{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T23:41:30Z","timestamp":1783467690083,"version":"3.55.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK114478"],"award-info":[{"award-number":["DK114478"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Johns Hopkins Specialized Center for Research Excellence in Sex Differences","award":["U54AG062333"],"award-info":[{"award-number":["U54AG062333"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>A pathogenic mutation in the manganese transporter ZIP8 (A391T; rs13107325) increases the risk of Crohn\u2019s disease. ZIP8 regulates manganese homeostasis and given the shared need for metals between the host and resident microbes, there has been significant interest in alterations of the microbiome in carriers of ZIP8 A391T. Prior studies have not examined the ileal microbiome despite associations between ileal disease and ZIP8 A391T.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Here, we used the Pediatric Risk Stratification Study (RISK) cohort to perform a secondary analysis of 16S ribosomal RNA gene sequencing data obtained from ileal and rectal mucosa to study associations between ZIP8 A391T carrier status and microbiota composition.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found sequence variants mapping to Veillonella were decreased in the ileal mucosa of ZIP8 A391T carriers. Prior human studies have demonstrated the sensitivity of Veillonella to bile acid abundance. We therefore hypothesized that bile acid homeostasis is differentially regulated in carriers of ZIP8 A391T. Using a mouse model of ZIP8 A391T, we demonstrate an increase in total bile acids in the liver and stool and decreased fibroblast growth factor 15 (Fgf15) signaling, consistent with our hypothesis. We confirmed dysregulation of FGF19 in the 1000IBD cohort, finding that plasma FGF19 levels are lower in ZIP8 A391T carriers with ileocolonic Crohn\u2019s disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In the search for genotype-specific therapeutic paradigms for patients with Crohn\u2019s disease, these data suggest targeting the FGF19 pathway in ZIP8 A391T carriers. Aberrant bile acid metabolism may precede development of Crohn\u2019s disease and prioritize study of the interactions between manganese homeostasis, bile acid metabolism and signaling, and complicated ileal Crohn\u2019s disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izae003","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T19:33:09Z","timestamp":1706643189000},"page":"1379-1388","source":"Crossref","is-referenced-by-count":13,"title":["Crohn\u2019s Disease\u2013Associated Pathogenic Mutation in the Manganese Transporter ZIP8 Shifts the Ileal and Rectal Mucosal Microbiota Implicating Aberrant Bile Acid Metabolism"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0947-3686","authenticated-orcid":false,"given":"Kristi","family":"Briggs","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vartika","family":"Tomar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Ollberding","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati College of Medicine , Cincinnati, OH , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Haberman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati College of Medicine , Cincinnati, OH , USA"},{"name":"Department of Pediatrics, Sheba Medical Center, Tel-Hashomer, affiliated with Tel Aviv University , Tel Aviv , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arno R","family":"Bourgonje","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"},{"name":"Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixian","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands"},{"name":"Department of Gastroenterology, First Affiliated Hospital, Sun Yat-Sen University , Guangzhou, Guangdong , China"},{"name":"Institute of Precision Medicine, First Affiliated Hospital, Sun Yat-Sen University , Guangzhou, Guangdong , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Chaaban","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, MD , 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