{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:05:11Z","timestamp":1770905111337,"version":"3.50.1"},"reference-count":83,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":31,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000057","name":"U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["5R35GM143009"],"award-info":[{"award-number":["5R35GM143009"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-025-09504-8","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T10:15:34Z","timestamp":1768212934000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ZIP8 loss impairs macrophage-mediated phagolysosomal removal of bacteria and is overcome by butyrate supplementation"],"prefix":"10.1038","volume":"9","author":[{"given":"Deandra R.","family":"Smith","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabah","family":"Haq","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Niu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunayana","family":"Malla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2974-0243","authenticated-orcid":false,"given":"Rajib","family":"Saha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3661-2496","authenticated-orcid":false,"given":"Ashley","family":"Peer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piero","family":"Bianco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Romanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5356-1413","authenticated-orcid":false,"given":"Derrick R.","family":"Samuelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9977-2857","authenticated-orcid":false,"given":"Daren L.","family":"Knoell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"9504_CR1","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1086\/657313","volume":"51","author":"TM File Jr.","year":"2010","unstructured":"File, T. M. Jr. et al. Integrated analysis of FOCUS 1 and FOCUS 2: randomized, doubled-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with community-acquired pneumonia. Clin. Infect. Dis. 51, 1395\u20131405 (2010).","journal-title":"Clin. Infect. Dis."},{"key":"9504_CR2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.jinf.2013.03.003","volume":"67","author":"DM Musher","year":"2013","unstructured":"Musher, D. M. et al. Can an etiologic agent be identified in adults who are hospitalized for community-acquired pneumonia: results of a one-year study. J. Infect. 67, 11\u201318 (2013).","journal-title":"J. Infect."},{"key":"9504_CR3","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1378\/chest.07-1456","volume":"133","author":"MI Restrepo","year":"2008","unstructured":"Restrepo, M. I., Mortensen, E. M., Velez, J. A., Frei, C. & Anzueto, A. A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU. Chest 133, 610\u2013617 (2008).","journal-title":"Chest"},{"key":"9504_CR4","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1093\/infdis\/jit506","volume":"208","author":"RL Sherwin","year":"2013","unstructured":"Sherwin, R. L. et al. Distribution of 13-valent pneumococcal conjugate vaccine Streptococcus pneumoniae serotypes in US adults aged >\/=50 years with community-acquired pneumonia. J. Infect. Dis. 208, 1813\u20131820 (2013).","journal-title":"J. Infect. Dis."},{"key":"9504_CR5","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1007\/s10522-015-9614-8","volume":"17","author":"MT Goncalves","year":"2016","unstructured":"Goncalves, M. T., Mitchell, T. J. & Lord, J. M. Immune ageing and susceptibility to Streptococcus pneumoniae. Biogerontology 17, 449\u2013465 (2016).","journal-title":"Biogerontology"},{"key":"9504_CR6","doi-asserted-by":"publisher","first-page":"1407S","DOI":"10.1093\/jn\/130.5.1407S","volume":"130","author":"L Rink","year":"2000","unstructured":"Rink, L. & Kirchner, H. Zinc-altered immune function and cytokine production. J. Nutr. 130, 1407S\u20131411S (2000).","journal-title":"J. Nutr."},{"key":"9504_CR7","doi-asserted-by":"publisher","first-page":"1399S","DOI":"10.1093\/jn\/130.5.1399S","volume":"130","author":"PJ Fraker","year":"2000","unstructured":"Fraker, P. J., King, L. E., Laakko, T. & Vollmer, T. L. The dynamic link between the integrity of the immune system and zinc status. J. Nutr. 130, 1399S\u20131406S (2000).","journal-title":"J. Nutr."},{"key":"9504_CR8","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1146\/annurev.nutr.24.012003.132454","volume":"24","author":"PJ Fraker","year":"2004","unstructured":"Fraker, P. J. & King, L. E. Reprogramming of the immune system during zinc deficiency. Annu Rev. Nutr. 24, 277\u2013298 (2004).","journal-title":"Annu Rev. Nutr."},{"key":"9504_CR9","unstructured":"Maxfield, L., Shukla, S., and Crane, J. S. Zinc Deficiency (In StatPearls, 2024)."},{"key":"9504_CR10","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1146\/annurev.nutr.23.011702.073054","volume":"24","author":"C Fischer Walker","year":"2004","unstructured":"Fischer Walker, C. & Black, R. E. Zinc and the risk for infectious disease. Annu Rev. Nutr. 24, 255\u2013275 (2004).","journal-title":"Annu Rev. Nutr."},{"key":"9504_CR11","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/S0047-6374(00)00194-9","volume":"121","author":"E Mocchegiani","year":"2000","unstructured":"Mocchegiani, E., Giacconi, R., Muzzioli, M. & Cipriano, C. Zinc, infections and immunosenescence. Mech. Ageing Dev. 121, 21\u201335 (2000).","journal-title":"Mech. Ageing Dev."},{"key":"9504_CR12","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1111\/j.1753-4887.2009.00253.x","volume":"68","author":"JB Barnett","year":"2010","unstructured":"Barnett, J. B., Hamer, D. H. & Meydani, S. N. Low zinc status: A new risk factor for pneumonia in the elderly?. Nutr. Rev. 68, 30\u201337 (2010).","journal-title":"Nutr. Rev."},{"key":"9504_CR13","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1146\/annurev-nutr-033009-083312","volume":"29","author":"LA Lichten","year":"2009","unstructured":"Lichten, L. A. & Cousins, R. J. Mammalian zinc transporters: nutritional and physiologic regulation. Annu Rev. Nutr. 29, 153\u2013176 (2009).","journal-title":"Annu Rev. Nutr."},{"key":"9504_CR14","doi-asserted-by":"publisher","first-page":"17029","DOI":"10.1038\/sigtrans.2017.29","volume":"2","author":"E Bafaro","year":"2017","unstructured":"Bafaro, E., Liu, Y., Xu, Y. & Dempski, R. E. The emerging role of zinc transporters in cellular homeostasis and cancer. Signal Transduct. Target Ther. 2, 17029 (2017).","journal-title":"Signal Transduct. Target Ther."},{"key":"9504_CR15","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.abb.2016.06.020","volume":"611","author":"S Hojyo","year":"2016","unstructured":"Hojyo, S. & Fukada, T. Zinc transporters and signaling in physiology and pathogenesis. Arch. Biochem. Biophys. 611, 43\u201350 (2016).","journal-title":"Arch. Biochem. Biophys."},{"key":"9504_CR16","doi-asserted-by":"publisher","first-page":"924820","DOI":"10.3389\/fcell.2022.924820","volume":"10","author":"DR Samuelson","year":"2022","unstructured":"Samuelson, D. R., Haq, S. & Knoell, D. L. Divalent metal uptake and the role of ZIP8 in host defense against pathogens. Front Cell Dev. Biol. 10, 924820 (2022).","journal-title":"Front Cell Dev. Biol."},{"key":"9504_CR17","doi-asserted-by":"publisher","first-page":"e0169531","DOI":"10.1371\/journal.pone.0169531","volume":"12","author":"CJ Pyle","year":"2017","unstructured":"Pyle, C. J. et al. Zinc modulates endotoxin-induced human macrophage inflammation through ZIP8 induction and C\/EBPbeta Inhibition. PLoS One 12, e0169531 (2017).","journal-title":"PLoS One"},{"key":"9504_CR18","doi-asserted-by":"publisher","first-page":"L1127","DOI":"10.1152\/ajplung.00057.2008","volume":"294","author":"B Besecker","year":"2008","unstructured":"Besecker, B. et al. The human zinc transporter SLC39A8 (Zip8) is critical in zinc-mediated cytoprotection in lung epithelia. Am. J. Physiol. Lung Cell Mol. Physiol. 294, L1127\u2013L1136 (2008).","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"9504_CR19","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.celrep.2013.01.009","volume":"3","author":"MJ Liu","year":"2013","unstructured":"Liu, M. J. et al. ZIP8 regulates host defense through zinc-mediated inhibition of NF-kappaB. Cell Rep. 3, 386\u2013400 (2013).","journal-title":"Cell Rep."},{"key":"9504_CR20","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1002\/ajmg.b.32545","volume":"177","author":"J Costas","year":"2018","unstructured":"Costas, J. The highly pleiotropic gene SLC39A8 as an opportunity to gain insight into the molecular pathogenesis of schizophrenia. Am. J. Med. Genet. B Neuropsychiatr. Genet. 177, 274\u2013283 (2018).","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"9504_CR21","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/ng.3570","volume":"48","author":"JK Pickrell","year":"2016","unstructured":"Pickrell, J. K. et al. Detection and interpretation of shared genetic influences on 42 human traits. Nat. Genet. 48, 709\u2013717 (2016).","journal-title":"Nat. Genet."},{"key":"9504_CR22","doi-asserted-by":"publisher","first-page":"125","DOI":"10.3389\/fgene.2014.00125","volume":"5","author":"Z Ye","year":"2014","unstructured":"Ye, Z. et al. Genome wide association study of SNP-, gene-, and pathway-based approaches to identify genes influencing susceptibility to Staphylococcus aureus infections. Front. Genet. 5, 125 (2014).","journal-title":"Front. Genet."},{"key":"9504_CR23","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.4049\/jimmunol.2001395","volume":"207","author":"SC Hall","year":"2021","unstructured":"Hall, S. C. et al. Critical role of zinc transporter (ZIP8) in myeloid innate immune cell function and the host response against bacterial pneumonia. J. Immunol. 207, 1357\u20131370 (2021).","journal-title":"J. Immunol."},{"key":"9504_CR24","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1097\/CCM.0b013e31819cefe4","volume":"37","author":"DL Knoell","year":"2009","unstructured":"Knoell, D. L. et al. Zinc deficiency increases organ damage and mortality in a murine model of polymicrobial sepsis. Crit. Care Med. 37, 1380\u20131388 (2009).","journal-title":"Crit. Care Med."},{"key":"9504_CR25","doi-asserted-by":"publisher","first-page":"601072","DOI":"10.3389\/fcimb.2020.601072","volume":"10","author":"L Szulc-Dabrowska","year":"2020","unstructured":"Szulc-Dabrowska, L., Bossowska-Nowicka, M., Struzik, J. & Toka, F. N. Cathepsins in bacteria-macrophage interaction: Defenders or victims of circumstance?. Front. Cell Infect. Microbiol 10, 601072 (2020).","journal-title":"Front. Cell Infect. Microbiol"},{"key":"9504_CR26","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1042\/BCJ20160780","volume":"474","author":"B Carroll","year":"2017","unstructured":"Carroll, B. & Dunlop, E. A. The lysosome: a crucial hub for AMPK and mTORC1 signalling. Biochem. J. 474, 1453\u20131466 (2017).","journal-title":"Biochem. J."},{"key":"9504_CR27","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1083\/jcb.201607005","volume":"214","author":"CY Lim","year":"2016","unstructured":"Lim, C. Y. & Zoncu, R. The lysosome as a command-and-control center for cellular metabolism. J. Cell Biol. 214, 653\u2013664 (2016).","journal-title":"J. Cell Biol."},{"key":"9504_CR28","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1126\/science.1174447","volume":"325","author":"M Sardiello","year":"2009","unstructured":"Sardiello, M. et al. A gene network regulating lysosomal biogenesis and function. Science 325, 473\u2013477 (2009).","journal-title":"Science"},{"key":"9504_CR29","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.cmet.2014.06.014","volume":"20","author":"CS Zhang","year":"2014","unstructured":"Zhang, C. S. et al. The lysosomal v-ATPase-ragulator complex is a common activator for AMPK and mTORC1, acting as a switch between catabolism and anabolism. Cell Metab. 20, 526\u2013540 (2014).","journal-title":"Cell Metab."},{"key":"9504_CR30","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1016\/j.cub.2016.05.070","volume":"26","author":"MA Gray","year":"2016","unstructured":"Gray, M. A. et al. Phagocytosis enhances lysosomal and bactericidal properties by activating the transcription factor TFEB. Curr. Biol. 26, 1955\u20131964 (2016).","journal-title":"Curr. Biol."},{"key":"9504_CR31","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1080\/15548627.2016.1179405","volume":"12","author":"N Pastore","year":"2016","unstructured":"Pastore, N. et al. TFEB and TFE3 cooperate in the regulation of the innate immune response in activated macrophages. Autophagy 12, 1240\u20131258 (2016).","journal-title":"Autophagy"},{"key":"9504_CR32","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/j.immuni.2014.05.002","volume":"40","author":"O Visvikis","year":"2014","unstructured":"Visvikis, O. et al. Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes. Immunity 40, 896\u2013909 (2014).","journal-title":"Immunity"},{"key":"9504_CR33","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12824","author":"VEB Hipolito","year":"2018","unstructured":"Hipolito, V. E. B., Ospina-Escobar, E. & Botelho, R. J. Lysosome remodelling and adaptation during phagocyte activation. Cell Microbiol. https:\/\/doi.org\/10.1111\/cmi.12824 (2018).","journal-title":"Cell Microbiol."},{"key":"9504_CR34","first-page":"1043","volume":"14","author":"J Zhang","year":"2018","unstructured":"Zhang, J. et al. Importance of TFEB acetylation in control of its transcriptional activity and lysosomal function in response to histone deacetylase inhibitors. Autophagy 14, 1043\u20131059 (2018).","journal-title":"Autophagy"},{"key":"9504_CR35","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens12050639","author":"DR Samuelson","year":"2023","unstructured":"Samuelson, D. R. et al. The inherited intestinal microbiota from myeloid-specific ZIP8KO mice impairs pulmonary host defense against pneumococcal pneumonia. Pathogens https:\/\/doi.org\/10.3390\/pathogens12050639 (2023).","journal-title":"Pathogens"},{"key":"9504_CR36","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.immuni.2018.12.018","volume":"50","author":"J Schulthess","year":"2019","unstructured":"Schulthess, J. et al. The short chain fatty acid butyrate imprints an antimicrobial program in macrophages. Immunity 50, 432\u2013445 e437 (2019).","journal-title":"Immunity"},{"key":"9504_CR37","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031022","author":"DR Samuelson","year":"2022","unstructured":"Samuelson, D. R. et al. ZIP8-mediated intestinal dysbiosis impairs pulmonary host defense against bacterial pneumonia. Int J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms23031022 (2022).","journal-title":"Int J. Mol. Sci."},{"key":"9504_CR38","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/nbt.1614","volume":"28","author":"JD Orth","year":"2010","unstructured":"Orth, J. D., Thiele, I. & Palsson, B. O. What is flux balance analysis?. Nat. Biotechnol. 28, 245\u2013248 (2010).","journal-title":"Nat. Biotechnol."},{"key":"9504_CR39","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-489","volume":"11","author":"S Gudmundsson","year":"2010","unstructured":"Gudmundsson, S. & Thiele, I. Computationally efficient flux variability analysis. BMC Bioinforma. 11, 489 (2010).","journal-title":"BMC Bioinforma."},{"key":"9504_CR40","doi-asserted-by":"publisher","first-page":"13638","DOI":"10.1073\/pnas.0703262104","volume":"104","author":"PJ Kim","year":"2007","unstructured":"Kim, P. J. et al. Metabolite essentiality elucidates robustness of Escherichia coli metabolism. Proc. Natl. Acad. Sci. USA 104, 13638\u201313642 (2007).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"9504_CR41","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1471-2466-7-13","volume":"7","author":"DD Sin","year":"2007","unstructured":"Sin, D. D., Leung, R., Gan, W. Q. & Man, S. P. Circulating surfactant protein D as a potential lung-specific biomarker of health outcomes in COPD: a pilot study. BMC Pulm. Med. 7, 13 (2007).","journal-title":"BMC Pulm. Med."},{"key":"9504_CR42","doi-asserted-by":"publisher","first-page":"e0001522","DOI":"10.1128\/cmr.00015-22","volume":"35","author":"NJ Gadsby","year":"2022","unstructured":"Gadsby, N. J. & Musher, D. M. The microbial etiology of community-acquired pneumonia in adults: from classical bacteriology to host transcriptional signatures. Clin. Microbiol Rev. 35, e0001522 (2022).","journal-title":"Clin. Microbiol Rev."},{"key":"9504_CR43","doi-asserted-by":"publisher","first-page":"S14","DOI":"10.1017\/S0007114508006818","volume":"99","author":"RS Gibson","year":"2008","unstructured":"Gibson, R. S., Hess, S. Y., Hotz, C. & Brown, K. H. Indicators of zinc status at the population level: a review of the evidence. Br. J. Nutr. 99, S14\u2013S23 (2008).","journal-title":"Br. J. Nutr."},{"key":"9504_CR44","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1093\/ajcn\/85.3.837","volume":"85","author":"AS Prasad","year":"2007","unstructured":"Prasad, A. S. et al. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am. J. Clin. Nutr. 85, 837\u2013844 (2007).","journal-title":"Am. J. Clin. Nutr."},{"key":"9504_CR45","doi-asserted-by":"publisher","first-page":"e1007957","DOI":"10.1371\/journal.ppat.1007957","volume":"15","author":"BA Eijkelkamp","year":"2019","unstructured":"Eijkelkamp, B. A. et al. Dietary zinc and the control of Streptococcus pneumoniae infection. PLoS Pathog. 15, e1007957 (2019).","journal-title":"PLoS Pathog."},{"key":"9504_CR46","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20130014","author":"SL Stafford","year":"2013","unstructured":"Stafford, S. L. et al. Metal ions in macrophage antimicrobial pathways: emerging roles for zinc and copper. Biosci. Rep. https:\/\/doi.org\/10.1042\/BSR20130014 (2013).","journal-title":"Biosci. Rep."},{"key":"9504_CR47","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1086\/656191","volume":"202","author":"MS Winters","year":"2010","unstructured":"Winters, M. S., Chan, Q., Caruso, J. A. & Deepe, G. S. Jr Metallomic analysis of macrophages infected with Histoplasma capsulatum reveals a fundamental role for zinc in host defenses. J. Infect. Dis. 202, 1136\u20131145 (2010).","journal-title":"J. Infect. Dis."},{"key":"9504_CR48","doi-asserted-by":"publisher","DOI":"10.13172\/2053-0285-1-2-861","author":"AJ Mehta","year":"2013","unstructured":"Mehta, A. J. Pulmonary consequences of alcoholism: a critical review. OA Alcohol https:\/\/doi.org\/10.13172\/2053-0285-1-2-861 (2013).","journal-title":"OA Alcohol"},{"key":"9504_CR49","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1164\/rccm.201301-0061OC","volume":"188","author":"AJ Mehta","year":"2013","unstructured":"Mehta, A. J., Yeligar, S. M., Elon, L., Brown, L. A. & Guidot, D. M. Alcoholism causes alveolar macrophage zinc deficiency and immune dysfunction. Am. J. Respir. Crit. Care Med. 188, 716\u2013723 (2013).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"9504_CR50","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.3945\/jn.109.111492","volume":"140","author":"A Sheikh","year":"2010","unstructured":"Sheikh, A. et al. Zinc influences innate immune responses in children with enterotoxigenic Escherichia coli-induced diarrhea. J. Nutr. 140, 1049\u20131056 (2010).","journal-title":"J. Nutr."},{"key":"9504_CR51","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1016\/j.ajhg.2015.11.003","volume":"97","author":"JH Park","year":"2015","unstructured":"Park, J. H. et al. SLC39A8 deficiency: a disorder of manganese transport and glycosylation. Am. J. Hum. Genet. 97, 894\u2013903 (2015).","journal-title":"Am. J. Hum. Genet."},{"key":"9504_CR52","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1016\/j.ajhg.2015.11.002","volume":"97","author":"KM Boycott","year":"2015","unstructured":"Boycott, K. M. et al. Autosomal-recessive intellectual disability with cerebellar atrophy syndrome caused by mutation of the manganese and zinc transporter gene SLC39A8. Am. J. Hum. Genet. 97, 886\u2013893 (2015).","journal-title":"Am. J. Hum. Genet."},{"key":"9504_CR53","doi-asserted-by":"publisher","first-page":"34032","DOI":"10.1074\/jbc.M112.367284","volume":"287","author":"CY Wang","year":"2012","unstructured":"Wang, C. Y. et al. ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. J. Biol. Chem. 287, 34032\u201334043 (2012).","journal-title":"J. Biol. Chem."},{"key":"9504_CR54","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1084\/jem.20151938","volume":"213","author":"X Qi","year":"2016","unstructured":"Qi, X. et al. Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection. J. Exp. Med. 213, 2081\u20132097 (2016).","journal-title":"J. Exp. Med."},{"key":"9504_CR55","doi-asserted-by":"publisher","first-page":"903","DOI":"10.4161\/auto.19653","volume":"8","author":"JA Martina","year":"2012","unstructured":"Martina, J. A., Chen, Y., Gucek, M. & Puertollano, R. MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. Autophagy 8, 903\u2013914 (2012).","journal-title":"Autophagy"},{"key":"9504_CR56","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1038\/emboj.2012.32","volume":"31","author":"C Settembre","year":"2012","unstructured":"Settembre, C. et al. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 31, 1095\u20131108 (2012).","journal-title":"EMBO J."},{"key":"9504_CR57","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/s41420-024-01850-6","volume":"10","author":"H Chen","year":"2024","unstructured":"Chen, H. et al. From the regulatory mechanism of TFEB to its therapeutic implications. Cell Death Discov. 10, 84 (2024).","journal-title":"Cell Death Discov."},{"key":"9504_CR58","doi-asserted-by":"publisher","first-page":"R323","DOI":"10.1152\/ajpregu.00444.2017","volume":"315","author":"OC Rivera","year":"2018","unstructured":"Rivera, O. C., Hennigar, S. R. & Kelleher, S. L. ZnT2 is critical for lysosome acidification and biogenesis during mammary gland involution. Am. J. Physiol. Regul. Integr. Comp. Physiol. 315, R323\u2013R335 (2018).","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"9504_CR59","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1002\/glia.23952","volume":"69","author":"H Lee","year":"2021","unstructured":"Lee, H. & Koh, J. Y. Roles for H(+) \/K(+) -ATPase and zinc transporter 3 in cAMP-mediated lysosomal acidification in bafilomycin A1-treated astrocytes. Glia 69, 1110\u20131125 (2021).","journal-title":"Glia"},{"key":"9504_CR60","doi-asserted-by":"publisher","first-page":"895750","DOI":"10.3389\/fncel.2022.895750","volume":"16","author":"KR Kim","year":"2022","unstructured":"Kim, K. R. et al. Zinc enhances autophagic flux and lysosomal function through transcription factor EB activation and V-ATPase assembly. Front. Cell Neurosci. 16, 895750 (2022).","journal-title":"Front. Cell Neurosci."},{"key":"9504_CR61","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/j.chom.2018.05.012","volume":"23","author":"K Makki","year":"2018","unstructured":"Makki, K., Deehan, E. C., Walter, J. & Backhed, F. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe 23, 705\u2013715 (2018).","journal-title":"Cell Host Microbe"},{"key":"9504_CR62","doi-asserted-by":"publisher","first-page":"2574","DOI":"10.1136\/gutjnl-2021-326575","volume":"71","author":"TE Adolph","year":"2022","unstructured":"Adolph, T. E. & Zhang, J. Diet fuelling inflammatory bowel diseases: preclinical and clinical concepts. Gut 71, 2574\u20132586 (2022).","journal-title":"Gut"},{"key":"9504_CR63","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aao4755","author":"NA Scott","year":"2018","unstructured":"Scott, N. A. et al. Antibiotics induce sustained dysregulation of intestinal T cell immunity by perturbing macrophage homeostasis. Sci. Transl. Med. https:\/\/doi.org\/10.1126\/scitranslmed.aao4755 (2018).","journal-title":"Sci. Transl. Med."},{"key":"9504_CR64","doi-asserted-by":"publisher","first-page":"103293","DOI":"10.1016\/j.ebiom.2021.103293","volume":"66","author":"S Deleu","year":"2021","unstructured":"Deleu, S., Machiels, K., Raes, J., Verbeke, K. & Vermeire, S. Short chain fatty acids and its producing organisms: an overlooked therapy for IBD?. EBioMedicine 66, 103293 (2021).","journal-title":"EBioMedicine"},{"key":"9504_CR65","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00535-016-1242-9","volume":"52","author":"M Sun","year":"2017","unstructured":"Sun, M., Wu, W., Liu, Z. & Cong, Y. Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J. Gastroenterol. 52, 1\u20138 (2017).","journal-title":"J. Gastroenterol."},{"key":"9504_CR66","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.1073\/pnas.1322269111","volume":"111","author":"PV Chang","year":"2014","unstructured":"Chang, P. V., Hao, L., Offermanns, S. & Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl. Acad. Sci. USA 111, 2247\u20132252 (2014).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"9504_CR67","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1038\/nature12721","volume":"504","author":"Y Furusawa","year":"2013","unstructured":"Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446\u2013450 (2013).","journal-title":"Nature"},{"key":"9504_CR68","doi-asserted-by":"publisher","first-page":"841","DOI":"10.3920\/BM2016.0197","volume":"8","author":"A Elce","year":"2017","unstructured":"Elce, A. et al. Butyrate modulating effects on pro-inflammatory pathways in human intestinal epithelial cells. Benef. Microbes 8, 841\u2013847 (2017).","journal-title":"Benef. Microbes"},{"key":"9504_CR69","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-17296-8","volume":"12","author":"M Grouls","year":"2022","unstructured":"Grouls, M. et al. Differential gene expression in iPSC-derived human intestinal epithelial cell layers following exposure to two concentrations of butyrate, propionate and acetate. Sci. Rep. 12, 13988 (2022).","journal-title":"Sci. Rep."},{"key":"9504_CR70","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1093\/cei\/uxab028","volume":"207","author":"C Huang","year":"2022","unstructured":"Huang, C., Du, W., Ni, Y., Lan, G. & Shi, G. The effect of short-chain fatty acids on M2 macrophages polarization in vitro and in vivo. Clin. Exp. Immunol. 207, 53\u201364 (2022).","journal-title":"Clin. Exp. Immunol."},{"key":"9504_CR71","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/s12887-019-1594-4","volume":"19","author":"J Ni","year":"2019","unstructured":"Ni, J. et al. Early antibiotic exposure and development of asthma and allergic rhinitis in childhood. BMC Pediatr. 19, 225 (2019).","journal-title":"BMC Pediatr."},{"key":"9504_CR72","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12020314","author":"Y Lu","year":"2023","unstructured":"Lu, Y. et al. Early-life antibiotic exposure and childhood asthma trajectories: a national population-based birth cohort. Antibiotics https:\/\/doi.org\/10.3390\/antibiotics12020314 (2023).","journal-title":"Antibiotics"},{"key":"9504_CR73","doi-asserted-by":"publisher","first-page":"eabq5126","DOI":"10.1126\/scitranslmed.abq5126","volume":"15","author":"SK Di Simone","year":"2023","unstructured":"Di Simone, S. K., Rudloff, I., Nold-Petry, C. A., Forster, S. C. & Nold, M. F. Understanding respiratory microbiome-immune system interactions in health and disease. Sci. Transl. Med. 15, eabq5126 (2023).","journal-title":"Sci. Transl. Med."},{"key":"9504_CR74","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1016\/j.immuni.2018.04.022","volume":"48","author":"A Trompette","year":"2018","unstructured":"Trompette, A. et al. Dietary fiber confers protection against flu by shaping Ly6c(-) patrolling monocyte hematopoiesis and CD8(+) T cell metabolism. Immunity 48, 992\u20131005 e1008 (2018).","journal-title":"Immunity"},{"key":"9504_CR75","doi-asserted-by":"publisher","first-page":"2934","DOI":"10.1016\/j.celrep.2020.02.013","volume":"30","author":"V Sencio","year":"2020","unstructured":"Sencio, V. et al. Gut dysbiosis during influenza contributes to pulmonary pneumococcal superinfection through altered short-chain fatty acid production. Cell Rep. 30, 2934\u20132947 e2936 (2020).","journal-title":"Cell Rep."},{"key":"9504_CR76","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1053\/j.gastro.2016.06.051","volume":"151","author":"D Li","year":"2016","unstructured":"Li, D. et al. A pleiotropic missense variant in SLC39A8 is associated with Crohn\u2019s disease and human gut microbiome composition. Gastroenterology 151, 724\u2013732 (2016).","journal-title":"Gastroenterology"},{"key":"9504_CR77","first-page":"178","volume":"42","author":"M Li","year":"2016","unstructured":"Li, M. et al. Recent positive selection drives the expansion of a schizophrenia risk nonsynonymous variant at SLC39A8 in Europeans. Schizophr. Bull. 42, 178\u2013190 (2016).","journal-title":"Schizophr. Bull."},{"key":"9504_CR78","doi-asserted-by":"publisher","first-page":"4117","DOI":"10.1093\/hmg\/ddw236","volume":"25","author":"R Zhang","year":"2016","unstructured":"Zhang, R. et al. A blood pressure-associated variant of the SLC39A8 gene influences cellular cadmium accumulation and toxicity. Hum. Mol. Genet. 25, 4117\u20134126 (2016).","journal-title":"Hum. Mol. Genet."},{"key":"9504_CR79","doi-asserted-by":"publisher","first-page":"126483","DOI":"10.1016\/j.jtemb.2020.126483","volume":"60","author":"DL Knoell","year":"2020","unstructured":"Knoell, D. L. et al. Imbalance in zinc homeostasis enhances lung Tissue Loss following cigarette smoke exposure. J. Trace Elem. Med. Biol. 60, 126483 (2020).","journal-title":"J. Trace Elem. Med. Biol."},{"key":"9504_CR80","doi-asserted-by":"publisher","first-page":"e0240707","DOI":"10.1371\/journal.pone.0240707","volume":"16","author":"R Gaurav","year":"2021","unstructured":"Gaurav, R. et al. High-throughput analysis of lung immune cells in a combined murine model of agriculture dust-triggered airway inflammation with rheumatoid arthritis. PLoS One 16, e0240707 (2021).","journal-title":"PLoS One"},{"key":"9504_CR81","doi-asserted-by":"publisher","DOI":"10.1186\/s40635-018-0184-3","volume":"6","author":"SHC Mai","year":"2018","unstructured":"Mai, S. H. C. et al. Body temperature and mouse scoring systems as surrogate markers of death in cecal ligation and puncture sepsis. Intensive Care Med. Exp. 6, 20 (2018).","journal-title":"Intensive Care Med. Exp."},{"key":"9504_CR82","doi-asserted-by":"crossref","unstructured":"Trouplin, V. et al. Bone marrow-derived macrophage production. J. Vis. Exp. 22, e50966 (2013).","DOI":"10.3791\/50966"},{"key":"9504_CR83","doi-asserted-by":"publisher","first-page":"e2217868120","DOI":"10.1073\/pnas.2217868120","volume":"120","author":"J Gustafsson","year":"2023","unstructured":"Gustafsson, J. et al. Generation and analysis of context-specific genome-scale metabolic models derived from single-cell RNA-Seq data. Proc. Natl. Acad. Sci. USA 120, e2217868120 (2023).","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09504-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09504-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09504-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T13:05:29Z","timestamp":1770901529000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-09504-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":83,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["9504"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-09504-8","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]},"assertion":[{"value":"24 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"228"}}