{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:01:45Z","timestamp":1785456105444,"version":"3.56.0"},"reference-count":99,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":62,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100011684","name":"Crohn's and Colitis Foundation","doi-asserted-by":"publisher","award":["929250"],"award-info":[{"award-number":["929250"]}],"id":[{"id":"10.13039\/100011684","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK2BX006088"],"award-info":[{"award-number":["IK2BX006088"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK2BX005710"],"award-info":[{"award-number":["IK2BX005710"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK6BX005384"],"award-info":[{"award-number":["IK6BX005384"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK6BX006475"],"award-info":[{"award-number":["IK6BX006475"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32GM149361"],"award-info":[{"award-number":["T32GM149361"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K01DK129410"],"award-info":[{"award-number":["K01DK129410"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K08DK138279"],"award-info":[{"award-number":["K08DK138279"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK095491"],"award-info":[{"award-number":["R01DK095491"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI136520"],"award-info":[{"award-number":["R01AI136520"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Microbiome"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The gastrointestinal tract is home to trillions of microorganisms that interact with their host in profound ways. One mechanism by which these microbes interact with their eukaryotic host is through the establishment of \u201cphysiologic hypoxia\u201d in the intestinal mucosa, which has been shown to promote gut barrier function and homeostasis in a hypoxia-inducible factor (HIF)-dependent manner. The association between HIF and intestinal homeostasis has been long understood, as activation of HIF signaling has been shown to promote barrier function both in vitro and in vivo. Although it has been previously established that pathogenic bacteria regulate HIF stabilization and activity in the intestinal epithelium independent of short-chain fatty acid metabolism, it is not clear whether this activity extends to noninfectious and\/or commensal bacterial species.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Here, we demonstrate that nonpathogenic, commensal strains of\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      stabilize HIF in intestinal epithelial cells in vitro. Further, we show that HIF is transcriptionally active in epithelia and drives a \u201cpro-barrier\u201d transcriptional program. This property was found to be dependent on bacterial aerobic respiration, as genetic elimination of\n                      <jats:italic>E. coli<\/jats:italic>\n                      aerobic respiration abolished HIF stabilization and the subsequent transcriptional phenotype. Finally, we observed stabilization of tissue HIF-1\u03b1 in vivo using antibiotic-treated mice colonized with wild-type, but not respiration-deficient,\n                      <jats:italic>E. coli<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate a novel ability for commensal\n                      <jats:italic>E. coli<\/jats:italic>\n                      to regulate intestinal homeostasis through activation of HIF and suggest that this mechanism might be a major component of the interaction between facultative anaerobes and the intestinal epithelium in the gut. In addition, we hypothesize that consumption of oxygen by enteric bacteria might be leveraged as a novel therapeutic to combat intestinal inflammation, such as that observed during inflammatory bowel disease (IBD).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40168-026-02431-8","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T02:04:39Z","timestamp":1780106679000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic host-microbe crosstalk in stabilization of epithelial HIF"],"prefix":"10.1186","volume":"14","author":[{"given":"Alexander S.","family":"Dowdell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Roer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetha","family":"Bhagavatula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Cartwright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel H.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A.","family":"Countess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel D.","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Scott","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calen A.","family":"Steiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah T.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary F.","family":"Villamaria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nichole","family":"Welch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey S.","family":"Worledge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liheng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Vazquez-Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean P.","family":"Colgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"issue":"5","key":"2431_CR1","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/S2468-1253(23)00003-1","volume":"8","author":"J Burisch","year":"2023","unstructured":"Burisch J, Zhao M, Odes S, De Cruz P, Vermeire S, Bernstein CN, et al. The cost of inflammatory bowel disease in high-income settings: a Lancet Gastroenterology & Hepatology Commission. Lancet Gastroenterol Hepatol. 2023;8(5):458\u201392. https:\/\/doi.org\/10.1016\/S2468-1253(23)00003-1.","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"10014","key":"2431_CR2","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/S0140-6736(15)00465-1","volume":"387","author":"I Cleynen","year":"2016","unstructured":"Cleynen I, Boucher G, Jostins L, Schumm LP, Zeissig S, Ahmad T, et al. Inherited determinants of Crohn\u2019s disease and ulcerative colitis phenotypes: a genetic association study. Lancet. 2016;387(10014):156\u201367. https:\/\/doi.org\/10.1016\/S0140-6736(15)00465-1.","journal-title":"Lancet"},{"issue":"27","key":"2431_CR3","doi-asserted-by":"publisher","first-page":"2652","DOI":"10.1056\/NEJMra2002697","volume":"383","author":"JT Chang","year":"2020","unstructured":"Chang JT. Pathophysiology of inflammatory bowel diseases. N Engl J Med. 2020;383(27):2652\u201364. https:\/\/doi.org\/10.1056\/NEJMra2002697.","journal-title":"N Engl J Med"},{"issue":"6","key":"2431_CR4","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1056\/NEJMra020831","volume":"347","author":"DK Podolsky","year":"2002","unstructured":"Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347(6):417\u201329. https:\/\/doi.org\/10.1056\/NEJMra020831.","journal-title":"N Engl J Med"},{"issue":"5","key":"2431_CR5","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.3748\/wjg.v20.i5.1165","volume":"20","author":"L Antoni","year":"2014","unstructured":"Antoni L, Nuding S, Wehkamp J, Stange EF. Intestinal barrier in inflammatory bowel disease. World J Gastroenterol. 2014;20(5):1165\u201379. https:\/\/doi.org\/10.3748\/wjg.v20.i5.1165.","journal-title":"World J Gastroenterol"},{"issue":"2","key":"2431_CR6","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/s41575-020-00399-w","volume":"18","author":"S Mehandru","year":"2021","unstructured":"Mehandru S, Colombel JF. The intestinal barrier, an arbitrator turned provocateur in IBD. Nat Rev Gastroenterol Hepatol. 2021;18(2):83\u20134. https:\/\/doi.org\/10.1038\/s41575-020-00399-w.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"6","key":"2431_CR7","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1053\/j.gastro.2020.08.005","volume":"159","author":"W Turpin","year":"2020","unstructured":"Turpin W, Lee SH, Raygoza Garay JA, Madsen KL, Meddings JB, Bedrani L, et al. Increased intestinal permeability is associated with later development of Crohn\u2019s disease. Gastroenterology. 2020;159(6):2092-100 e5. https:\/\/doi.org\/10.1053\/j.gastro.2020.08.005.","journal-title":"Gastroenterology"},{"issue":"2","key":"2431_CR8","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1053\/j.gastro.2022.10.014","volume":"164","author":"T Rath","year":"2023","unstructured":"Rath T, Atreya R, Bodenschatz J, Uter W, Geppert CE, Vitali F, et al. Intestinal barrier healing is superior to endoscopic and histologic remission for predicting major adverse outcomes in inflammatory bowel disease: the prospective ERIca Trial. Gastroenterology. 2023;164(2):241\u201355. https:\/\/doi.org\/10.1053\/j.gastro.2022.10.014.","journal-title":"Gastroenterology"},{"issue":"9","key":"2431_CR9","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1080\/17474124.2017.1343143","volume":"11","author":"M Vancamelbeke","year":"2017","unstructured":"Vancamelbeke M, Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol. 2017;11(9):821\u201334. https:\/\/doi.org\/10.1080\/17474124.2017.1343143.","journal-title":"Expert Rev Gastroenterol Hepatol"},{"issue":"3","key":"2431_CR10","doi-asserted-by":"publisher","first-page":"C866","DOI":"10.1152\/ajpcell.00227.2022","volume":"323","author":"CA Steiner","year":"2022","unstructured":"Steiner CA, Cartwright IM, Taylor CT, Colgan SP. Hypoxia-inducible factor as a bridge between healthy barrier function, wound healing, and fibrosis. Am J Physiol Cell Physiol. 2022;323(3):C866\u201378. https:\/\/doi.org\/10.1152\/ajpcell.00227.2022.","journal-title":"Am J Physiol Cell Physiol"},{"issue":"3","key":"2431_CR11","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/s41573-023-00848-6","volume":"23","author":"X Yuan","year":"2024","unstructured":"Yuan X, Ruan W, Bobrow B, Carmeliet P, Eltzschig HK. Targeting hypoxia-inducible factors: therapeutic opportunities and challenges. Nat Rev Drug Discov. 2024;23(3):175\u2013200. https:\/\/doi.org\/10.1038\/s41573-023-00848-6.","journal-title":"Nat Rev Drug Discov"},{"issue":"5","key":"2431_CR12","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/s41580-020-0227-y","volume":"21","author":"P Lee","year":"2020","unstructured":"Lee P, Chandel NS, Simon MC. Cellular adaptation to hypoxia through hypoxia inducible factors and beyond. Nat Rev Mol Cell Biol. 2020;21(5):268\u201383. https:\/\/doi.org\/10.1038\/s41580-020-0227-y.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"6","key":"2431_CR13","doi-asserted-by":"publisher","first-page":"C350","DOI":"10.1152\/ajpcell.00191.2015","volume":"309","author":"L Zheng","year":"2015","unstructured":"Zheng L, Kelly CJ, Colgan SP. Physiologic hypoxia and oxygen homeostasis in the healthy intestine. A review in the theme: cellular responses to hypoxia. Am J Physiol Cell Physiol. 2015;309(6):C350\u201360. https:\/\/doi.org\/10.1152\/ajpcell.00191.2015.","journal-title":"Am J Physiol Cell Physiol"},{"issue":"8","key":"2431_CR14","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1172\/JCI21086","volume":"114","author":"J Karhausen","year":"2004","unstructured":"Karhausen J, Furuta GT, Tomaszewski JE, Johnson RS, Colgan SP, Haase VH. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J Clin Invest. 2004;114(8):1098\u2013106. https:\/\/doi.org\/10.1172\/JCI21086.","journal-title":"J Clin Invest"},{"issue":"1","key":"2431_CR15","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1053\/j.gastro.2007.10.012","volume":"134","author":"EP Cummins","year":"2008","unstructured":"Cummins EP, Seeballuck F, Keely SJ, Mangan NE, Callanan JJ, Fallon PG, et al. The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis. Gastroenterology. 2008;134(1):156\u201365. https:\/\/doi.org\/10.1053\/j.gastro.2007.10.012.","journal-title":"Gastroenterology"},{"issue":"1","key":"2431_CR16","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1053\/j.gastro.2007.09.033","volume":"134","author":"A Robinson","year":"2008","unstructured":"Robinson A, Keely S, Karhausen J, Gerich ME, Furuta GT, Colgan SP. Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition. Gastroenterology. 2008;134(1):145\u201355. https:\/\/doi.org\/10.1053\/j.gastro.2007.09.033.","journal-title":"Gastroenterology"},{"issue":"3","key":"2431_CR17","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1053\/j.gastro.2007.12.008","volume":"134","author":"H Hartmann","year":"2008","unstructured":"Hartmann H, Eltzschig HK, Wurz H, Hantke K, Rakin A, Yazdi AS, et al. Hypoxia-independent activation of HIF-1 by Enterobacteriaceae and their siderophores. Gastroenterology. 2008;134(3):756\u201367. https:\/\/doi.org\/10.1053\/j.gastro.2007.12.008.","journal-title":"Gastroenterology"},{"issue":"7","key":"2431_CR18","doi-asserted-by":"publisher","first-page":"e11576","DOI":"10.1371\/journal.pone.0011576","volume":"5","author":"N Werth","year":"2010","unstructured":"Werth N, Beerlage C, Rosenberger C, Yazdi AS, Edelmann M, Amr A, et al. Activation of hypoxia inducible factor 1 is a general phenomenon in infections with human pathogens. PLoS ONE. 2010;5(7):e11576. https:\/\/doi.org\/10.1371\/journal.pone.0011576.","journal-title":"PLoS ONE"},{"issue":"13","key":"2431_CR19","doi-asserted-by":"publisher","first-page":"111409","DOI":"10.1016\/j.celrep.2022.111409","volume":"40","author":"AS Dowdell","year":"2022","unstructured":"Dowdell AS, Cartwright IM, Kitzenberg DA, Kostelecky RE, Mahjoob O, Saeedi BJ, et al. Essential role for epithelial HIF-mediated xenophagy in control of Salmonella infection and dissemination. Cell Rep. 2022;40(13):111409. https:\/\/doi.org\/10.1016\/j.celrep.2022.111409.","journal-title":"Cell Rep"},{"issue":"20","key":"2431_CR20","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.1091\/mbc.E20-05-0291","volume":"31","author":"AS Dowdell","year":"2020","unstructured":"Dowdell AS, Cartwright IM, Goldberg MS, Kostelecky R, Ross T, Welch N, et al. The HIF target ATG9A is essential for epithelial barrier function and tight junction biogenesis. Mol Biol Cell. 2020;31(20):2249\u201358. https:\/\/doi.org\/10.1091\/mbc.E20-05-0291.","journal-title":"Mol Biol Cell"},{"issue":"49","key":"2431_CR21","doi-asserted-by":"publisher","first-page":"19820","DOI":"10.1073\/pnas.1302840110","volume":"110","author":"LE Glover","year":"2013","unstructured":"Glover LE, Bowers BE, Saeedi B, Ehrentraut SF, Campbell EL, Bayless AJ, et al. Control of creatine metabolism by HIF is an endogenous mechanism of barrier regulation in colitis. Proc Natl Acad Sci U S A. 2013;110(49):19820\u20135. https:\/\/doi.org\/10.1073\/pnas.1302840110.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"2431_CR22","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1038\/nprot.2010.43","volume":"5","author":"L Young","year":"2010","unstructured":"Young L, Sung J, Stacey G, Masters JR. Detection of Mycoplasma in cell cultures. Nat Protoc. 2010;5(5):929\u201334. https:\/\/doi.org\/10.1038\/nprot.2010.43.","journal-title":"Nat Protoc"},{"issue":"1","key":"2431_CR23","doi-asserted-by":"publisher","first-page":"2014772","DOI":"10.1080\/19490976.2021.2014772","volume":"14","author":"WH Wu","year":"2022","unstructured":"Wu WH, Kim M, Chang LC, Assie A, Saldana-Morales FB, Zegarra-Ruiz DF, et al. Interleukin-1\u03b2 secretion induced by mucosa-associated gut commensal bacteria promotes intestinal barrier repair. Gut Microbes. 2022;14(1):2014772. https:\/\/doi.org\/10.1080\/19490976.2021.2014772.","journal-title":"Gut Microbes"},{"issue":"10","key":"2431_CR24","doi-asserted-by":"publisher","first-page":"6202","DOI":"10.4049\/jimmunol.172.10.6202","volume":"172","author":"A Vazquez-Torres","year":"2004","unstructured":"Vazquez-Torres A, Vallance BA, Bergman MA, Finlay BB, Cookson BT, Jones-Carson J, et al. Toll-like receptor 4 dependence of innate and adaptive immunity to Salmonella: importance of the Kupffer cell network. J Immunol. 2004;172(10):6202\u20138. https:\/\/doi.org\/10.4049\/jimmunol.172.10.6202.","journal-title":"J Immunol"},{"issue":"5","key":"2431_CR25","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1093\/abbs\/gmab036","volume":"53","author":"Q Li","year":"2021","unstructured":"Li Q, Sun B, Chen J, Zhang Y, Jiang Y, Yang S. A modified pCas\/pTargetF system for CRISPR-Cas9-assisted genome editing in Escherichia coli. Acta Biochim Biophys Sin. 2021;53(5):620\u20137. https:\/\/doi.org\/10.1093\/abbs\/gmab036.","journal-title":"Acta Biochim Biophys Sin"},{"issue":"W1","key":"2431_CR26","doi-asserted-by":"publisher","first-page":"W171","DOI":"10.1093\/nar\/gkz365","volume":"47","author":"K Labun","year":"2019","unstructured":"Labun K, Montague TG, Krause M, Torres Cleuren YN, Tjeldnes H, Valen E. CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing. Nucleic Acids Res. 2019;47(W1):W171\u20134. https:\/\/doi.org\/10.1093\/nar\/gkz365.","journal-title":"Nucleic Acids Res"},{"issue":"W1","key":"2431_CR27","doi-asserted-by":"publisher","first-page":"W272","DOI":"10.1093\/nar\/gkw398","volume":"44","author":"K Labun","year":"2016","unstructured":"Labun K, Montague TG, Gagnon JA, Thyme SB, Valen E. CHOPCHOP v2: a web tool for the next generation of CRISPR genome engineering. Nucleic Acids Res. 2016;44(W1):W272\u20136. https:\/\/doi.org\/10.1093\/nar\/gkw398.","journal-title":"Nucleic Acids Res"},{"issue":"Web Server issu","key":"2431_CR28","doi-asserted-by":"publisher","first-page":"W401","DOI":"10.1093\/nar\/gku410","volume":"42","author":"TG Montague","year":"2014","unstructured":"Montague TG, Cruz JM, Gagnon JA, Church GM, Valen E. CHOPCHOP: a CRISPR\/Cas9 and TALEN web tool for genome editing. Nucleic Acids Res. 2014;42(Web Server issue):W401\u20137. https:\/\/doi.org\/10.1093\/nar\/gku410.","journal-title":"Nucleic Acids Res"},{"key":"2431_CR29","unstructured":"Bio-Rad. Gene Pulser Xcell Electroporation System Instruction Manual. https:\/\/www.bio-rad.com\/webroot\/web\/pdf\/lsr\/literature\/4006217A.pdf. Accessed."},{"issue":"1","key":"2431_CR30","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1021\/acssynbio.0c00466","volume":"10","author":"A Kan","year":"2021","unstructured":"Kan A, Gelfat I, Emani S, Praveschotinunt P, Joshi NS. Plasmid vectors for in vivo selection-free use with the probiotic E. coli Nissle 1917. ACS Synth Biol. 2021;10(1):94\u2013106. https:\/\/doi.org\/10.1021\/acssynbio.0c00466.","journal-title":"ACS Synth Biol"},{"issue":"24","key":"2431_CR31","doi-asserted-by":"publisher","first-page":"7561","DOI":"10.1128\/AEM.00880-08","volume":"74","author":"VA Portnoy","year":"2008","unstructured":"Portnoy VA, Herrgard MJ, Palsson BO. Aerobic fermentation of D-glucose by an evolved cytochrome oxidase-deficient Escherichia coli strain. Appl Environ Microbiol. 2008;74(24):7561\u20139. https:\/\/doi.org\/10.1128\/AEM.00880-08.","journal-title":"Appl Environ Microbiol"},{"issue":"2","key":"2431_CR32","doi-asserted-by":"publisher","first-page":"2267706","DOI":"10.1080\/19490976.2023.2267706","volume":"15","author":"A Ornelas","year":"2023","unstructured":"Ornelas A, Welch N, Countess JA, Zhou L, Wang RX, Dowdell AS, et al. Mimicry of microbially-derived butyrate reveals templates for potent intestinal epithelial HIF stabilizers. Gut Microbes. 2023;15(2):2267706. https:\/\/doi.org\/10.1080\/19490976.2023.2267706.","journal-title":"Gut Microbes"},{"issue":"15","key":"2431_CR33","doi-asserted-by":"publisher","first-page":"4509","DOI":"10.1128\/JB.183.15.4509-4516.2001","volume":"183","author":"P Duwat","year":"2001","unstructured":"Duwat P, Sourice S, Cesselin B, Lamberet G, Vido K, Gaudu P, et al. Respiration capacity of the fermenting bacterium Lactococcus lactis and its positive effects on growth and survival. J Bacteriol. 2001;183(15):4509\u201316. https:\/\/doi.org\/10.1128\/JB.183.15.4509-4516.2001.","journal-title":"J Bacteriol"},{"issue":"7","key":"2431_CR34","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676\u201382. https:\/\/doi.org\/10.1038\/nmeth.2019.","journal-title":"Nat Methods"},{"issue":"1","key":"2431_CR35","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1006\/abio.1995.1126","volume":"225","author":"P Chomczynski","year":"1995","unstructured":"Chomczynski P, Mackey K. Substitution of chloroform by bromo-chloropropane in the single-step method of RNA isolation. Anal Biochem. 1995;225(1):163\u20134. https:\/\/doi.org\/10.1006\/abio.1995.1126.","journal-title":"Anal Biochem"},{"issue":"Database issue","key":"2431_CR36","doi-asserted-by":"publisher","first-page":"D1144","DOI":"10.1093\/nar\/gkr1013","volume":"40","author":"X Wang","year":"2012","unstructured":"Wang X, Spandidos A, Wang H, Seed B. PrimerBank: a PCR primer database for quantitative gene expression analysis, 2012 update. Nucleic Acids Res. 2012;40(Database issue):D1144\u20139. https:\/\/doi.org\/10.1093\/nar\/gkr1013.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"2431_CR37","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1186\/s12859-021-04306-1","volume":"22","author":"A Untergasser","year":"2021","unstructured":"Untergasser A, Ruijter JM, Benes V, van den Hoff MJB. Web-based LinRegPCR: application for the visualization and analysis of (RT)-qPCR amplification and melting data. BMC Bioinformatics. 2021;22(1):398. https:\/\/doi.org\/10.1186\/s12859-021-04306-1.","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"2431_CR38","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.cell.2018.05.009","volume":"174","author":"ZE Walton","year":"2018","unstructured":"Walton ZE, Patel CH, Brooks RC, Yu Y, Ibrahim-Hashim A, Riddle M, et al. Acid suspends the circadian clock in hypoxia through inhibition of mTOR. Cell. 2018;174(1):72-87 e32. https:\/\/doi.org\/10.1016\/j.cell.2018.05.009.","journal-title":"Cell"},{"key":"2431_CR39","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/978-1-60327-032-8_16","volume":"431","author":"O Steele-Mortimer","year":"2008","unstructured":"Steele-Mortimer O. Infection of epithelial cells with Salmonella enterica. Methods Mol Biol. 2008;431:201\u201311. https:\/\/doi.org\/10.1007\/978-1-60327-032-8_16.","journal-title":"Methods Mol Biol"},{"issue":"5","key":"2431_CR40","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1016\/j.chom.2015.03.005","volume":"17","author":"CJ Kelly","year":"2015","unstructured":"Kelly CJ, Zheng L, Campbell EL, Saeedi B, Scholz CC, Bayless AJ, et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe. 2015;17(5):662\u201371. https:\/\/doi.org\/10.1016\/j.chom.2015.03.005.","journal-title":"Cell Host Microbe"},{"issue":"1","key":"2431_CR41","doi-asserted-by":"publisher","first-page":"1938380","DOI":"10.1080\/19490976.2021.1938380","volume":"13","author":"RX Wang","year":"2021","unstructured":"Wang RX, Henen MA, Lee JS, Vogeli B, Colgan SP. Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. Gut Microbes. 2021;13(1):1938380. https:\/\/doi.org\/10.1080\/19490976.2021.1938380.","journal-title":"Gut Microbes"},{"key":"2431_CR42","doi-asserted-by":"publisher","unstructured":"Crowe AR, Yue W. Semi-quantitative determination of protein expression using immunohistochemistry staining and analysis: an integrated protocol. Bio Protoc. 2019;9(24). https:\/\/doi.org\/10.21769\/BioProtoc.3465.","DOI":"10.21769\/BioProtoc.3465"},{"key":"2431_CR43","doi-asserted-by":"publisher","unstructured":"Crowe AR, Yue W. Updated: Semi-quantitative determination of protein expression using immunohistochemistry staining and analysis. Bio Protoc. 2023;2(13). https:\/\/doi.org\/10.21769\/BioProtoc.4610.","DOI":"10.21769\/BioProtoc.4610"},{"issue":"1","key":"2431_CR44","doi-asserted-by":"publisher","first-page":"2490211","DOI":"10.1080\/19490976.2025.2490211","volume":"17","author":"JS Lee","year":"2025","unstructured":"Lee JS, Kao DJ, Worledge CS, Villamaria ZF, Wang RX, Welch NM, et al. E. coli genetically modified for purine nucleobase release promotes butyrate generation and colonic wound healing during DSS insult. Gut Microbes. 2025;17(1):2490211. https:\/\/doi.org\/10.1080\/19490976.2025.2490211.","journal-title":"Gut Microbes"},{"issue":"3","key":"2431_CR45","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1002\/path.1711740312","volume":"174","author":"A Bankfalvi","year":"1994","unstructured":"Bankfalvi A, Navabi H, Bier B, Bocker W, Jasani B, Schmid KW. Wet autoclave pretreatment for antigen retrieval in diagnostic immunohistochemistry. J Pathol. 1994;174(3):223\u20138. https:\/\/doi.org\/10.1002\/path.1711740312.","journal-title":"J Pathol"},{"issue":"22","key":"2431_CR46","doi-asserted-by":"publisher","first-page":"3687","DOI":"10.1007\/s00018-011-0841-0","volume":"68","author":"CV Srikanth","year":"2011","unstructured":"Srikanth CV, Mercado-Lubo R, Hallstrom K, McCormick BA. Salmonella effector proteins and host-cell responses. Cell Mol Life Sci. 2011;68(22):3687\u201397. https:\/\/doi.org\/10.1007\/s00018-011-0841-0.","journal-title":"Cell Mol Life Sci"},{"issue":"4","key":"2431_CR47","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1111\/j.1365-2958.1994.tb00450.x","volume":"13","author":"K Kaniga","year":"1994","unstructured":"Kaniga K, Bossio JC, Galan JE. The Salmonella typhimurium invasion genes invF and invG encode homologues of the AraC and PulD family of proteins. Mol Microbiol. 1994;13(4):555\u201368. https:\/\/doi.org\/10.1111\/j.1365-2958.1994.tb00450.x.","journal-title":"Mol Microbiol"},{"key":"2431_CR48","doi-asserted-by":"publisher","unstructured":"Galan JE, Ginocchio C, Costeas P. Molecular and functional characterization of the Salmonella invasion gene invA: homology of InvA to members of a new protein family. J Bacteriol. 1992;174(13):4338-49. https:\/\/doi.org\/10.1128\/jb.174.13.4338-4349.1992.","DOI":"10.1128\/jb.174.13.4338-4349.1992"},{"issue":"5","key":"2431_CR49","doi-asserted-by":"publisher","first-page":"2839","DOI":"10.1128\/IAI.71.5.2839-2858.2003","volume":"71","author":"M Barthel","year":"2003","unstructured":"Barthel M, Hapfelmeier S, Quintanilla-Martinez L, Kremer M, Rohde M, Hogardt M, et al. Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host. Infect Immun. 2003;71(5):2839\u201358. https:\/\/doi.org\/10.1128\/IAI.71.5.2839-2858.2003.","journal-title":"Infect Immun"},{"issue":"6","key":"2431_CR50","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1159\/000333307","volume":"29","author":"CA Jacobi","year":"2011","unstructured":"Jacobi CA, Malfertheiner P. Escherichia coli Nissle 1917 (Mutaflor): new insights into an old probiotic bacterium. Dig Dis. 2011;29(6):600\u20137. https:\/\/doi.org\/10.1159\/000333307.","journal-title":"Dig Dis"},{"issue":"1","key":"2431_CR51","doi-asserted-by":"publisher","first-page":"5580","DOI":"10.1038\/s41467-019-13336-6","volume":"10","author":"P Praveschotinunt","year":"2019","unstructured":"Praveschotinunt P, Duraj-Thatte AM, Gelfat I, Bahl F, Chou DB, Joshi NS. Engineered E. coli Nissle 1917 for the delivery of matrix-tethered therapeutic domains to the gut. Nat Commun. 2019;10(1):5580. https:\/\/doi.org\/10.1038\/s41467-019-13336-6.","journal-title":"Nat Commun"},{"issue":"10","key":"2431_CR52","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1038\/s42255-023-00897-6","volume":"5","author":"J Vockley","year":"2023","unstructured":"Vockley J, Sondheimer N, Puurunen M, Diaz GA, Ginevic I, Grange DK, et al. Efficacy and safety of a synthetic biotic for treatment of phenylketonuria: a phase 2 clinical trial. Nat Metab. 2023;5(10):1685\u201390. https:\/\/doi.org\/10.1038\/s42255-023-00897-6.","journal-title":"Nat Metab"},{"issue":"1","key":"2431_CR53","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1038\/s41467-024-44776-4","volume":"15","author":"CR Gurbatri","year":"2024","unstructured":"Gurbatri CR, Radford GA, Vrbanac L, Im J, Thomas EM, Coker C, et al. Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia. Nat Commun. 2024;15(1):646. https:\/\/doi.org\/10.1038\/s41467-024-44776-4.","journal-title":"Nat Commun"},{"issue":"10","key":"2431_CR54","doi-asserted-by":"publisher","first-page":"2570","DOI":"10.1128\/MCB.00166-09","volume":"29","author":"G Bellot","year":"2009","unstructured":"Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, Pouyssegur J, et al. Hypoxia-induced autophagy is mediated through Hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol. 2009;29(10):2570\u201381. https:\/\/doi.org\/10.1128\/MCB.00166-09.","journal-title":"Mol Cell Biol"},{"issue":"24","key":"2431_CR55","first-page":"7075","volume":"60","author":"CC Wykoff","year":"2000","unstructured":"Wykoff CC, Beasley NJ, Watson PH, Turner KJ, Pastorek J, Sibtain A, et al. Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res. 2000;60(24):7075\u201383.","journal-title":"Cancer Res"},{"issue":"9","key":"2431_CR56","doi-asserted-by":"publisher","first-page":"4604","DOI":"10.1128\/MCB.16.9.4604","volume":"16","author":"JA Forsythe","year":"1996","unstructured":"Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, et al. Activation of vascular endothelial growth factor gene transcription by Hypoxia-inducible factor 1. Mol Cell Biol. 1996;16(9):4604\u201313. https:\/\/doi.org\/10.1128\/MCB.16.9.4604.","journal-title":"Mol Cell Biol"},{"issue":"36","key":"2431_CR57","doi-asserted-by":"publisher","first-page":"21021","DOI":"10.1074\/jbc.270.36.21021","volume":"270","author":"JD Firth","year":"1995","unstructured":"Firth JD, Ebert BL, Ratcliffe PJ. Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements. J Biol Chem. 1995;270(36):21021\u20137. https:\/\/doi.org\/10.1074\/jbc.270.36.21021.","journal-title":"J Biol Chem"},{"issue":"38","key":"2431_CR58","doi-asserted-by":"publisher","first-page":"23757","DOI":"10.1016\/S0021-9258(17)31580-6","volume":"269","author":"GL Semenza","year":"1994","unstructured":"Semenza GL, Roth PH, Fang HM, Wang GL. Transcriptional regulation of genes encoding glycolytic enzymes by Hypoxia-inducible factor 1. J Biol Chem. 1994;269(38):23757\u201363.","journal-title":"J Biol Chem"},{"issue":"8","key":"2431_CR59","doi-asserted-by":"publisher","first-page":"2976","DOI":"10.4049\/jimmunol.1700105","volume":"199","author":"L Zheng","year":"2017","unstructured":"Zheng L, Kelly CJ, Battista KD, Schaefer R, Lanis JM, Alexeev EE, et al. Microbial-derived butyrate promotes epithelial barrier function through IL-10 receptor-dependent repression of Claudin-2. J Immunol. 2017;199(8):2976\u201384. https:\/\/doi.org\/10.4049\/jimmunol.1700105.","journal-title":"J Immunol"},{"issue":"3","key":"2431_CR60","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/0005-2728(85)90254-3","volume":"807","author":"DS Perlin","year":"1985","unstructured":"Perlin DS, Latchney LR, Senior AE. Inhibition of Escherichia coli H+-ATPase by venturicidin, oligomycin and ossamycin. Biochim Biophys Acta. 1985;807(3):238\u201344. https:\/\/doi.org\/10.1016\/0005-2728(85)90254-3.","journal-title":"Biochim Biophys Acta"},{"issue":"14","key":"2431_CR61","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.1016\/j.febslet.2013.05.047","volume":"587","author":"VB Borisov","year":"2013","unstructured":"Borisov VB, Forte E, Davletshin A, Mastronicola D, Sarti P, Giuffre A. Cytochrome bd oxidase from Escherichia coli displays high catalase activity: an additional defense against oxidative stress. FEBS Lett. 2013;587(14):2214\u20138. https:\/\/doi.org\/10.1016\/j.febslet.2013.05.047.","journal-title":"FEBS Lett"},{"issue":"2","key":"2431_CR62","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1046\/j.1365-2958.2000.01712.x","volume":"35","author":"J Steuber","year":"2000","unstructured":"Steuber J, Schmid C, Rufibach M, Dimroth P. Na+ translocation by complex I (NADH:quinone oxidoreductase) of Escherichia coli. Mol Microbiol. 2000;35(2):428\u201334. https:\/\/doi.org\/10.1046\/j.1365-2958.2000.01712.x.","journal-title":"Mol Microbiol"},{"issue":"27","key":"2431_CR63","doi-asserted-by":"publisher","first-page":"8173","DOI":"10.1073\/pnas.1509743112","volume":"112","author":"MA Lobritz","year":"2015","unstructured":"Lobritz MA, Belenky P, Porter CB, Gutierrez A, Yang JH, Schwarz EG, et al. Antibiotic efficacy is linked to bacterial cellular respiration. Proc Natl Acad Sci U S A. 2015;112(27):8173\u201380. https:\/\/doi.org\/10.1073\/pnas.1509743112.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"19","key":"2431_CR64","doi-asserted-by":"publisher","first-page":"6529","DOI":"10.1128\/AEM.01178-10","volume":"76","author":"VA Portnoy","year":"2010","unstructured":"Portnoy VA, Scott DA, Lewis NE, Tarasova Y, Osterman AL, Palsson BO. Deletion of genes encoding cytochrome oxidases and quinol monooxygenase blocks the aerobic-anaerobic shift in Escherichia coli K-12 MG1655. Appl Environ Microbiol. 2010;76(19):6529\u201340. https:\/\/doi.org\/10.1128\/AEM.01178-10.","journal-title":"Appl Environ Microbiol"},{"issue":"9","key":"2431_CR65","doi-asserted-by":"publisher","first-page":"8358","DOI":"10.1074\/jbc.M412637200","volume":"280","author":"MA Adams","year":"2005","unstructured":"Adams MA, Jia Z. Structural and biochemical evidence for an enzymatic quinone redox cycle in Escherichia coli: identification of a novel quinol monooxygenase. J Biol Chem. 2005;280(9):8358\u201363. https:\/\/doi.org\/10.1074\/jbc.M412637200.","journal-title":"J Biol Chem"},{"issue":"17","key":"2431_CR66","doi-asserted-by":"publisher","first-page":"5510","DOI":"10.1128\/JB.00562-09","volume":"191","author":"M Bekker","year":"2009","unstructured":"Bekker M, de Vries S, Ter Beek A, Hellingwerf KJ, de Mattos MJ. Respiration of Escherichia coli can be fully uncoupled via the nonelectrogenic terminal cytochrome bd-II oxidase. J Bacteriol. 2009;191(17):5510\u20137. https:\/\/doi.org\/10.1128\/JB.00562-09.","journal-title":"J Bacteriol"},{"key":"2431_CR67","doi-asserted-by":"publisher","first-page":"15557","DOI":"10.1038\/ncomms15557","volume":"8","author":"C Morland","year":"2017","unstructured":"Morland C, Andersson KA, Haugen OP, Hadzic A, Kleppa L, Gille A, et al. Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1. Nat Commun. 2017;8:15557. https:\/\/doi.org\/10.1038\/ncomms15557.","journal-title":"Nat Commun"},{"issue":"8","key":"2431_CR68","doi-asserted-by":"publisher","first-page":"3747","DOI":"10.1167\/iovs.18-23892","volume":"59","author":"J Song","year":"2018","unstructured":"Song J, Lee K, Park SW, Chung H, Jung D, Na YR, et al. Lactic acid upregulates VEGF expression in macrophages and facilitates choroidal neovascularization. Invest Ophthalmol Vis Sci. 2018;59(8):3747\u201354. https:\/\/doi.org\/10.1167\/iovs.18-23892.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"3","key":"2431_CR69","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1111\/j.1743-6109.2006.00127.x","volume":"14","author":"S Beckert","year":"2006","unstructured":"Beckert S, Farrahi F, Aslam RS, Scheuenstuhl H, Konigsrainer A, Hussain MZ, et al. Lactate stimulates endothelial cell migration. Wound Repair Regen. 2006;14(3):321\u20134. https:\/\/doi.org\/10.1111\/j.1743-6109.2006.00127.x.","journal-title":"Wound Repair Regen"},{"issue":"14","key":"2431_CR70","doi-asserted-by":"publisher","first-page":"4587","DOI":"10.1093\/nar\/gkp425","volume":"37","author":"Y Benita","year":"2009","unstructured":"Benita Y, Kikuchi H, Smith AD, Zhang MQ, Chung DC, Xavier RJ. An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia. Nucleic Acids Res. 2009;37(14):4587\u2013602. https:\/\/doi.org\/10.1093\/nar\/gkp425.","journal-title":"Nucleic Acids Res"},{"issue":"1-2","key":"2431_CR71","doi-asserted-by":"publisher","first-page":"e977176","DOI":"10.4161\/21688370.2014.977176","volume":"3","author":"J Luettig","year":"2015","unstructured":"Luettig J, Rosenthal R, Barmeyer C, Schulzke JD. Claudin-2 as a mediator of leaky gut barrier during intestinal inflammation. Tissue Barriers. 2015;3(1\u20132):e977176. https:\/\/doi.org\/10.4161\/21688370.2014.977176.","journal-title":"Tissue Barriers"},{"issue":"4","key":"2431_CR72","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.dld.2024.08.001","volume":"57","author":"V Villanacci","year":"2025","unstructured":"Villanacci V, Del Sordo R, Lanzarotto F, Ricci C, Sidoni A, Manenti S, et al. Claudin-2: a marker for a better evaluation of histological mucosal healing in inflammatory bowel diseases. Dig Liver Dis. 2025;57(4):827\u201332. https:\/\/doi.org\/10.1016\/j.dld.2024.08.001.","journal-title":"Dig Liver Dis"},{"issue":"4","key":"2431_CR73","doi-asserted-by":"publisher","first-page":"C1087","DOI":"10.1152\/ajpcell.00472.2024","volume":"327","author":"T Wang","year":"2024","unstructured":"Wang T, Wang RX, Colgan SP. Physiologic hypoxia in the intestinal mucosa: a central role for short-chain fatty acids. Am J Physiol Cell Physiol. 2024;327(4):C1087\u201393. https:\/\/doi.org\/10.1152\/ajpcell.00472.2024.","journal-title":"Am J Physiol Cell Physiol"},{"issue":"23","key":"2431_CR74","doi-asserted-by":"publisher","first-page":"3830","DOI":"10.1038\/sj.onc.1208531","volume":"24","author":"SM Paltoglou","year":"2005","unstructured":"Paltoglou SM, Roberts BJ. Role of the von Hippel-Lindau tumour suppressor protein in the regulation of HIF-1alpha and its oxygen-regulated transactivation domains at high cell density. Oncogene. 2005;24(23):3830\u20135. https:\/\/doi.org\/10.1038\/sj.onc.1208531.","journal-title":"Oncogene"},{"key":"2431_CR75","doi-asserted-by":"publisher","unstructured":"Strowitzki MJ, Cummins EP, Taylor CT. Protein Hydroxylation by Hypoxia-Inducible Factor (HIF) Hydroxylases: Unique or Ubiquitous? Cells. 2019;8(5). https:\/\/doi.org\/10.3390\/cells8050384.","DOI":"10.3390\/cells8050384"},{"issue":"1","key":"2431_CR76","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1096\/fj.14-259663","volume":"29","author":"VF Curtis","year":"2015","unstructured":"Curtis VF, Ehrentraut SF, Campbell EL, Glover LE, Bayless A, Kelly CJ, et al. Stabilization of HIF through inhibition of Cullin-2 neddylation is protective in mucosal inflammatory responses. FASEB J. 2015;29(1):208\u201315. https:\/\/doi.org\/10.1096\/fj.14-259663.","journal-title":"FASEB J"},{"key":"2431_CR77","doi-asserted-by":"publisher","unstructured":"Albanese A, Daly LA, Mennerich D, Kietzmann T, See V. The role of hypoxia-inducible factor post-translational modifications in regulating its localisation, stability, and activity. Int J Mol Sci. 2020;22(1). https:\/\/doi.org\/10.3390\/ijms22010268.","DOI":"10.3390\/ijms22010268"},{"issue":"3","key":"2431_CR78","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.cell.2007.08.045","volume":"131","author":"J Cheng","year":"2007","unstructured":"Cheng J, Kang X, Zhang S, Yeh ET. SUMO-specific protease 1 is essential for stabilization of HIF1alpha during hypoxia. Cell. 2007;131(3):584\u201395. https:\/\/doi.org\/10.1016\/j.cell.2007.08.045.","journal-title":"Cell"},{"issue":"39","key":"2431_CR79","doi-asserted-by":"publisher","first-page":"20661","DOI":"10.1074\/jbc.M116.749291","volume":"291","author":"MC Chan","year":"2016","unstructured":"Chan MC, Ilott NE, Schodel J, Sims D, Tumber A, Lippl K, et al. Tuning the transcriptional response to hypoxia by inhibiting hypoxia-inducible factor (HIF) prolyl and asparaginyl hydroxylases. J Biol Chem. 2016;291(39):20661\u201373. https:\/\/doi.org\/10.1074\/jbc.M116.749291.","journal-title":"J Biol Chem"},{"issue":"5","key":"2431_CR80","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/nri3430","volume":"13","author":"N Kamada","year":"2013","unstructured":"Kamada N, Seo SU, Chen GY, Nunez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol. 2013;13(5):321\u201335. https:\/\/doi.org\/10.1038\/nri3430.","journal-title":"Nat Rev Immunol"},{"issue":"7","key":"2431_CR81","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/s41577-019-0268-7","volume":"20","author":"R Caruso","year":"2020","unstructured":"Caruso R, Lo BC, Nunez G. Host-microbiota interactions in inflammatory bowel disease. Nat Rev Immunol. 2020;20(7):411\u201326. https:\/\/doi.org\/10.1038\/s41577-019-0268-7.","journal-title":"Nat Rev Immunol"},{"issue":"2 Pt A","key":"2431_CR82","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.imlet.2014.04.014","volume":"162","author":"F Faber","year":"2014","unstructured":"Faber F, Baumler AJ. The impact of intestinal inflammation on the nutritional environment of the gut microbiota. Immunol Lett. 2014;162(2 Pt A):48\u201353. https:\/\/doi.org\/10.1016\/j.imlet.2014.04.014.","journal-title":"Immunol Lett"},{"issue":"6351","key":"2431_CR83","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1126\/science.aao2202","volume":"357","author":"PD Cani","year":"2017","unstructured":"Cani PD. Gut cell metabolism shapes the microbiome. Science. 2017;357(6351):548\u20139. https:\/\/doi.org\/10.1126\/science.aao2202.","journal-title":"Science"},{"issue":"16","key":"2431_CR84","doi-asserted-by":"publisher","first-page":"6039","DOI":"10.1074\/jbc.RA117.000269","volume":"293","author":"JS Lee","year":"2018","unstructured":"Lee JS, Wang RX, Alexeev EE, Lanis JM, Battista KD, Glover LE, et al. Hypoxanthine is a checkpoint stress metabolite in colonic epithelial energy modulation and barrier function. J Biol Chem. 2018;293(16):6039\u201351. https:\/\/doi.org\/10.1074\/jbc.RA117.000269.","journal-title":"J Biol Chem"},{"issue":"Supplement_3","key":"2431_CR85","doi-asserted-by":"publisher","first-page":"S233","DOI":"10.1513\/AnnalsATS.201608-610MG","volume":"14","author":"LE Glover","year":"2017","unstructured":"Glover LE, Colgan SP. Epithelial barrier regulation by hypoxia-inducible factor. Ann Am Thorac Soc. 2017;14(Supplement_3):S233\u20136. https:\/\/doi.org\/10.1513\/AnnalsATS.201608-610MG.","journal-title":"Ann Am Thorac Soc"},{"issue":"1","key":"2431_CR86","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.chom.2018.12.003","volume":"25","author":"Y Litvak","year":"2019","unstructured":"Litvak Y, Mon KKZ, Nguyen H, Chanthavixay G, Liou M, Velazquez EM, et al. Commensal enterobacteriaceae protect against Salmonella colonization through oxygen competition. Cell Host Microbe. 2019;25(1):128-39 e5. https:\/\/doi.org\/10.1016\/j.chom.2018.12.003.","journal-title":"Cell Host Microbe"},{"issue":"7","key":"2431_CR87","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1016\/j.chom.2024.05.008","volume":"32","author":"HP Savage","year":"2024","unstructured":"Savage HP, Bays DJ, Tiffany CR, Gonzalez MAF, Bejarano EJ, Carvalho TP, et al. Epithelial hypoxia maintains colonization resistance against Candida albicans. Cell Host Microbe. 2024;32(7):1103-13 e6. https:\/\/doi.org\/10.1016\/j.chom.2024.05.008.","journal-title":"Cell Host Microbe"},{"issue":"6","key":"2431_CR88","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/j.chom.2020.09.005","volume":"28","author":"RB Chanin","year":"2020","unstructured":"Chanin RB, Winter MG, Spiga L, Hughes ER, Zhu W, Taylor SJ, et al. Epithelial-derived reactive oxygen species enable AppBCX-mediated aerobic respiration of Escherichia coli during intestinal inflammation. Cell Host Microbe. 2020;28(6):780-8 e5. https:\/\/doi.org\/10.1016\/j.chom.2020.09.005.","journal-title":"Cell Host Microbe"},{"key":"2431_CR89","doi-asserted-by":"publisher","unstructured":"Lopez CA, Winter SE, Rivera-Chavez F, Xavier MN, Poon V, Nuccio SP, et al. Phage-mediated acquisition of a type III secreted effector protein boosts growth of salmonella by nitrate respiration. mBio. 2012;3(3). https:\/\/doi.org\/10.1128\/mBio.00143-12.","DOI":"10.1128\/mBio.00143-12"},{"issue":"9","key":"2431_CR90","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.tibtech.2015.06.011","volume":"33","author":"NR Shin","year":"2015","unstructured":"Shin NR, Whon TW, Bae JW. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol. 2015;33(9):496\u2013503. https:\/\/doi.org\/10.1016\/j.tibtech.2015.06.011.","journal-title":"Trends Biotechnol"},{"issue":"7415","key":"2431_CR91","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/nature11550","volume":"489","author":"CA Lozupone","year":"2012","unstructured":"Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220\u201330. https:\/\/doi.org\/10.1038\/nature11550.","journal-title":"Nature"},{"issue":"3","key":"2431_CR92","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1111\/mmi.15296","volume":"122","author":"R Melki","year":"2024","unstructured":"Melki R, Litvak Y. From vacant to vivid: the nutritional landscape drives infant gut microbiota establishment. Mol Microbiol. 2024;122(3):347\u201356. https:\/\/doi.org\/10.1111\/mmi.15296.","journal-title":"Mol Microbiol"},{"issue":"1","key":"2431_CR93","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.immuni.2013.11.020","volume":"40","author":"EL Campbell","year":"2014","unstructured":"Campbell EL, Bruyninckx WJ, Kelly CJ, Glover LE, McNamee EN, Bowers BE, et al. Transmigrating neutrophils shape the mucosal microenvironment through localized oxygen depletion to influence resolution of inflammation. Immunity. 2014;40(1):66\u201377. https:\/\/doi.org\/10.1016\/j.immuni.2013.11.020.","journal-title":"Immunity"},{"issue":"2","key":"2431_CR94","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1097\/JIM.0000000000000218","volume":"64","author":"SP Colgan","year":"2016","unstructured":"Colgan SP. Targeting hypoxia in inflammatory bowel disease. J Investig Med. 2016;64(2):364\u20138. https:\/\/doi.org\/10.1097\/JIM.0000000000000218.","journal-title":"J Investig Med"},{"issue":"5","key":"2431_CR95","doi-asserted-by":"publisher","first-page":"949","DOI":"10.3904\/kjim.2021.458","volume":"37","author":"SK Park","year":"2022","unstructured":"Park SK, Kang SB, Kim S, Kim TO, Cha JM, Im JP, et al. Additive effect of probiotics (Mutaflor) on 5-aminosalicylic acid therapy in patients with ulcerative colitis. Korean J Intern Med. 2022;37(5):949\u201357. https:\/\/doi.org\/10.3904\/kjim.2021.458.","journal-title":"Korean J Intern Med"},{"issue":"9","key":"2431_CR96","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1038\/s42255-022-00635-4","volume":"4","author":"MK Puurunen","year":"2022","unstructured":"Puurunen MK, Vockley J, Searle SL, Sacharow SJ, Phillips JA 3rd, Denney WS, et al. Publisher Correction: safety and pharmacodynamics of an engineered E. coli Nissle for the treatment of phenylketonuria: a first-in-human phase 1\/2a study. Nat Metab. 2022;4(9):1214. https:\/\/doi.org\/10.1038\/s42255-022-00635-4.","journal-title":"Nat Metab"},{"key":"2431_CR97","doi-asserted-by":"publisher","unstructured":"Cartwright IM, Dowdell AS, Lanis JM, Brink KR, Mu A, Kostelecky RE, et al. Mucosal acidosis elicits a unique molecular signature in epithelia and intestinal tissue mediated by GPR31-induced CREB phosphorylation. Proc Natl Acad Sci U S A. 2021;118(20). https:\/\/doi.org\/10.1073\/pnas.2023871118.","DOI":"10.1073\/pnas.2023871118"},{"issue":"32","key":"2431_CR98","doi-asserted-by":"publisher","first-page":"e2221121120","DOI":"10.1073\/pnas.2221121120","volume":"120","author":"JY Xia","year":"2023","unstructured":"Xia JY, Hepler C, Tran P, Waldeck NJ, Bass J, Prindle A. Engineered calprotectin-sensing probiotics for IBD surveillance in humans. Proc Natl Acad Sci U S A. 2023;120(32):e2221121120. https:\/\/doi.org\/10.1073\/pnas.2221121120.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2431_CR99","doi-asserted-by":"publisher","first-page":"1124774","DOI":"10.3389\/fimmu.2023.1124774","volume":"14","author":"IM Cartwright","year":"2023","unstructured":"Cartwright IM, Colgan SP. The hypoxic tissue microenvironment as a driver of mucosal inflammatory resolution. Front Immunol. 2023;14:1124774. https:\/\/doi.org\/10.3389\/fimmu.2023.1124774.","journal-title":"Front Immunol"}],"container-title":["Microbiome"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40168-026-02431-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40168-026-02431-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40168-026-02431-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:48:32Z","timestamp":1785455312000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40168-026-02431-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,30]]},"references-count":99,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2431"],"URL":"https:\/\/doi.org\/10.1186\/s40168-026-02431-8","relation":{},"ISSN":["2049-2618"],"issn-type":[{"value":"2049-2618","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,30]]},"assertion":[{"value":"11 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"No human subjects were involved in these studies. Animal procedures were conducted under an approved IACUC protocol (#00182) in an AAALAC-accredited (#00235) and USDA-inspected (#84-R-0059) facility.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"191"}}