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Research Paper

Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3

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Article: 2281011 | Received 24 May 2023, Accepted 05 Nov 2023, Published online: 11 Dec 2023

References

  • O’Riordan KJ, Collins MK, Moloney GM, Knox EG, Aburto MR, Fulling C, Morley SJ, Clarke G, Schellekens H, Cryan JF. Short chain fatty-acids: microbial metabolites for gut-brain axis signalling. Mol Cell Endocrinol. 2022;456:111572. doi:10.1016/j.mce.2022.111572.
  • Skelly AN, Sato Y, Kearney S, Honda K. Mining the microbiota for microbial and metabolite-based immunotherapies. Nat Rev Immunol. 2019;19(5):305–21. doi:10.1038/s41577-019-0144-5.
  • Chang PV, Hao L, Offermanns S, Medzhitov R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci (USA). 2014;111(6):2247–2252. doi:10.1073/pnas.1322269111.
  • Siddiqui MT, Cresci GAM. The immunomodulatory functions of butyrate. J Inflamm Res. 2021;14:6025–6041. doi:10.2147/JIR.S300989.
  • Rashed R, Valcheva R, Dieleman LA. Manipulation of gut microbiota as a key target for Crohn’s disease. Front Med. 2022;9:887044. doi:10.3389/fmed.2022.887044.
  • Darfeuille-Michaud A, Boudeau J, Bulois P, Neut C, Glasser AL, Barnich N, Bringer MA, Swidsinski A, Beaugerie L, Colombel JF. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn’s disease. Gastroenterology. 2004;127(2):412–421. doi:10.1053/j.gastro.2004.04.061.
  • Wine E, Ossa JC, Gray-Owen SD, Sherman PM. Adherent-invasive Escherichia coli, strain LF82 disrupts apical junctional complexes in polarized epithelia. BMC Microbiol. 2009;9(1):180. doi:10.1186/1471-2180-9-180.
  • Bringer MA, Glasser AL, Tung CH, Meresse S, Darfeuille-Michaud A. The Crohn’s disease-associated adherent-invasive Escherichia coli strain LF82 replicates in mature phagolysosomes within J774 macrophages. Cell Microbiol. 2006;8(3):471–484. doi:10.1111/j.1462-5822.2005.00639.x.
  • Jarry A, Crémet L, Caroff N, Bou-Hanna C, Mussini JM, Reynaud A, Servin AL, Mosnier JF, Liévin-Le Moal V, Laboisse CL. Subversion of human intestinal mucosa innate immunity by a Crohn’s disease-associated E. coli. Mucosal Immunol. 2015;8(3):572–581. doi:10.1038/mi.2014.89.
  • Yang H, Mirsepasi-Lauridsen HC, Struve C, Allaire JM, Sivignon A, Vogl W, Bosman ES, Ma C, Fotovati A, Reid GS, et al. Ulcerative colitis-associated E. coli pathobionts potentiate colitis in susceptible hosts. Gut Microbes. 2020;12(1):1847976. doi:10.1080/19490976.2020.1847976.
  • Negroni A, Costanzo M, Vitali R, Superti F, Bertuccini L, Tinari A, Minelli F, Di Nardo G, Nuti F, Pierdomenico M, et al. Characterization of adherent-invasive Escherichia coli isolated from pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2021;18(5):913–924. doi:10.1002/ibd.21899.
  • Roediger WE. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet. 1980;316(8197):712–715. doi:10.1016/S0140-6736(80)91934-0.
  • Santhanam S, Rajamanickam S, Motamarry A, Ramakrishna BS, Amirtharaj JG, Ramachandran A, Pulimood A, Venkatraman A. Mitochondrial electron transport chain complex dysfunction in the colonic mucosa in ulcerative colitis. Inflamm Bowel Dis. 2012;18(11):2158–2168. doi:10.1002/ibd.22926.
  • Ho GT, Aird RE, Liu B, Boyapati RK, Kennedy NA, Dorward DA, Noble CL, Shimizu T, Carter RN, Chew ETS, et al. MDR1 deficiency impairs mitochondrial homeostasis and promotes intestinal inflammation. Mucosal Immunol. 2018;11(1):120–130. doi:10.1038/mi.2017.31.
  • Alula KM, Jackson DN, Smith AD, Kim DS, Turner K, Odstrcil E, Kaipparettu BA, Dassopoulos T, Venuprasad K, Feagins LA, et al. Targeting mitochondrial damage as a therapeutic for ileal Crohn’s disease. Cells. 2021;10(6):1349. doi:10.3390/cells10061349.
  • Mancini NL, Goudie L, Xu W, Sabouny R, Rajeev S, Wang A, Esquerre N, Rajabi AA, Jayme TS, van Tilburg Bernardes E, et al. Perturbed mitochondrial dynamics is a novel feature of colitis that can be targeted to lessen disease. Cell Mol Gastroenterol Hepatol. 2020;10(2):287–307. doi:10.1016/j.jcmgh.2020.04.004.
  • Stavru F, Bouillaud F, Sartori A, Ricquier D, Cossart P. Listeria monocytogenes transiently alters mitochondrial dynamics during infection. Proc Natl Acad Sci (USA). 2011;108(9):3612–3617. doi:10.1073/pnas.1100126108.
  • McKay DM, Mancini NL, Shearer J, Shutt TE. Perturbed mitochondrial dynamics, an emerging aspect of epithelial-microbe interactions. Am J Physiol Gastrointest Liver Physiol. 2020;318(4):G748–G762. doi:10.1152/ajpgi.00031.2020.
  • Mancini NL, Rajeev S, Jayme TS, Wang A, Keita ÅV, Workentine ML, Hamed S, Söderholm JD, Lopes F, Shutt TE, et al. Crohn’s disease pathobiont adherent-invasive E coli disrupts epithelial mitochondrial networks with implications for gut permeability. Cell Mol Gastroenterol Hepatol. 2021;11(2):551–571. doi:10.1016/j.jcmgh.2020.09.013.
  • Machiels K, Joossens M, Sabino J, De Preter V, Arijs I, Eeckhaut V, Ballet V, Claes K, Van Immerseel F, Verbeke K, et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2014;63(8):1275–1283. doi:10.1136/gutjnl-2013-304833.
  • Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009;249(7244):262–265. doi:10.1038/nature07935.
  • Nazli A, Yang PC, Jury J, Howe K, Watson JL, Söderholm JD, Sherman PM, Perdue MH, McKay DM. Epithelia under metabolic stress perceive commensal bacteria as a threat. Am J Pathol. 2004;164(3):947–957. doi:10.1016/S0002-9440(10)63182-3.
  • Lewis K, Lutgendorff F, Phan V, Söderholm JD, Sherman PM, McKay DM. Enhanced translocation of bacteria across metabolically stressed epithelia is reduced by butyrate. Inflamm Bowel Dis. 2010;16(7):1138–1148. doi:10.1002/ibd.21177.
  • Koch BD, Dorflinger LJ, Schonbrunn A. Pertussis toxin blocks both cyclic AMP-mediated and cyclic AMP-independent actions of somatostatin. Evidence for coupling of Ni to decreases in intracellular free calcium. J Biol Chem. 1985;260(24):260;13138–13145. doi:10.1016/S0021-9258(17)38849-X.
  • Mizuta K, Sasaki H, Zhang Y, Matoba A, Emala CW Sr. The short-chain free fatty acid receptor FFAR3 is expressed and potentiates contraction in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2020;318(6):318;L1248–L1260. doi:10.1152/ajplung.00357.2019.
  • Son SM, Park SJ, Stamatakou E, Vicinanza M, Menzies FM, Rubinsztein DC. Leucine regulates autophagy via acetylation of the mTORC1 component raptor. Nat Commun. 2020;11(1):3148. doi:10.1038/s41467-020-16886-2.
  • Donohoe DR, Garge N, Zhang X, Sun W, O’Connell TM, Bunger MK, Bultman SJ. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metabol. 2011;13(5):5117–5526. doi:10.1016/j.cmet.2011.02.018.
  • Mikami D, Kobayashi M, Uwada J, Yazawa T, Kamiyama K, Nishimori K, Nishikawa Y, Nishikawa S, Yokoi S, Taniguchi T, et al. AR420626, a selective agonist of GPR41/FFA3, suppresses growth of hepatocellular carcinoma cells by inducing apoptosis via HDAC inhibition. Ther Adv Med Oncol. 2020;12:1758835920913432. doi:10.1177/1758835920913432.
  • Bishop SL, Drikic M, Wacker S, Chen YK, Kozrskyj AL, Lewis IA. Moving beyond descriptive studies: harnessing metabolomics to elucidate the molecular mechanisms underpinning host-microbiome phenotypes. Mucosal Immunol. 2020;15(6):1071–1084. doi:10.1038/s41385-022-00553-4.
  • Rydzak T, Groves RA, Zhang R, Aburashed R, Pushpkar R, Mapor M, Lewis IA. Metabolic preference assay for rapid diagnosis of bloodstream infections. Nat Commun. 2020;13(1):2332. doi:10.1038/s41467-022-30048-6.
  • Brown K, Thomson CA, Wacker S, Drikic M, Groves R, Fan V, Lewis IA, McCoy KD. Microbiota alters the metabolome in an age- and sex-dependent manner in mice. Nat Commun. 2023;14(1):1348. doi:10.1038/s41467-023-37055-1.
  • Lu W, Clasquin MF, Melamud E, Amador-Noguez D, Caudy AA, Rabinowitz JD. Metabolomic analysis via reversed-phase ion-pairing liquid chromatography coupled to a stand alone orbitrap mass spectrometer. Anal Chem. 2010;82(8):3212–3221. doi:10.1021/ac902837x.
  • Melamud E, Vastag L, Rabinowitz JD. Metabolic analysis and visualization engine in LC-MS data. Physiol Rev. 2016;176:139–148.
  • Chen KH, Dasgupta A, Lin J, Potus F, Bonnet S, Iremonger J, Fu J, Mewburn J, Wu D, Dunham-Snary K, et al. Epigenetic dysregulation of the dynamin-related protein 1 binding partners MiD49 and MiD51 increases mitotic mitochondrial fission and promotes pulmonary arterial hypertension: mechanistic and therapeutic implications. Circulation. 2018;138(3):287–304. doi:10.1161/CIRCULATIONAHA.117.031258.
  • Chojnacki AK, Navaneetha Krishnan S, Jijon H, Shutt TE, Colarusso P, McKay DM. Tissue imaging reveals disruption of epithelial mitochondrial networks and loss of mitochondria-associated cytochrome-c in inflamed human and mouse colon. Mitochondrion. 2023;68:44–59. doi:10.1016/j.mito.2022.10.004.
  • Sabouny R, Wong R, Lee-Glover L, Greenway SC, Sinasac DS, Care4Rare Canada, Khan A, Shutt TE. Characterization of the C584R variant in the mtDNA depletion syndrome gene FBXL4, reveals a novel role for FBXL4 as a regulator of mitochondrial fusion. Biochim Biophys Acta Mol Basis Dis. 2019;1865(11):165536. doi:10.1016/j.bbadis.2019.165536.
  • Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101–1108. doi:10.1038/nprot.2008.73.
  • Rooney JP, Ryde IT, Sanders LH, Howlett H, Colton MD, Germ KE, Mayer GD, Greenamyre JT, Meyer JN. PCR based determination of mitochondrial DNA copy number in multiple species. Methods Mol Biol. 2015;1241:23–38.
  • Parada Venegas D, De la Fuente MK, Landskron G, González MJ, Quera R, Dijkstra G, Harmsen HJM, Faber KN, Hermoso MA. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol. 2019;10:277. doi:10.3389/fimmu.2019.00277.
  • Elatrech I, Marzaioli V, Boukemara H, Bournier O, Neut C, Darfeuille-Michaud A, Luis J, Dubuquoy L, El-Benna J, My-Chan Dang P, et al. Escherichia coli LF82 differentially regulates ROS production and mucin expression in intestinal epithelial T84 cells: implication of NOX1. Inflamm Bowel Dis. 2015;21(5):1018–1026. doi:10.1097/MIB.0000000000000365.
  • Heller S, Penrose HM, Cable C, Biswas D, Nakhoul H, Baddoo M, Flemington E, Crawford SE, Savkovic SD. Reduced mitochondrial activity in colonocytes facilitates AMPKα2-dependent inflammation. FASEB J. 2017;31(5):2013–2025. doi:10.1096/fj.201600976R.
  • Zheng L, Kelly CJ, Battista KD, Schaefer R, Lanis JM, Alexeev EE, Wang RX, Onyiah JC, Kominsky DJ, Colgan SP. Microbial-derived butyrate promotes epithelial barrier function through IL-10 receptor–dependent repression of claudin-2. J Immunol. 2017;199(8):2976–2984. doi:10.4049/jimmunol.1700105.
  • Rath E, Haller D. Intestinal epithelial cell metabolism at the interface of microbial dysbiosis and tissue injury. Mucosal Immunol. 2022;15(4):595–604. doi:10.1038/s41385-022-00514-x.
  • Sharkey KA, Beck PL, McKay DM. Neuroimmunophysiology of the gut: advances and emerging concepts focusing on the epithelium. Nat Rev Gastroenterol Hepatol. 2018;15(12):765–784. doi:10.1038/s41575-018-0051-4.
  • Carvalho F, Spier A, Chaze T, Matondo M, Cossart P, Stavru F. Listeria monocytogenes exploits mitochondrial contact site and cristae organizing system complex subunit Mic10 to promote mitochondrial fragmentation and cellular infection. mBio. 2020;11(1):11;e0317–19. doi:10.1128/mBio.03171-19.
  • Riviere A, Selak M, Lantin D, Leroy F, De Vuyst L. Bifidobacteria and butyrate-producing colon bacteria: importance and strategies for their stimulation in the human gut. Front Microbiol. 2016;7:979. doi:10.3389/fmicb.2016.00979.
  • Chen J, Vitetta L. The role of butyrate in attenuating pathobiont-induced hyperinflammation. Immune Netw. 2020;20(2):e15. doi:10.4110/in.2020.20.e15.
  • Fernando MR, Saxena A, Reyes JL, McKay DM. Butyrate enhances antibacterial effects while suppressing other features of alternative activation in IL-4-induced macrophages. Am J Physiol Gastrointest Liver Physiol. 2016;310(10):G822–G831. doi:10.1152/ajpgi.00440.2015.
  • Schulthess J, Pandey S, Capitani M, Rue-Albrecht KC, Arnold I, Franchini F, Chomka A, Ilott NE, Johnston DGW, Pires E, et al. The short chain fatty acid butyrate imprints an antimicrobial program in macrophages. Immunity. 2019;50(2):432–445.e7. doi:10.1016/j.immuni.2018.12.018.
  • Zhang S, Dogan B, Guo C, Herlekar D, Stewart K, Scherl EJ, Simpson KW. Short chain fatty acids modulate the growth and virulence of pathosymbiont Escherichia coli and host response. Antibiotics. 2020;9(8):462. doi:10.3390/antibiotics9080462.
  • Nagai T, Abe A, Sasakawa C. Targeting of enteropathogenic Escherichia coli EspF to host mitochondria is essential for bacterial pathogenesis: critical role of the 16th leucine residue in EspF. J Biol Chem. 2005;280(4):2998–3011. doi:10.1074/jbc.M411550200.
  • Deo P, Chow SH, Hay ID, Kleifeld O, Costin A, Elgass KD, Jiang JH, Ramm G, Gabriel K, Dougan G, et al. Outer membrane vesicles from Neisseria gonorrhoeae target PorB to mitochondria and induce apoptosis. PLoS Pathog. 2018;14(3):e1006945. doi:10.1371/journal.ppat.1006945.
  • Lu Y, Rafiq A, Zhang Z, Aslani F, Fijak M, Lei T, Wang M, Kumar S, Klug J, Bergmann M, et al. Uropathogenic Escherichia coli virulence factor hemolysin a causes programmed cell necrosis by altering mitochondrial dynamics. FASEB J. 2018;32(8):4107–4120. doi:10.1096/fj.201700768R.
  • Lu YT, Li LZ, Yang YL, Yin X, Liu Q, Zhang L, Liu K, Liu B, Li J, Qi LW. Succinate induces aberrant mitochondrial fission in cardiomyocytes through GPR91 signaling. Cell Death Disease. 2018;9(6):672. doi:10.1038/s41419-018-0708-5.
  • Zhang Y, Yu B, Yu J, Zheng P, Huang Z, Luo Y, Luo J, Mao X, Yan H, He J, et al. Butyrate promotes slow-twitch myofiber formation and mitochondrial biogenesis in finishing pigs via inducing specific microRnas and PGC-1α expression. J Animal Sci. 2019;97(8):3180–3192. doi:10.1093/jas/skz187.
  • Li X, Wang C, Zhu J, Lin Q, Yu M, Wen J, Feng J, Hu C. Sodium butyrate ameliorates oxidative stress-induced intestinal epithelial barrier injury and mitochondrial damage through AMPK-mitophagy pathway. Oxid Med Cell Longev. 2002;2022:3745135. doi:10.1155/2022/3745135.
  • Li RW, Li C. Butyrate induces profound changes in gene expression related to multiple signal pathways in bovine kidney epithelial cells. Bmc Genom. 2006;7(1):234. doi:10.1186/1471-2164-7-234.
  • Cowell RM, Talati P, Blake KR, Meador-Woodruff JH, Russell JW. Identification of novel targets for PGC-1α and histone deacetylase inhibitors in neuroblastoma cells. Biochem Biophys Res Commun. 2009;379(2):578–582. doi:10.1016/j.bbrc.2008.12.109.
  • Colgan SP, Wang RX, Hall CHT, Bhagavatula G, Lee JS. Revisiting the “starved gut” hypothesis in inflammatory bowel disease. Immunometabolism. 2023;5(1):e0016. doi:10.1097/IN9.0000000000000016.
  • Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci (USA). 2008;105(43):16767–16772. doi:10.1073/pnas.0808567105.
  • Mohamed Elfadil O, Mundi MS, Abdelmagid MG, Patel A, Patel N, Martindale R. Butyrate: more than a short chain fatty acid. Curr Nutr Rep. 2023;12(2):255–262. in press. doi:10.1007/s13668-023-00461-4.
  • Ang Z, Xiong D, Wu M, Ding JL. FFAR2-FFAR3 receptor heteromerization modulates short-chain fatty acid sensing. FASEB J. 2018;32(1):289–303. doi:10.1096/fj.201700252RR.
  • Michi AN, Yipp BG, Dufour A, Lopes F, Proud D. PGC-1α mediates a metabolic host defense response in human airway epithelium during rhinovirus infections. Nat Commun. 2021;12(1):3669. doi:10.1038/s41467-021-23925-z.
  • Thibault R, De Coppet P, Daly K, Bourreille A, Cuff M, Bonnet C, Mosnier JF, Galmiche JP, Shirazi-Beechey S, Segain JP. Down-regulation of the monocarboxylate transporter 1 is involved in butyrate deficiency during intestinal inflammation. Gastroenterology. 2007;133(6):1916–1927. doi:10.1053/j.gastro.2007.08.041.