{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T23:40:03Z","timestamp":1785282003452,"version":"3.55.0"},"reference-count":102,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R56 AI114972"],"award-info":[{"award-number":["R56 AI114972"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM109453"],"award-info":[{"award-number":["R01 GM109453"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 GM108563"],"award-info":[{"award-number":["T32 GM108563"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin A (VA) deficiency and diarrheal diseases are both serious public health issues worldwide. VA deficiency is associated with impaired intestinal barrier function and increased risk of mucosal infection-related mortality. The bioactive form of VA, retinoic acid, is a well-known regulator of mucosal integrity. Using Citrobacter rodentium-infected mice as a model for diarrheal diseases in humans, previous studies showed that VA-deficient (VAD) mice failed to clear C. rodentium as compared to their VA-sufficient (VAS) counterparts. However, the distinct intestinal gene responses that are dependent on the host\u2019s VA status still need to be discovered. The mRNAs extracted from the small intestine (SI) and the colon were sequenced and analyzed on three levels: differential gene expression, enrichment, and co-expression. C. rodentium infection interacted differentially with VA status to alter colon gene expression. Novel functional categories downregulated by this pathogen were identified, highlighted by genes related to the metabolism of VA, vitamin D, and ion transport, including improper upregulation of Cl\u2212 secretion and disrupted HCO3\u2212 metabolism. Our results suggest that derangement of micronutrient metabolism and ion transport, together with the compromised immune responses in VAD hosts, may be responsible for the higher mortality to C. rodentium under conditions of inadequate VA.<\/jats:p>","DOI":"10.3390\/nu14081563","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T05:13:08Z","timestamp":1649481188000},"page":"1563","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Transcriptional Profiling of the Small Intestine and the Colon Reveals Modulation of Gut Infection with Citrobacter rodentium According to the Vitamin A Status"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2388-1907","authenticated-orcid":false,"given":"Zhi","family":"Chai","sequence":"first","affiliation":[{"name":"Intercollege Graduate Degree Program in Physiology, The Pennsylvania State University, University Park, PA 16802, USA"},{"name":"Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Lyu","sequence":"additional","affiliation":[{"name":"Intercollege Graduate Degree Program in Bioinformatics and Genomics, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Hsin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9017-0155","authenticated-orcid":false,"given":"Lindsay M.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3558-7660","authenticated-orcid":false,"given":"Veronika","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aswathy","family":"Sebastian","sequence":"additional","affiliation":[{"name":"Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6180-9570","authenticated-orcid":false,"given":"Catharine","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1016\/S0140-6736(12)60560-1","article-title":"Global, regional, and national causes of child mortality: An updated systematic analysis for 2010 with time trends since 2000","volume":"379","author":"Liu","year":"2012","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0140-6736(13)60844-2","article-title":"Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): A prospective, case-control study","volume":"382","author":"Kotloff","year":"2013","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1172\/JCI34005","article-title":"Enteric infections, diarrhea, and their impact on function and development","volume":"118","author":"Petri","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nrmicro2053","article-title":"Enteric infection meets intestinal function: How bacterial pathogens cause diarrhoea","volume":"7","author":"Viswanathan","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","first-page":"197","article-title":"The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000","volume":"81","author":"Kosek","year":"2003","journal-title":"Bull. World Health Organ."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/nrmicro3315","article-title":"Citrobacter rodentium: Infection, inflammation and the microbiota","volume":"12","author":"Collins","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1038\/mi.2017.47","article-title":"Citrobacter rodentium: A model enteropathogen for understanding the interplay of innate and adaptive components of type 3 immunity","volume":"10","author":"Silberger","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1111\/j.1462-5822.2004.00414.x","article-title":"Organ specificity, colonization and clearance dynamics in vivo following oral challenges with the murine pathogen Citrobacter rodentium","volume":"6","author":"Wiles","year":"2004","journal-title":"Cell. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5391","DOI":"10.1128\/IAI.00848-06","article-title":"In vivo bioluminescence imaging of the murine pathogen Citrobacter rodentium","volume":"74","author":"Wiles","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1111\/j.1462-5822.2005.00625.x","article-title":"Citrobacter rodentium of mice and man","volume":"7","author":"Mundy","year":"2005","journal-title":"Cell. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.cell.2015.08.061","article-title":"An IL-23R\/IL-22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses","volume":"163","author":"Sano","year":"2015","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.cell.2015.08.058","article-title":"Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells","volume":"163","author":"Atarashi","year":"2015","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"G39","DOI":"10.1152\/ajpgi.00509.2010","article-title":"Colonic microbiota alters host susceptibility to infectious colitis by modulating inflammation, redox status, and ion transporter gene expression","volume":"301","author":"Ghosh","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1128\/IAI.71.6.3443-3453.2003","article-title":"Host susceptibility to the attaching and effacing bacterial pathogen Citrobacter rodentium","volume":"71","author":"Vallance","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1131S","DOI":"10.1093\/ajcn\/73.6.1131S","article-title":"Microbial modulation of innate defense: Goblet cells and the intestinal mucus layer","volume":"73","author":"Deplancke","year":"2001","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1126\/science.1109051","article-title":"Glycan foraging in vivo by an intestine-adapted bacterial symbiont","volume":"307","author":"Sonnenburg","year":"2005","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bergstrom, K.S., Kissoon-Singh, V., Gibson, D.L., Ma, C., Montero, M., Sham, H.P., Ryz, N., Huang, T., Velcich, A., and Finlay, B.B. (2010). Muc2 protects against lethal infectious colitis by disassociating pathogenic and commensal bacteria from the colonic mucosa. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000902"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gustafsson, J.K., Navabi, N., Rodriguez-Pi\u00f1eiro, A.M., Alomran, A.H., Premaratne, P., Fernandez, H.R., Banerjee, D., Sj\u00f6vall, H., Hansson, G.C., and Lind\u00e9n, S.K. (2013). Dynamic changes in mucus thickness and ion secretion during Citrobacter rodentium infection and clearance. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0084430"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1038\/mi.2015.140","article-title":"The goblet cell-derived mediator RELM-\u03b2 drives spontaneous colitis in Muc2-deficient mice by promoting commensal microbial dysbiosis","volume":"9","author":"Morampudi","year":"2016","journal-title":"Mucosal Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Bergstrom, K.S., Morampudi, V., Chan, J.M., Bhinder, G., Lau, J., Yang, H., Ma, C., Huang, T., Ryz, N., and Sham, H.P. (2015). Goblet cell derived RELM-\u03b2 recruits CD4+ T cells during infectious colitis to promote protective intestinal epithelial cell proliferation. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005108"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Erickson, N.A., Nystr\u00f6m, E.E.L., Mundhenk, L., Arike, L., Glauben, R., Heimesaat, M.M., Fischer, A., Bereswill, S., Birchenough, G.M.H., and Gruber, A.D. (2015). The Goblet Cell Protein Clca1 (Alias mClca3 or Gob-5) Is Not Required for Intestinal Mucus Synthesis, Structure and Barrier Function in Naive or DSS-Challenged Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131991"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.chom.2014.08.017","article-title":"Epithelial IL-22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen","volume":"16","author":"Pham","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2984","DOI":"10.1128\/IAI.00201-15","article-title":"Vitamin A-deficient hosts become nonsymptomatic reservoirs of Escherichia coli-like enteric infections","volume":"83","author":"McDaniel","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/mi.2014.94","article-title":"Dysbiosis caused by vitamin D receptor deficiency confers colonization resistance to Citrobacter rodentium through modulation of innate lymphoid cells","volume":"8","author":"Chen","year":"2015","journal-title":"Mucosal Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3090","DOI":"10.3389\/fimmu.2018.03090","article-title":"Retinoic acid mediated clearance of Citrobacter rodentium in vitamin A deficient mice requires CD11b+ and T Cells","volume":"9","author":"Snyder","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature04754","article-title":"Transforming growth factor-\u03b2 induces development of the T H 17 lineage","volume":"441","author":"Mangan","year":"2006","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.immuni.2010.12.009","article-title":"CD4+ lymphoid tissue-inducer cells promote innate immunity in the gut","volume":"34","author":"Sonnenberg","year":"2011","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1128\/IAI.00225-09","article-title":"Decreased expression of colonic Slc26a3 and carbonic anhydrase iv as a cause of fatal infectious diarrhea in mice","volume":"77","author":"Borenshtein","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"R122","DOI":"10.1186\/gb-2008-9-8-r122","article-title":"Diarrhea as a cause of mortality in a mouse model of infectious colitis","volume":"9","author":"Borenshtein","year":"2008","journal-title":"Genome Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1146\/annurev.physiol.62.1.535","article-title":"Chloride secretion by the intestinal epithelium: Molecular basis and regulatory aspects","volume":"62","author":"Barrett","year":"2000","journal-title":"Annu. Rev. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1177\/039463200902200108","article-title":"Immunomodulatory effects of 1, 25-dihydroxyvitamin D3 on TH1\/TH2 cytokines in inflammatory bowel disease: An in vitro study","volume":"22","author":"Ardizzone","year":"2009","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.intimp.2007.09.016","article-title":"1, 25-dihydroxyvitamin D3 and dexamethasone increase interleukin-10 production in CD4+ T cells from patients with Crohn\u2019s disease","volume":"7","author":"Bartels","year":"2007","journal-title":"Int. Immunopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.imlet.2010.03.006","article-title":"Efficacy of a potent and safe vitamin D receptor agonist for the treatment of inflammatory bowel disease","volume":"131","author":"Laverny","year":"2010","journal-title":"Immunol. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0006-2952(00)00564-5","article-title":"Suppressive effect of 1, 25-dihydroxyvitamin D3 and its analogues EB 1089 and KH 1060 on T lymphocyte proliferation in active ulcerative colitis","volume":"61","author":"Stio","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/ibd.20354","article-title":"Vitamin D derivatives induce apoptosis and downregulate ICAM-1 levels in peripheral blood mononuclear cells of inflammatory bowel disease patients","volume":"14","author":"Martinesi","year":"2008","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1194\/jlr.M600528-JLR200","article-title":"Model-based compartmental analysis indicates a reduced mobilization of hepatic vitamin A during inflammation in rats","volume":"48","author":"Gieng","year":"2007","journal-title":"J. Lipid Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/S0022-2275(20)42007-3","article-title":"Effects of acute inflammation on plasma retinol, retinol-binding protein, and its mRNA in the liver and kidneys of vitamin A-sufficient rats","volume":"37","author":"Rosales","year":"1996","journal-title":"J. Lipid Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3945\/jn.113.186569","article-title":"Streptococcus pneumoniae-induced pneumonia and Citrobacter rodentium-induced gut infection differentially alter vitamin A concentrations in the lung and liver of mice","volume":"144","author":"Restori","year":"2014","journal-title":"J. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7115","DOI":"10.4049\/jimmunol.181.10.7115","article-title":"IL-15 links TLR2\/1-induced macrophage differentiation to the vitamin D-dependent antimicrobial pathway","volume":"181","author":"Krutzik","year":"2008","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1126\/science.1123933","article-title":"Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response","volume":"311","author":"Liu","year":"2006","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1359\/JBMR.050908","article-title":"Immune regulation of 25-hydroxyvitamin-D3-1\u03b1-hydroxylase in human monocytes","volume":"21","author":"Stoffels","year":"2006","journal-title":"J. Bone Miner. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1136\/bmj.306.6874.366","article-title":"Vitamin A supplementation in infectious diseases: A meta-analysis","volume":"306","author":"Glasziou","year":"1993","journal-title":"Br. Med. J."},{"key":"ref_43","first-page":"71","article-title":"The pleiotropic role of vitamin A in regulating mucosal immunity","volume":"33","author":"Sirisinha","year":"2015","journal-title":"Asian Pac. J. Allergy Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"108814","DOI":"10.1016\/j.jnutbio.2021.108814","article-title":"RNAseq studies reveal distinct transcriptional response to vitamin A deficiency in small intestine versus colon, uncovering novel vitamin A-regulated genes","volume":"98","author":"Chai","year":"2021","journal-title":"J. Nutr. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2857S","DOI":"10.1093\/jn\/132.9.2857S","article-title":"Extent of vitamin A deficiency among preschool children and women of reproductive age","volume":"132","author":"West","year":"2002","journal-title":"J. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"388","DOI":"10.4049\/jimmunol.142.2.388","article-title":"Characterization of a helper T lymphocyte defect in vitamin A-deficient mice","volume":"142","author":"Carman","year":"1989","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1093\/jn\/117.5.857","article-title":"Impaired immunity in vitamin A-deficient mice","volume":"117","author":"Smith","year":"1987","journal-title":"J. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5878","DOI":"10.1073\/pnas.84.16.5878","article-title":"Contrasting impairments in IgM and IgG responses of vitamin A-deficient mice","volume":"84","author":"Smith","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: A flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"FeatureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). WGCNA: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2007). Eigengene networks for studying the relationships between co-expression modules. BMC Syst. Biol., 1.","DOI":"10.1186\/1752-0509-1-54"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics A J. Integr. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4528","DOI":"10.1128\/IAI.00953-15","article-title":"Bioluminescent Imaging Reveals Novel Patterns of Colonization and Invasion in Systemic Escherichia coli K1 Experimental Infection in the Neonatal Rat","volume":"83","author":"Witcomb","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S1286-4579(01)01387-9","article-title":"Molecular pathogenesis of Citrobacter rodentium and transmissible murine colonic hyperplasia","volume":"3","author":"Luperchio","year":"2001","journal-title":"Microbes Infect."},{"key":"ref_59","first-page":"318","article-title":"Intestinal Muc2 mucin O-glycosylation is affected by microbiota and regulated by differential expression of glycosyltranferases","volume":"27","author":"Arike","year":"2017","journal-title":"Glycobiology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1126\/science.273.5280.1380","article-title":"A model of host-microbial interactions in an open mammalian ecosystem","volume":"273","author":"Bry","year":"1996","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1254009","DOI":"10.1126\/science.1254009","article-title":"Innate lymphoid cells regulate intestinal epithelial cell glycosylation","volume":"345","author":"Goto","year":"2014","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/nature13823","article-title":"Rapid fucosylation of intestinal epithelium sustains host\u2013commensal symbiosis in sickness","volume":"514","author":"Pickard","year":"2014","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1111\/j.1462-5822.2007.01071.x","article-title":"MyD88 signalling plays a critical role in host defence by controlling pathogen burden and promoting epithelial cell homeostasis during Citrobacter rodentium-induced colitis","volume":"10","author":"Gibson","year":"2008","journal-title":"Cell. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1196\/annals.1443.020","article-title":"Toll-like receptor and RIG-1-like receptor signaling","volume":"1143","author":"Kawai","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"566","DOI":"10.4049\/jimmunol.179.1.566","article-title":"TLR signaling mediated by MyD88 is required for a protective innate immune response by neutrophils to Citrobacter rodentium","volume":"179","author":"Lebeis","year":"2007","journal-title":"J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5077","DOI":"10.1128\/IAI.71.9.5077-5086.2003","article-title":"Central role for B lymphocytes and CD4+ T cells in immunity to infection by the attaching and effacing pathogen Citrobacter rodentium","volume":"71","author":"Simmons","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1128\/IAI.70.4.2070-2081.2002","article-title":"Mice lacking T and B lymphocytes develop transient colitis and crypt hyperplasia yet suffer impaired bacterial clearance during Citrobacter rodentium infection","volume":"70","author":"Vallance","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1128\/IAI.67.6.3031-3039.1999","article-title":"Citrobacter rodentium infection in mice elicits a mucosal Th1 cytokine response and lesions similar to those in murine inflammatory bowel disease","volume":"67","author":"Higgins","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.4049\/jimmunol.168.4.1804","article-title":"Impaired resistance and enhanced pathology during infection with a noninvasive, attaching-effacing enteric bacterial pathogen, Citrobacter rodentium, in mice lacking IL-12 or IFN-\u03b3","volume":"168","author":"Simmons","year":"2002","journal-title":"J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.immuni.2008.11.009","article-title":"Differential roles of interleukin-17A and-17F in host defense against mucoepithelial bacterial infection and allergic responses","volume":"30","author":"Ishigame","year":"2009","journal-title":"Immunity"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1084\/jem.20061308","article-title":"Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides","volume":"203","author":"Liang","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.cell.2009.09.033","article-title":"Induction of intestinal Th17 cells by segmented filamentous bacteria","volume":"139","author":"Ivanov","year":"2009","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nrmicro2538","article-title":"Mucin dynamics and enteric pathogens","volume":"9","author":"McGuckin","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/nm.2391","article-title":"Identification of an innate T helper type 17 response to intestinal bacterial pathogens","volume":"17","author":"Geddes","year":"2011","journal-title":"Nat. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/nm1720","article-title":"Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens","volume":"14","author":"Zheng","year":"2008","journal-title":"Nat. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"831","DOI":"10.3892\/mmr.2014.1898","article-title":"Cytokine IL-6 is required in Citrobacter rodentium infection-induced intestinal Th17 responses and promotes IL-22 expression in inflammatory bowel disease","volume":"9","author":"Li","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.4049\/jimmunol.1001672","article-title":"Expression of retinaldehyde dehydrogenase enzymes in mucosal dendritic cells and gut-draining lymph node stromal cells is controlled by dietary vitamin A","volume":"186","author":"Molenaar","year":"2011","journal-title":"J. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/00001574-200103000-00015","article-title":"Vitamin A: Recent advances in the biotransformation, transport, and metabolism of retinoids","volume":"17","author":"Ross","year":"2001","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1096\/fj.00-0061com","article-title":"Regulation of CYP26 (cytochrome P450RAI) mRNA expression and retinoic acid metabolism by retinoids and dietary vitamin A in liver of mice and rats","volume":"14","author":"Yamamoto","year":"2000","journal-title":"FASEB J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1600576","DOI":"10.1002\/mnfr.201600576","article-title":"Lack of \u03b2, \u03b2-carotene-9\u2032, 10\u2032-oxygenase 2 leads to hepatic mitochondrial dysfunction and cellular oxidative stress in mice","volume":"61","author":"Wu","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.mce.2007.09.010","article-title":"LIF removal increases CRABPI and CRABPII transcripts in embryonic stem cells cultured in retinol or 4-oxoretinol","volume":"280","author":"Lane","year":"2008","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_82","first-page":"152","article-title":"Physiological insights into all-trans-retinoic acid biosynthesis","volume":"1821","author":"Napoli","year":"2012","journal-title":"Biochim. Biophys. Acta BBA Mol. Cell Biol. Lipids"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"G601","DOI":"10.1152\/ajpgi.00231.2013","article-title":"Recent advances in transport of water-soluble vitamins in organs of the digestive system: A focus on the colon and the pancreas","volume":"305","author":"Said","year":"2013","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Li, Y., Wei, C.-H., Hodges, J.K., Green, M.H., and Ross, A.C. (2021). Priming with Retinoic Acid, an Active Metabolite of Vitamin A, Increases Vitamin A Uptake in the Small Intestine of Neonatal Rats. Nutrients, 13.","DOI":"10.3390\/nu13124275"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7142","DOI":"10.3748\/wjg.v21.i23.7142","article-title":"Molecular aspects of intestinal calcium absorption","volume":"21","author":"Guizzardi","year":"2015","journal-title":"World J. Gastroenterol. WJG"},{"key":"ref_86","first-page":"245","article-title":"The extracellular calcium-sensing receptor in the intestine: Evidence for regulation of colonic absorption, secretion, motility, and immunity","volume":"7","author":"Tang","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.tem.2019.04.005","article-title":"Aligning the Paradoxical Role of Vitamin D in Gastrointestinal Immunity","volume":"30","author":"Cantorna","year":"2019","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2019.00001","article-title":"Vitamin D is required for ILC3 derived IL-22 and protection from Citrobacter rodentium infection","volume":"10","author":"Lin","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1128\/IAI.74.5.2522-2536.2006","article-title":"Toll-like receptor 4 contributes to colitis development but not to host defense during Citrobacter rodentium infection in mice","volume":"74","author":"Khan","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.1128\/IAI.01810-06","article-title":"Development of fatal colitis in FVB mice infected with Citrobacter rodentium","volume":"75","author":"Borenshtein","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"C351","DOI":"10.1152\/ajpcell.1999.277.3.C351","article-title":"Innate mechanisms of epithelial host defense: Spotlight on intestine","volume":"277","author":"Hecht","year":"1999","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/ng1196-316","article-title":"Mutations of the Down\u2013regulated in adenoma (DRA) gene cause congenital chloride diarrhoea","volume":"14","author":"Haila","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1053\/j.gastro.2017.08.024","article-title":"Activation of Nuclear Factor\u2212 \u03baB by Tumor Necrosis Factor in Intestinal Epithelial Cells and Mouse Intestinal Epithelia Reduces Expression of the Chloride Transporter SLC26A3","volume":"153","author":"Kumar","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/s00424-014-1559-2","article-title":"Anoctamins support calcium-dependent chloride secretion by facilitating calcium signaling in adult mouse intestine","volume":"467","author":"Schreiber","year":"2015","journal-title":"Pfl\u00fcgers Arch. Eur. J. Physiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1146\/annurev.physiol.67.031103.153004","article-title":"Molecular physiology of intestinal N+\/H+ exchange","volume":"67","author":"Zachos","year":"2005","journal-title":"Annu. Rev. Physiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1152\/physrev.00026.2001","article-title":"Electrolyte transport in the mammalian colon: Mechanisms and implications for disease","volume":"82","author":"Kunzelmann","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"17367","DOI":"10.1074\/jbc.M100296200","article-title":"Calcineurin homologous protein as an essential cofactor for Na+\/H+ exchangers","volume":"276","author":"Pang","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/j.1469-7793.1999.209aa.x","article-title":"A novel role for carbonic anhydrase: Cytoplasmic pH gradient dissipation in mouse small intestinal enterocytes","volume":"516","author":"Stewart","year":"1999","journal-title":"J. Physiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1053\/gast.1996.v111.agast961111358","article-title":"Acid-base effects on colonic electrolyte transport revisited","volume":"111","author":"Charney","year":"1996","journal-title":"Gastroenterology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"C591","DOI":"10.1152\/ajpcell.00281.2007","article-title":"Antibody-independent localization of the electroneutral Na+-HCO3\u2212cotransporter NBCn1 (slc4a7) in mice","volume":"294","author":"Boedtkjer","year":"2008","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1113\/jphysiol.2011.226506","article-title":"The electroneutral Na+:HCO3\u2212cotransporter NBCn1 is a major pHi regulator in murine duodenum","volume":"590","author":"Chen","year":"2012","journal-title":"J. Physiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1096\/fasebj.27.1_supplement.730.4","article-title":"The electroneutral Na+HCO3\u2212 cotransporter NBCn1 plays an essential role in duodenal acid\/base balance and colonic mucus layer build-up in anaestetised mice","volume":"27","author":"Seidler","year":"2013","journal-title":"Faseb J."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/8\/1563\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:50:47Z","timestamp":1760136647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/8\/1563"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,8]]},"references-count":102,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["nu14081563"],"URL":"https:\/\/doi.org\/10.3390\/nu14081563","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,8]]}}}