorlach A. Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression. Semin Cell Dev Biol. 2005;16:474–486. doi:10.1016/j.semcdb.2005.03.010.
   PubMed Web of Science ®Google Scholar
• Littlewood-Evans A, Sarret S, Apfel V, Loesle P, Dawson J, Zhang J, Muller A, Tigani B, Kneuer R, Patel S, et al. GPR91 senses extracellular succinate released from inflammatory macrophages and exacerbates rheumatoid arthritis. J Exp Med. 2016;213:1655–1662. doi:10.1084/jem.20160061.
   PubMed Web of Science ®Google Scholar
• Rosenberg G, Yehezkel D, Hoffman D, Mattioli CC, Fremder M, Ben-Arosh H, Vainman L, Nissani N, Hen-Avivi S, Brenner S, et al. Host succinate is an activation signal for Salmonella virulence during intracellular infection. Science. 2021;371:400–405. doi:10.1126/science.aba8026.
   PubMed Web of Science ®Google Scholar
• Mizoguchi E, Low D, Ezaki Y, Okada T. Recent updates on the basic mechanisms and pathogenesis of inflammatory bowel diseases in experimental animal models. Intest Res. 2020;18:151–167. doi:10.5217/ir.2019.09154.
   PubMed Web of Science ®Google Scholar
• Dharmasiri S, Garrido-Martin EM, Harris RJ, Bateman AC, Collins JE, Cummings JRF, Sanchez-Elsner T. Human intestinal macrophages are involved in the pathology of both ulcerative colitis and crohn disease. Inflamm Bowel Dis. 2021;27. doi:10.1093/ibd/izab029.
   PubMed Web of Science ®Google Scholar
• Li J, Chen L, Xu X, Fan Y, Xue X, Shen M, Shi X. Targeted combination of antioxidative and anti-inflammatory therapy of rheumatoid arthritis using multifunctional dendrimer-entrapped gold nanoparticles as a platform. Small. 2020;16:e2005661. doi:10.1002/smll.202005661.
   PubMed Web of Science ®Google Scholar
• Shi N, Li N, Duan X, Niu H. Interaction between the gut microbiome and mucosal immune system. Mil Med Res. 2017;4:14. doi:10.1186/s40779-017-0122-9.
   PubMed Web of Science ®Google Scholar
• Na YR, Stakenborg M, Seok SH, Matteoli G. Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD. Nat Rev Gastroenterol Hepatol. 2019;16:531–543. doi:10.1038/s41575-019-0172-4.
   PubMed Web of Science ®Google Scholar
• Mills EL, Kelly B, Logan A, Costa ASH, Varma M, Bryant CE, Tourlomousis P, Däbritz JHM, Gottlieb E, Latorre I, et al. Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell. 2016;167:457–70 e13. doi:10.1016/j.cell.2016.08.064.
   PubMed Web of Science ®Google Scholar
• Park IS, Son M, Ma HW, Kim J, Kim DH, Kim SW, Cheon JH. Succinate-treated macrophages attenuate dextran sodium sulfate colitis in mice. Intest Res. 2020. doi:10.5217/ir.2020.00075.
   Web of Science ®Google Scholar
• Trauelsen M, Rexen Ulven E, Hjorth SA, Brvar M, Monaco C, Frimurer TM, Schwartz TW. Receptor structure-based discovery of non-metabolite agonists for the succinate receptor GPR91. Mol Metab. 2017;6:1585–1596. doi:10.1016/j.molmet.2017.09.005.
   PubMed Web of Science ®Google Scholar
• Keiran N, Ceperuelo-Mallafre V, Calvo E, Hernandez-Alvarez MI, Ejarque M, Nunez-Roa C, Horrillo D, Maymó-Masip E, Rodríguez MM, Fradera R, et al. SUCNR1 controls an anti-inflammatory program in macrophages to regulate the metabolic response to obesity. Nat Immunol. 2019;20:581–592. doi:10.1038/s41590-019-0372-7.
   PubMed Web of Science ®Google Scholar
• Trauelsen M, Hiron TK, Lin D, Petersen JE, Breton B, Husted AS, Hjorth SA, Inoue A, Frimurer TM, Bouvier M, et al. Extracellular succinate hyperpolarizes M2 macrophages through SUCNR1/GPR91-mediated Gq signaling. Cell Rep. 2021;35:109246. doi:10.1016/j.celrep.2021.109246.
   PubMed Web of Science ®Google Scholar
• Liu PS, Wang H, Li X, Chao T, Teav T, Christen S, Di Conza G, Cheng W-C, Chou C-H, Vavakova M, et al. α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol. 2017;18:985–994. doi:10.1038/ni.3796.
   PubMed Web of Science ®Google Scholar
• Parker LC, Prince LR, Sabroe I. Translational mini-review series on Toll-like receptors: networks regulated by Toll-like receptors mediate innate and adaptive immunity. Clin Exp Immunol. 2007;147:199–207. doi:10.1111/j.1365-2249.2006.03203.x.
   PubMed Web of Science ®Google Scholar
• Rubic T, Lametschwandtner G, Jost S, Hinteregger S, Kund J, Carballido-Perrig N, Schwärzler C, Junt T, Voshol H, Meingassner JG, et al. Triggering the succinate receptor GPR91 on dendritic cells enhances immunity. Nat Immunol. 2008;9:1261–1269. doi:10.1038/ni.1657.
   PubMed Web of Science ®Google Scholar
• Borenstein DG, Gibbs CA, Jacobs RP. Gas-liquid chromatographic analysis of synovial fluid. Succinic acid and lactic acid as markers for septic arthritis. Arthritis Rheum. 1982;25:947–953. doi:10.1002/art.1780250806.
   PubMed Web of Science ®Google Scholar
• Kim S, Hwang J, Xuan J, Jung YH, Cha HS, Kim KH, Bahn Y-S. Global metabolite profiling of synovial fluid for the specific diagnosis of rheumatoid arthritis from other inflammatory arthritis. PLoS One. 2014;9:e97501. doi:10.1371/journal.pone.0097501.
   PubMed Web of Science ®Google Scholar
• Saraiva AL, Veras FP, Peres RS, Talbot J, de Lima KA, Luiz JP, Carballido JM, Cunha TM, Cunha FQ, Ryffel B, et al. Succinate receptor deficiency attenuates arthritis by reducing dendritic cell traffic and expansion of Th17 cells in the lymph nodes. Faseb J. 2018:fj201800285. doi:10.1096/fj.201800285
   PubMed Web of Science ®Google Scholar
• Fluck K, Breves G, Fandrey J, Winning S. Hypoxia-inducible factor 1 in dendritic cells is crucial for the activation of protective regulatory T cells in murine colitis. Mucosal Immunol. 2016;9:379–390. doi:10.1038/mi.2015.67.
   PubMed Web of Science ®Google Scholar
• Wood EG, Macdougall CE, Blythe H, Clement M, Colas RA, Dalli J, Marelli-Berg F, Longhi MP. HIF1α activation in dendritic cells under sterile conditions promotes an anti-inflammatory phenotype through accumulation of intracellular lipids. Sci Rep. 2020;10:20825. doi:10.1038/s41598-020-77793-6.
   PubMed Web of Science ®Google Scholar
• Wu JY, Huang TW, Hsieh YT, Wang YF, Yen CC, Lee GL, Yeh C-C, Peng Y-J, Kuo Y-Y, Wen H-T, et al. Cancer-Derived succinate promotes macrophage polarization and cancer metastasis via succinate receptor. Mol Cell. 2020;77:213–27 e5. doi:10.1016/j.molcel.2019.10.023.
   PubMed Web of Science ®Google Scholar
• Fujiwara H, Seike K, Brooks MD, Mathew AV, Kovalenko I, Pal A, Lee H-J, Peltier D, Kim S, Liu C, et al. Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology. Nat Immunol. 2021;22(11):1440–1451. doi:10.1038/s41590-021-01048-3.
   PubMed Web of Science ®Google Scholar
• Chen X, Sunkel B, Wang M, Kang S, Wang T, Gnanaprakasam JNR, Liu L, Cassel TA, Scott DA, Muñoz-Cabello AM, et al. Succinate dehydrogenase/complex II is critical for metabolic and epigenetic regulation of T cell proliferation and inflammation. Sci Immunol. 2022;7:eabm8161. doi:10.1126/sciimmunol.abm8161.
   PubMed Web of Science ®Google Scholar
• Gudgeon N, Munford H, Bishop EL, Hill J, Fulton-Ward T, Bending D, Roberts J, Tennant DA, Dimeloe S. Succinate uptake by T cells suppresses their effector function via inhibition of mitochondrial glucose oxidation. Cell Rep. 2022;40:111193. doi:10.1016/j.celrep.2022.111193.
   PubMed Web of Science ®Google Scholar
• Elia I, Rowe JH, Johnson S, Joshi S, Notarangelo G, Kurmi K, Weiss S, Freeman GJ, Sharpe AH, Haigis MC. Tumor cells dictate anti-tumor immune responses by altering pyruvate utilization and succinate signaling in CD8+ T cells. Cell Metab. 2022;34:1137–50 e6. doi:10.1016/j.cmet.2022.06.008.
   PubMed Web of Science ®Google Scholar
• Hou Q, Ye L, Huang L, Yu Q. The research progress on intestinal stem cells and its relationship with intestinal microbiota. Front Immunol. 2017;8:599. doi:10.3389/fimmu.2017.00599.
   PubMed Web of Science ®Google Scholar
• Gerbe F, van Es JH, Makrini L, Brulin B, Mellitzer G, Robine S, Romagnolo B, Shroyer NF, Bourgaux J-F, Pignodel C, et al. Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium. J Cell Biol. 2011;192:767–780. doi:10.1083/jcb.201010127.
   PubMed Web of Science ®Google Scholar
• Allaire JM, Crowley SM, Law HT, Chang SY, Ko HJ, Vallance BA. The intestinal epithelium: central coordinator of mucosal immunity. Trends Immunol. 2018;39:677–696. doi:10.1016/j.it.2018.04.002.
   PubMed Web of Science ®Google Scholar
• Schneider C, O’leary CE, von Moltke J, Liang HE, Ang QY, Turnbaugh PJ, Radhakrishnan S, Pellizzon M, Ma A, Locksley RM. A metabolite-triggered tuft cell-ILC2 circuit drives small intestinal remodeling. Cell. 2018;174:271–84 e14. doi:10.1016/j.cell.2018.05.014.
   PubMed Web of Science ®Google Scholar
• Nadjsombati MS, McGinty JW, Lyons-Cohen MR, Jaffe JB, DiPeso L, Schneider C, Miller CN, Pollack JL, Nagana Gowda GA, Fontana MF, et al. Detection of succinate by intestinal tuft cells triggers a type 2 innate immune circuit. Immunity. 2018;49:33–41 e7. doi:10.1016/j.immuni.2018.06.016.
   PubMed Web of Science ®Google Scholar
• Banerjee A, Herring CA, Chen B, Kim H, Simmons AJ, Southard-Smith AN, Allaman MM, White JR, Macedonia MC, Mckinley ET, et al. Succinate produced by intestinal microbes promotes specification of tuft cells to suppress ileal inflammation. Gastroenterology. 2020;159:2101–15 e5. doi:10.1053/j.gastro.2020.08.029.
   PubMed Web of Science ®Google Scholar
• Bezencon C, Furholz A, Raymond F, Mansourian R, Metairon S, Le Coutre J, Damak S. Murine intestinal cells expressing Trpm5 are mostly brush cells and express markers of neuronal and inflammatory cells. J Comp Neurol. 2008;509:514–525. doi:10.1002/cne.21768.
   PubMed Web of Science ®Google Scholar
• von Moltke J, Ji M, Liang HE, Locksley RM. Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature. 2016;529:221–225. doi:10.1038/nature16161.
   PubMed Web of Science ®Google Scholar
• Howitt MR, Lavoie S, Michaud M, Blum AM, Tran SV, Weinstock JV, Gallini CA, Redding K, Margolskee RF, Osborne LC, et al. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science. 2016;351:1329–1333. doi:10.1126/science.aaf1648.
   PubMed Web of Science ®Google Scholar
• Gerbe F, Sidot E, Smyth DJ, Ohmoto M, Matsumoto I, Dardalhon V, Cesses P, Garnier L, Pouzolles M, Brulin B, et al. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature. 2016;529:226–230. doi:10.1038/nature16527.
   PubMed Web of Science ®Google Scholar
• Hasnain SZ, Evans CM, Roy M, Gallagher AL, Kindrachuk KN, Barron L, Dickey BF, Wilson MS, Wynn TA, Grencis RK, et al. Muc5ac: a critical component mediating the rejection of enteric nematodes. J Exp Med. 2011;208:893–900. doi:10.1084/jem.20102057.
   PubMed Web of Science ®Google Scholar
• Krimi RB, Kotelevets L, Dubuquoy L, Plaisancie P, Walker F, Lehy T, Desreumaux P, Van Seuningen I, Chastre E, Forgue-Lafitte M-E, et al. Resistin-like molecule β regulates intestinal mucous secretion and curtails TNBS-induced colitis in mice. Inflamm Bowel Dis. 2008;14:931–941. doi:10.1002/ibd.20420.
   PubMed Web of Science ®Google Scholar
• Herbert DR, Yang JQ, Hogan SP, Groschwitz K, Khodoun M, Munitz A, Orekov T, Perkins C, Wang Q, Brombacher F, et al. Intestinal epithelial cell secretion of RELM-β protects against gastrointestinal worm infection. J Exp Med. 2009;206:2947–2957. doi:10.1084/jem.20091268.
   PubMed Web of Science ®Google Scholar
• Wang YH, Angkasekwinai P, Lu N, Voo KS, Arima K, Hanabuchi S, Hippe A, Corrigan CJ, Dong C, Homey B, et al. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC–activated Th2 memory cells. J Exp Med. 2007;204:1837–1847. doi:10.1084/jem.20070406.
   PubMed Web of Science ®Google Scholar
• Halim TY, Steer CA, Matha L, Gold MJ, Martinez-Gonzalez I, McNagny KM, McKenzie AJ, Takei F. Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation. Immunity. 2014;40:425–435. doi:10.1016/j.immuni.2014.01.011.
   PubMed Web of Science ®Google Scholar
• Lei W, Ren W, Ohmoto M, Urban JF Jr., Matsumoto I, Margolskee RF, Jiang P. Activation of intestinal tuft cell-expressed Sucnr1 triggers type 2 immunity in the mouse small intestine. Proc Natl Acad Sci U S A. 2018;115:5552–5557. doi:10.1073/pnas.1720758115.
   PubMed Web of Science ®Google Scholar
• Saz DK, Bonner TP, Karlin M, Saz HJ. Biochemical observations on adult Nippostrongylus brasiliensis. J Parasitol. 1971;57(6):1159–1162. doi:10.2307/3277956.
   PubMed Web of Science ®Google Scholar
• Luo XC, Chen ZH, Xue JB, Zhao DX, Lu C, Li YH, Li S-M, Du Y-W, Liu Q, Wang P, et al. Infection by the parasitic helminth Trichinella spiralis activates a Tas2r-mediated signaling pathway in intestinal tuft cells. Proc Natl Acad Sci U S A. 2019;116:5564–5569. doi:10.1073/pnas.1812901116.
   PubMed Web of Science ®Google Scholar
• Lukes J, Stensvold CR, Jirku-Pomajbikova K, Wegener Parfrey L, Knoll LJ. Are Human Intestinal Eukaryotes Beneficial or Commensals? PLoS Pathog. 2015;11:e1005039. doi:10.1371/journal.ppat.1005039.
   PubMed Web of Science ®Google Scholar
• Chudnovskiy A, Mortha A, Kana V, Kennard A, Ramirez JD, Rahman A, Remark R, Mogno I, Ng R, Gnjatic S, et al. Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome. Cell. 2016;167:444–56 e14. doi:10.1016/j.cell.2016.08.076.
   PubMed Web of Science ®Google Scholar
• Cui H, Chen Y, Li K, Zhan R, Zhao M, Xu Y, Lin Z, Fu Y, He Q, Tang PC, et al. Untargeted metabolomics identifies succinate as a biomarker and therapeutic target in aortic aneurysm and dissection. Eur Heart J. 2021;42:4373–4385. doi:10.1093/eurheartj/ehab605.
   PubMed Web of Science ®Google Scholar
• Chouchani ET, Pell VR, Gaude E, Aksentijevic D, Sundier SY, Robb EL, Logan A, Nadtochiy SM, Ord ENJ, Smith AC, et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014;515:431–435. doi:10.1038/nature13909.
   PubMed Web of Science ®Google Scholar
• Beach TE, Prag HA, Pala L, Logan A, Huang MM, Gruszczyk AV, Martin JL, Mahbubani K, Hamed MO, Hosgood SA, et al. Targeting succinate dehydrogenase with malonate ester prodrugs decreases renal ischemia reperfusion injury. Redox Biol. 2020;36:101640. doi:10.1016/j.redox.2020.101640.
   PubMed Web of Science ®Google Scholar
• Lampropoulou V, Sergushichev A, Bambouskova M, Nair S, Vincent EE, Loginicheva E, Cervantes-Barragan L, Ma X, Huang S-C, Griss T, et al. Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation. Cell Metab. 2016;24:158–166. doi:10.1016/j.cmet.2016.06.004.
   PubMed Web of Science ®Google Scholar
• Swain A, Bambouskova M, Kim H, Andhey PS, Duncan D, Auclair K, Chubukov V, Simons DM, Roddy TP, Stewart KM, et al. Comparative evaluation of itaconate and its derivatives reveals divergent inflammasome and type I interferon regulation in macrophages. Nat Metab. 2020;2:594–602. doi:10.1038/s42255-020-0210-0.
   PubMedGoogle Scholar
• O’neill LAJ, Artyomov MN Itaconate: the poster child of metabolic reprogramming in macrophage function. Nat Rev Immunol 2019; 19:273–281. doi:10.1038/s41577-019-0128-5.
   Google Scholar
• Runtsch MC, Angiari S, Hooftman A, Wadhwa R, Zhang Y, Zheng Y, Spina JS, Ruzek MC, Argiriadi MA, McGettrick AF, et al. Itaconate and itaconate derivatives target JAK1 to suppress alternative activation of macrophages. Cell Metab. 2022;34:487–501 e8. doi:10.1016/j.cmet.2022.02.002.
   PubMed Web of Science ®Google Scholar
• Pajor AM. Molecular cloning and functional expression of a sodium-dicarboxylate cotransporter from human kidney. Am J Physiol. 1996;270:F642–8. doi:10.1152/ajprenal.1996.270.4.F642.
   PubMedGoogle Scholar
• Weerachayaphorn J, Pajor AM. Identification of transport pathways for citric acid cycle intermediates in the human colon carcinoma cell line, Caco-2. Biochim Biophys Acta. 2008;1778:1051–1059. doi:10.1016/j.bbamem.2007.12.013.
   PubMed Web of Science ®Google Scholar
• Ohana E, Shcheynikov N, Moe OW, Muallem S. SLC26A6 and NaDC-1 transporters interact to regulate oxalate and citrate homeostasis. J Am Soc Nephrol. 2013;24:1617–1626. doi:10.1681/ASN.2013010080.
   PubMed Web of Science ®Google Scholar
• Arvans D, Alshaikh A, Bashir M, Weber C, Hassan H. Activation of the PKA signaling pathway stimulates oxalate transport by human intestinal Caco2-BBE cells. Am J Physiol Cell Physiol. 2020;318:C372–9. doi:10.1152/ajpcell.00135.2019.
   PubMed Web of Science ®Google Scholar
• Prag HA, Gruszczyk AV, Huang MM, Beach TE, Young T, Tronci L, Nikitopoulou E, Mulvey JF, Ascione R, Hadjihambi A, et al. Mechanism of succinate efflux upon reperfusion of the ischaemic heart. Cardiovasc Res. 2021;117:1188–1201. doi:10.1093/cvr/cvaa148.
   PubMed Web of Science ®Google Scholar
• Bhuniya D, Umrani D, Dave B, Salunke D, Kukreja G, Gundu J, Naykodi M, Shaikh NS, Shitole P, Kurhade S, et al. Discovery of a potent and selective small molecule hGPR91 antagonist. Bioorg Med Chem Lett. 2011;21:3596–3602. doi:10.1016/j.bmcl.2011.04.091.
   PubMedGoogle Scholar
• Guo Y, Xu F, Thomas SC, Zhang Y, Paul B, Sakilam S, Chae S, Li P, Almeter C, Kamer AR, et al. Targeting the succinate receptor effectively inhibits periodontitis. Cell Rep. 2022;40:111389. doi:10.1016/j.celrep.2022.111389.
   PubMed Web of Science ®Google Scholar
• Vasandan AB, Jahnavi S, Shashank C, Prasad P, Kumar A, Prasanna SJ. Human Mesenchymal stem cells program macrophage plasticity by altering their metabolic status via a PGE2-dependent mechanism. Sci Rep. 2016;6:38308. doi:10.1038/srep38308.
   PubMed Web of Science ®Google Scholar
• Peruzzotti-Jametti L, Bernstock JD, Vicario N, Costa ASH, Kwok CK, Leonardi T, Booty LM, Bicci I, Balzarotti B, Volpe G, et al. Macrophage-Derived extracellular succinate licenses neural stem cells to suppress chronic neuroinflammation. Cell Stem Cell. 2018;22:355–68 e13. doi:10.1016/j.stem.2018.01.020.
   PubMed Web of Science ®Google Scholar
• Yuan Y, Ni S, Zhuge A, Li L, Li B. Adipose-Derived mesenchymal stem cells reprogram M1 macrophage metabolism via PHD2/HIF-1alpha pathway in colitis mice. Front Immunol. 2022;13:859806. doi:10.3389/fimmu.2022.859806.
   PubMed Web of Science ®Google Scholar
• Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C, Kato K, Kato T, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504:446–450. doi:10.1038/nature12721.
   PubMed Web of Science ®Google Scholar
• Zou J, Chassaing B, Singh V, Pellizzon M, Ricci M, Fythe MD, Kumar MV, Gewirtz AT. Fiber-Mediated nourishment of gut microbiota protects against diet-induced obesity by restoring IL-22-mediated colonic health. Cell Host Microbe. 2018;23:41–53 e4. doi:10.1016/j.chom.2017.11.003.
   PubMed Web of Science ®Google Scholar
• Yang W, Yu T, Huang X, Bilotta AJ, Xu L, Lu Y, Sun J, Pan F, Zhou J, Zhang W, et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat Commun. 2020;11:4457. doi:10.1038/s41467-020-18262-6.
   PubMed Web of Science ®Google Scholar
• Nagao-Kitamoto H, Leslie JL, Kitamoto S, Jin C, Thomsson KA, Gillilland MG 3rd, Kuffa P, Goto Y, Jenq RR, Ishii C, et al. Interleukin-22-mediated host glycosylation prevents Clostridioides difficile infection by modulating the metabolic activity of the gut microbiota. Nat Med. 2020;26:608–617. doi:10.1038/s41591-020-0764-0.
   PubMed Web of Science ®Google Scholar
• Hagihara M, Ariyoshi T, Kuroki Y, Eguchi S, Higashi S, Mori T, Nonogaki T, Iwasaki K, Yamashita M, Asai N, et al. Clostridium butyricum enhances colonization resistance against Clostridioides difficile by metabolic and immune modulation. Sci Rep. 2021;11:15007. doi:10.1038/s41598-021-94572-z.
   PubMed Web of Science ®Google Scholar
• Huber-Ruano I, Calvo E, Mayneris-Perxachs J, Rodriguez-Pena MM, Ceperuelo-Mallafre V, Cedo L, Núñez-Roa C, Miro-Blanch J, Arnoriaga-Rodríguez M, Balvay A, et al. Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate. Microbiome. 2022;10:135. doi:10.1186/s40168-022-01306-y.
   PubMed Web of Science ®Google Scholar
• Mills EL, Pierce KA, Jedrychowski MP, Garrity R, Winther S, Vidoni S, Yoneshiro T, Spinelli JB, Lu GZ, Kazak L, et al. Accumulation of succinate controls activation of adipose tissue thermogenesis. Nature. 2018;560:102–106. doi:10.1038/s41586-018-0353-2.
   PubMed Web of Science ®Google Scholar
• Mills EL, Harmon C, Jedrychowski MP, Xiao H, Garrity R, Tran NV, Bradshaw GA, Fu A, Szpyt J, Reddy A, et al. UCP1 governs liver extracellular succinate and inflammatory pathogenesis. Nat Metab. 2021;3:604–617. doi:10.1038/s42255-021-00389-5.
   PubMedGoogle Scholar
• Monfort-Ferre D, Caro A, Menacho M, Marti M, Espina B, Boronat-Toscano A, Nuñez-Roa C, Seco J, Bautista M, Espín E, et al. The gut microbiota metabolite succinate promotes adipose tissue browning in Crohn’s disease. J Crohns Colitis. 2022;16:1571–1583. doi:10.1093/ecco-jcc/jjac069.
   PubMed Web of Science ®Google Scholar