{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:06:18Z","timestamp":1789153578973,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014558","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000}}],"reference-count":101,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100024057","name":"School of Medicine and Health Sciences","doi-asserted-by":"publisher","award":["Sartup fund (20344-8015)"],"award-info":[{"award-number":["Sartup fund (20344-8015)"]}],"id":[{"id":"10.13039\/100024057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100024057","name":"School of Medicine and Health Sciences","doi-asserted-by":"publisher","award":["Dean's Meritorious Award"],"award-info":[{"award-number":["Dean's Meritorious Award"]}],"id":[{"id":"10.13039\/100024057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM113123"],"award-info":[{"award-number":["P20GM113123"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Approximately 90 million American adults are hypercholesterolemic, with an estimated 43 million individuals either already using or eligible to receive cholesterol-lowering medications, such as bile acid sequestrants. Although bile acid sequestrants have demonstrated therapeutic efficacy in lowering cholesterol levels in individuals with hypercholesterolemia, their impact on intestinal homeostasis in healthy individuals and those with enteric microbial infections remains unclear. We set out to investigate the potential effects of bile acid sequestration on mucosal immune responses and to evaluate how enteric microbial pathogens colonize the small intestine of mice\n                    <jats:italic>in vivo<\/jats:italic>\n                    . We also examined how bile acid sequestration affected intestinal microbial ecosystems before and during enteric infection. We found that bile acid sequestration increased resistance to enteric infection, and this phenotype required farnesoid X receptor (FXR) in myeloid cells. We observed significantly increased diversity and richness in the gut microbiome of mice that were administered a bile acid sequestrant that correlated with enhanced resistance to enteric infection, suggesting that bile acids may function as limiting factors for the diversity and richness of the gut microbiome in health and disease. Notably, the antibiotic-driven depletion of the gut microbiome led to significantly increased susceptibility to infection with both\n                    <jats:italic>Giardia duodenalis<\/jats:italic>\n                    and\n                    <jats:italic>Giardia muris<\/jats:italic>\n                    . Our findings reveal a previously overlooked role for bile acid sequestrants in the regulation of the gut microbiome as well as host resistance to enteric infections. Bile acid sequestration and the subsequent blockade of pathways downstream of bile acid signaling may modulate host immunity during enteric infections, potentially leading to an altered gut microbiome in individuals taking bile acid sequestrants to lower blood cholesterol.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014558","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:46:58Z","timestamp":1788889618000},"page":"e1014558","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bile acid sequestration reveals microbiome remodeling that dominates FXR signaling to shape host responses to enteric infection"],"prefix":"10.1371","volume":"22","author":[{"given":"Anahita","family":"Mansouripour","sequence":"first","affiliation":[{"name":"School of Medicine and Health Sciences, University of North Dakota","place":["Grand Forks, North Dakota, United States of America"],"department":["Department of Biomedical Sciences"]},{"name":"School of Medicine and Health Sciences, University of North Dakota","place":["Grand Forks, North Dakota, United States of America"],"department":["Laboratory of Mucosal Immunology, Department of Biomedical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drew R.","family":"Seeger","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Sciences, University of North Dakota","place":["Grand Forks, North Dakota, United States of America"],"department":["Department of Biomedical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith","family":"Parmer","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Sciences, University of North Dakota","place":["Grand Forks, North Dakota, United States of America"],"department":["Department of Biomedical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peddanna","family":"Kotha","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Sciences, University of North Dakota","place":["Grand Forks, North Dakota, United States of America"],"department":["Department of Biomedical Sciences"]},{"name":"School of Medicine and Health Sciences, University of North Dakota","place":["Grand Forks, North Dakota, United States of America"],"department":["Laboratory of Mucosal Immunology, Department of Biomedical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton M.","family":"Golovko","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Sciences, University of North Dakota","place":["Grand Forks, North Dakota, United States of America"],"department":["Department of Biomedical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail Y.","family":"Golovko","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Sciences, University of North Dakota","place":["Grand Forks, North Dakota, United States of America"],"department":["Department of Biomedical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-3830","authenticated-orcid":true,"given":"Shahram","family":"Solaymani-Mohammadi","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Sciences, University of North Dakota","place":["Grand Forks, North Dakota, United States of America"],"department":["Department of Biomedical Sciences"]},{"name":"School of Medicine and Health Sciences, University of North Dakota","place":["Grand Forks, North Dakota, United States of America"],"department":["Laboratory of Mucosal Immunology, Department of Biomedical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"issue":"47","key":"ppat.1014558.ref001","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.15585\/mmwr.mm6447a1","article-title":"Prevalence of Cholesterol Treatment Eligibility and Medication Use Among Adults--United States, 2005-2012","volume":"64","author":"C Mercado","year":"2015","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"15","key":"ppat.1014558.ref002","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1056\/NEJMoa1315665","article-title":"Application of new cholesterol guidelines to a population-based sample","volume":"370","author":"MJ Pencina","year":"2014","journal-title":"N Engl J Med"},{"key":"ppat.1014558.ref003","article-title":"HDL, National Health and Nutrition Examination Survey: Total and High-density Lipoprotein Cholesterol in Adults: United States, 2015e2016. 290","author":"M Carroll","year":"2017"},{"issue":"9","key":"ppat.1014558.ref004","doi-asserted-by":"crossref","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association","volume":"141","author":"SS Virani","year":"2020","journal-title":"Circulation"},{"key":"ppat.1014558.ref005","article-title":"Bile acids and metabolic regulation: mechanisms and clinical responses to bile acid sequestration","author":"B Staels","year":"2009","journal-title":"Diabetes Care"},{"issue":"6","key":"ppat.1014558.ref006","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1194\/jlr.R054114","article-title":"Intestinal transport and metabolism of bile acids","volume":"56","author":"PA Dawson","year":"2015","journal-title":"J Lipid Res"},{"issue":"5","key":"ppat.1014558.ref007","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/0092-8674(95)90530-8","article-title":"Identification of a nuclear receptor that is activated by farnesol metabolites","volume":"81","author":"BM Forman","year":"1995","journal-title":"Cell"},{"key":"ppat.1014558.ref008","doi-asserted-by":"crossref","first-page":"111618","DOI":"10.1016\/j.mce.2022.111618","article-title":"Discovery of farnesoid X receptor and its role in bile acid metabolism","volume":"548","author":"JYL Chiang","year":"2022","journal-title":"Mol Cell Endocrinol"},{"issue":"11","key":"ppat.1014558.ref009","doi-asserted-by":"crossref","first-page":"9435","DOI":"10.1074\/jbc.M209706200","article-title":"A G protein-coupled receptor responsive to bile acids","volume":"278","author":"Y Kawamata","year":"2003","journal-title":"J Biol Chem"},{"issue":"5","key":"ppat.1014558.ref010","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/S0006-291X(02)02550-0","article-title":"Identification of membrane-type receptor for bile acids (M-BAR)","volume":"298","author":"T Maruyama","year":"2002","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"ppat.1014558.ref011","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41392-024-01811-6","article-title":"Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets","volume":"9","author":"JS Fleishman","year":"2024","journal-title":"Signal Transduct Target Ther"},{"issue":"20","key":"ppat.1014558.ref012","doi-asserted-by":"crossref","first-page":"7421","DOI":"10.1073\/pnas.1323599111","article-title":"Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut","volume":"111","author":"SA Joyce","year":"2014","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"4","key":"ppat.1014558.ref013","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.immuni.2016.09.008","article-title":"Bile Acids Control Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome","volume":"45","author":"C Guo","year":"2016","journal-title":"Immunity"},{"issue":"1","key":"ppat.1014558.ref014","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12967-024-05873-6","article-title":"Gut bacteria Prevotellaceae related lithocholic acid metabolism promotes colonic inflammation","volume":"23","author":"L Chen","year":"2025","journal-title":"J Transl Med"},{"issue":"7798","key":"ppat.1014558.ref015","doi-asserted-by":"crossref","DOI":"10.1038\/s41586-020-2030-5","article-title":"Author Correction: Bile acid metabolites control TH17 and Treg cell differentiation","volume":"579","author":"S Hang","year":"2020","journal-title":"Nature"},{"issue":"7809","key":"ppat.1014558.ref016","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41586-020-2193-0","article-title":"Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells","volume":"581","author":"C Campbell","year":"2020","journal-title":"Nature"},{"issue":"12","key":"ppat.1014558.ref017","doi-asserted-by":"crossref","first-page":"101342","DOI":"10.1016\/j.cpcardiol.2022.101342","article-title":"Lipid Lowering Therapy: An Era Beyond Statins","volume":"47","author":"T Abdul-Rahman","year":"2022","journal-title":"Curr Probl Cardiol"},{"issue":"16","key":"ppat.1014558.ref018","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1001\/archinte.159.16.1893","article-title":"Colesevelam hydrochloride (cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects","volume":"159","author":"MH Davidson","year":"1999","journal-title":"Arch Intern Med"},{"issue":"4","key":"ppat.1014558.ref019","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1161\/CIRCGENETICS.114.000952","article-title":"Effect of Bile Acid Sequestrants on the Risk of Cardiovascular Events: A Mendelian Randomization Analysis","volume":"8","author":"CARDIoGRAMplusC4D Consortium","year":"2015","journal-title":"Circ Cardiovasc Genet"},{"key":"ppat.1014558.ref020","article-title":"Bile acid sequestrants: mechanisms of action on bile acid and cholesterol metabolism","author":"K Einarsson","year":"1991","journal-title":"Eur J Clin Pharmacol"},{"issue":"10","key":"ppat.1014558.ref021","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.cgh.2013.04.029","article-title":"Methods for diagnosis of bile acid malabsorption in clinical practice","volume":"11","author":"P Vijayvargiya","year":"2013","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"3","key":"ppat.1014558.ref022","doi-asserted-by":"crossref","first-page":"332","DOI":"10.5009\/gnl14397","article-title":"Bile Acid diarrhea: prevalence, pathogenesis, and therapy","volume":"9","author":"M Camilleri","year":"2015","journal-title":"Gut Liver"},{"issue":"2","key":"ppat.1014558.ref023","doi-asserted-by":"crossref","DOI":"10.1152\/ajpgi.00353.2024","article-title":"Bile acid sequestrant inhibits gluconeogenesis via inducing hepatic cysteine dioxygenase type 1 to reduce cysteine availability","volume":"328","author":"DJ Matye","year":"2025","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"1","key":"ppat.1014558.ref024","doi-asserted-by":"crossref","DOI":"10.1152\/ajpgi.00476.2020","article-title":"Dynamics of the enterohepatic circulation of bile acids in healthy humans","volume":"321","author":"F Stellaard","year":"2021","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"5","key":"ppat.1014558.ref025","doi-asserted-by":"crossref","DOI":"10.1152\/ajpgi.00308.2020","article-title":"Metabolic consequences of ileal interruption of the enterohepatic circulation of bile acids","volume":"319","author":"IP van de Peppel","year":"2020","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"4","key":"ppat.1014558.ref026","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.cmet.2005.09.001","article-title":"Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis","volume":"2","author":"T Inagaki","year":"2005","journal-title":"Cell Metab"},{"issue":"13","key":"ppat.1014558.ref027","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1101\/gad.1083503","article-title":"Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis","volume":"17","author":"JA Holt","year":"2003","journal-title":"Genes Dev"},{"key":"ppat.1014558.ref028","doi-asserted-by":"crossref","first-page":"1214136","DOI":"10.3389\/fpara.2023.1214136","article-title":"Chronic small intestinal helminth infection perturbs bile acid homeostasis and disrupts bile acid signaling in the murine small intestine","volume":"2","author":"JM Lane","year":"2023","journal-title":"Front Parasitol"},{"issue":"565","key":"ppat.1014558.ref029","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aay7019","article-title":"Disturbed gut microbiota and bile homeostasis in Giardia-infected mice contributes to metabolic dysregulation and growth impairment","volume":"12","author":"A Riba","year":"2020","journal-title":"Sci Transl Med"},{"issue":"6","key":"ppat.1014558.ref030","doi-asserted-by":"crossref","first-page":"3342","DOI":"10.1128\/IAI.00169-06","article-title":"Bile acids enhance invasiveness of Cryptosporidium spp. into cultured cells","volume":"74","author":"H Feng","year":"2006","journal-title":"Infect Immun"},{"issue":"12","key":"ppat.1014558.ref031","doi-asserted-by":"crossref","first-page":"3376","DOI":"10.1038\/s41564-024-01862-z","article-title":"Enteric bacterial infection stimulates remodelling of bile metabolites to promote intestinal homeostasis","volume":"9","author":"T Zhang","year":"2024","journal-title":"Nat Microbiol"},{"issue":"1","key":"ppat.1014558.ref032","doi-asserted-by":"crossref","DOI":"10.1128\/mSphere.00045-15","article-title":"Antibiotic-Induced Alterations of the Gut Microbiota Alter Secondary Bile Acid Production and Allow for Clostridium difficile Spore Germination and Outgrowth in the Large Intestine","volume":"1","author":"CM Theriot","year":"2016","journal-title":"mSphere"},{"issue":"6676","key":"ppat.1014558.ref033","doi-asserted-by":"crossref","DOI":"10.1126\/science.adj3502","article-title":"Microbiome diversity protects against pathogens by nutrient blocking","volume":"382","author":"F Spragge","year":"2023","journal-title":"Science"},{"issue":"7","key":"ppat.1014558.ref034","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1038\/s41564-024-01710-0","article-title":"Klebsiella oxytoca inhibits Salmonella infection through multiple microbiota-context-dependent mechanisms","volume":"9","author":"L Osbelt","year":"2024","journal-title":"Nat Microbiol"},{"issue":"7","key":"ppat.1014558.ref035","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.4049\/jimmunol.1100606","article-title":"Host immunity and pathogen strain contribute to intestinal disaccharidase impairment following gut infection","volume":"187","author":"S Solaymani-Mohammadi","year":"2011","journal-title":"J Immunol"},{"issue":"2","key":"ppat.1014558.ref036","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/mi.2012.80","article-title":"Regulation of intestinal epithelial cell cytoskeletal remodeling by cellular immunity following gut infection","volume":"6","author":"S Solaymani-Mohammadi","year":"2013","journal-title":"Mucosal Immunol"},{"issue":"4","key":"ppat.1014558.ref037","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1086\/315409","article-title":"The role of normal flora in Giardia lamblia infections in mice","volume":"181","author":"SM Singer","year":"2000","journal-title":"J Infect Dis"},{"issue":"4","key":"ppat.1014558.ref038","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1128\/IAI.00074-16","article-title":"Complement Activation by Giardia duodenalis Parasites through the Lectin Pathway Contributes to Mast Cell Responses and Parasite Control","volume":"84","author":"E Li","year":"2016","journal-title":"Infect Immun"},{"key":"ppat.1014558.ref039","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.mimet.2017.07.004","article-title":"Stool antigen immunodetection for diagnosis of Giardia duodenalis infection in human subjects with HIV and cancer","volume":"141","author":"M Nooshadokht","year":"2017","journal-title":"J Microbiol Methods"},{"issue":"12","key":"ppat.1014558.ref040","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1093\/cid\/ciy372","article-title":"Giardia\/Cryptosporidium QUIK CHEK assay is more specific than quantitative polymerase chain reaction for rapid point-of-care diagnosis of cryptosporidiosis in infants in Bangladesh","volume":"67","author":"M Kabir","year":"2018","journal-title":"Clin Infect Dis"},{"issue":"11","key":"ppat.1014558.ref041","doi-asserted-by":"crossref","first-page":"100452","DOI":"10.1016\/j.jlr.2023.100452","article-title":"Exogenous oxygen is required for prostanoid induction under brain ischemia as evidence for a novel regulatory mechanism","volume":"64","author":"DR Seeger","year":"2023","journal-title":"J Lipid Res"},{"issue":"1","key":"ppat.1014558.ref042","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/s13071-023-05821-1","article-title":"A shotgun metagenomic analysis of the fecal microbiome in humans infected with Giardia duodenalis","volume":"16","author":"BA McGregor","year":"2023","journal-title":"Parasit Vectors"},{"issue":"2","key":"ppat.1014558.ref043","doi-asserted-by":"crossref","first-page":"103706","DOI":"10.1016\/j.xpro.2025.103706","article-title":"Protocol for the generation and assessment of functional macrophages from mouse bone marrow cells","volume":"6","author":"A Scafidi","year":"2025","journal-title":"STAR Protoc"},{"issue":"1","key":"ppat.1014558.ref044","doi-asserted-by":"crossref","first-page":"100246","DOI":"10.1016\/j.xpro.2020.100246","article-title":"Preparation and culture of bone marrow-derived macrophages from mice for functional analysis","volume":"2","author":"G Toda","year":"2020","journal-title":"STAR Protoc"},{"issue":"2","key":"ppat.1014558.ref045","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007614","article-title":"Interleukin 21 collaborates with interferon-\u03b3 for the optimal expression of interferon-stimulated genes and enhances protection against enteric microbial infection","volume":"15","author":"S Solaymani-Mohammadi","year":"2019","journal-title":"PLoS Pathog"},{"issue":"4","key":"ppat.1014558.ref046","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1093\/jleuko\/qiae069","article-title":"The IL-21\/IL-21R signaling axis regulates CD4+ T-cell responsiveness to IL-12 to promote bacterial-induced colitis","volume":"116","author":"S Solaymani-Mohammadi","year":"2024","journal-title":"J Leukoc Biol"},{"issue":"5","key":"ppat.1014558.ref047","doi-asserted-by":"crossref","first-page":"908","DOI":"10.2307\/3284287","article-title":"Mast cell hyperplasia and increased macromolecular uptake in an animal model of giardiasis","volume":"83","author":"JA Hardin","year":"1997","journal-title":"J Parasitol"},{"issue":"8","key":"ppat.1014558.ref048","article-title":"Giardia duodenalis induces paracellular bacterial translocation and causes postinfectious visceral hypersensitivity","volume":"310","author":"MCM Halliez","year":"2016","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"1","key":"ppat.1014558.ref049","doi-asserted-by":"crossref","first-page":"18842","DOI":"10.1038\/s41598-021-98262-8","article-title":"High-fat diet increases the severity of Giardia infection in association with low-grade inflammation and gut microbiota dysbiosis","volume":"11","author":"T Allain","year":"2021","journal-title":"Scientific Reports"},{"issue":"7","key":"ppat.1014558.ref050","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1128\/IAI.70.7.3673-3680.2002","article-title":"Strain-dependent induction of enterocyte apoptosis by Giardia lamblia disrupts epithelial barrier function in a caspase-3-dependent manner","volume":"70","author":"AC Chin","year":"2002","journal-title":"Infect Immun"},{"issue":"2","key":"ppat.1014558.ref051","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/j.1574-695X.2007.00304.x","article-title":"Caspase-dependent apoptosis of the HCT-8 epithelial cell line induced by the parasite Giardia intestinalis","volume":"51","author":"MA Panaro","year":"2007","journal-title":"FEMS Immunol Med Microbiol"},{"issue":"2","key":"ppat.1014558.ref052","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1645\/GE-3021.1","article-title":"Giardia duodenalis assemblage-specific induction of apoptosis and tight junction disruption in human intestinal epithelial cells: effects of mixed infections","volume":"99","author":"WH Koh","year":"2013","journal-title":"J Parasitol"},{"issue":"3","key":"ppat.1014558.ref053","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1136\/gut.2006.100198","article-title":"Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum","volume":"56","author":"H Troeger","year":"2007","journal-title":"Gut"},{"issue":"1","key":"ppat.1014558.ref054","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1186\/s13071-023-05949-0","article-title":"Giardia VSPAS7 protein attenuates Giardia intestinalis-induced host macrophage pyroptosis","volume":"16","author":"M Sun","year":"2023","journal-title":"Parasit Vectors"},{"issue":"10","key":"ppat.1014558.ref055","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/ni971","article-title":"Mast cell-dependent migration of effector CD8+ T cells through production of leukotriene B4","volume":"4","author":"VL Ott","year":"2003","journal-title":"Nat Immunol"},{"issue":"12","key":"ppat.1014558.ref056","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1084\/jem.20042407","article-title":"Leukotriene B4, an activation product of mast cells, is a chemoattractant for their progenitors","volume":"201","author":"CL Weller","year":"2005","journal-title":"J Exp Med"},{"key":"ppat.1014558.ref057","doi-asserted-by":"crossref","first-page":"104632","DOI":"10.1016\/j.cellimm.2022.104632","article-title":"Leukotriene D4 accelerates antigen-mediated mast cell responses via the cysteinyl leukotriene 1 receptor","volume":"382","author":"S Fujisawa","year":"2022","journal-title":"Cell Immunol"},{"issue":"11","key":"ppat.1014558.ref058","doi-asserted-by":"crossref","first-page":"6642","DOI":"10.1128\/IAI.72.11.6642-6649.2004","article-title":"Mast cell-dependent control of Giardia lamblia infections in mice","volume":"72","author":"E Li","year":"2004","journal-title":"Infect Immun"},{"issue":"7","key":"ppat.1014558.ref059","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1365-3024.2007.00953.x","article-title":"Tumour necrosis factor alpha contributes to protection against Giardia lamblia infection in mice","volume":"29","author":"P Zhou","year":"2007","journal-title":"Parasite Immunol"},{"issue":"9","key":"ppat.1014558.ref060","doi-asserted-by":"crossref","first-page":"4514","DOI":"10.1128\/IAI.00596-07","article-title":"Mast cell-mediated changes in smooth muscle contractility during mouse giardiasis","volume":"75","author":"E Li","year":"2007","journal-title":"Infect Immun"},{"issue":"3","key":"ppat.1014558.ref061","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.exppara.2010.06.013","article-title":"Giardia lamblia: interleukin 6 and tumor necrosis factor-alpha release from mast cells induced through an Ig-independent pathway","volume":"126","author":"S Mu\u00f1oz-Cruz","year":"2010","journal-title":"Exp Parasitol"},{"issue":"4","key":"ppat.1014558.ref062","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1165\/ajrcmb\/7.4.385","article-title":"Human lung mast cells and pulmonary macrophages produce tumor necrosis factor-alpha in sensitized lung tissue after IgE receptor triggering","volume":"7","author":"Y Ohkawara","year":"1992","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"12","key":"ppat.1014558.ref063","doi-asserted-by":"crossref","first-page":"6030","DOI":"10.1128\/IAI.66.12.6030-6034.1998","article-title":"Phagocytic and tumor necrosis factor alpha response of human mast cells following exposure to gram-negative and gram-positive bacteria","volume":"66","author":"M Arock","year":"1998","journal-title":"Infect Immun"},{"issue":"7","key":"ppat.1014558.ref064","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.4049\/jimmunol.151.7.3853","article-title":"Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation","volume":"151","author":"P Bradding","year":"1993","journal-title":"J Immunol"},{"issue":"1","key":"ppat.1014558.ref065","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0008-6363(03)00340-7","article-title":"Stress-induced interleukin-6 release in mice is mast cell-dependent and more pronounced in Apolipoprotein E knockout mice","volume":"59","author":"M Huang","year":"2003","journal-title":"Cardiovasc Res"},{"issue":"11","key":"ppat.1014558.ref066","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.micinf.2016.06.009","article-title":"Adaptive immune response in symptomatic and asymptomatic enteric protozoal infection: evidence for a determining role of parasite genetic heterogeneity in host immunity to human giardiasis","volume":"18","author":"Z Babaei","year":"2016","journal-title":"Microbes Infect"},{"issue":"8","key":"ppat.1014558.ref067","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1038\/s41564-025-02051-2","article-title":"Giardia-induced Type 2 mucosal immunity attenuates intestinal inflammation caused by co-infection or colitis in mice","volume":"10","author":"A Sardinha-Silva","year":"2025","journal-title":"Nat Microbiol"},{"issue":"8","key":"ppat.1014558.ref068","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1007\/s00436-018-5944-1","article-title":"Giardia lamblia: identification of molecules that contribute to direct mast cell activation","volume":"117","author":"S Mu\u00f1oz-Cruz","year":"2018","journal-title":"Parasitol Res"},{"issue":"6","key":"ppat.1014558.ref069","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.4161\/hv.29116","article-title":"Resistance to reinfection in mice as a vaccine model for giardiasis","volume":"10","author":"E Li","year":"2014","journal-title":"Hum Vaccin Immunother"},{"issue":"3","key":"ppat.1014558.ref070","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.exppara.2010.06.014","article-title":"Giardia duodenalis: the double-edged sword of immune responses in giardiasis","volume":"126","author":"S Solaymani-Mohammadi","year":"2010","journal-title":"Exp Parasitol"},{"key":"ppat.1014558.ref071","doi-asserted-by":"crossref","first-page":"817468","DOI":"10.3389\/fimmu.2022.817468","article-title":"Mucosal Defense Against Giardia at the Intestinal Epithelial Cell Interface","volume":"13","author":"S Solaymani-Mohammadi","year":"2022","journal-title":"Front Immunol"},{"issue":"4","key":"ppat.1014558.ref072","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000371","article-title":"Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis","volume":"5","author":"JT Pesce","year":"2009","journal-title":"PLoS Pathog"},{"key":"ppat.1014558.ref073","doi-asserted-by":"crossref","first-page":"102631","DOI":"10.1016\/j.plefa.2024.102631","article-title":"12-Hydroxyeicosatetraenoic acid is the only enzymatically produced HETE increased under brain ischemia","volume":"202","author":"MY Golovko","year":"2024","journal-title":"Prostaglandins Leukot Essent Fatty Acids"},{"issue":"17","key":"ppat.1014558.ref074","doi-asserted-by":"crossref","first-page":"11660","DOI":"10.1074\/jbc.274.17.11660","article-title":"Arachidonic acid is preferentially metabolized by cyclooxygenase-2 to prostacyclin and prostaglandin E2","volume":"274","author":"TG Brock","year":"1999","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1014558.ref075","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12974-020-1703-1","article-title":"Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception","volume":"17","author":"Y Jang","year":"2020","journal-title":"J Neuroinflammation"},{"issue":"5","key":"ppat.1014558.ref076","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.4049\/jimmunol.177.5.3201","article-title":"Leukotrienes are essential for the control of Leishmania amazonensis infection and contribute to strain variation in susceptibility","volume":"177","author":"CH Serezani","year":"2006","journal-title":"J Immunol"},{"issue":"4","key":"ppat.1014558.ref077","doi-asserted-by":"crossref","first-page":"668","DOI":"10.4269\/ajtmh.1999.60.668","article-title":"Role of eicosanoids in the pathogenesis of murine cerebral malaria","volume":"60","author":"L Xiao","year":"1999","journal-title":"Am J Trop Med Hyg"},{"issue":"4","key":"ppat.1014558.ref078","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1086\/381503","article-title":"Cyclooxygenase-2 in the pathogenesis of murine cerebral malaria","volume":"189","author":"HJ Ball","year":"2004","journal-title":"J Infect Dis"},{"issue":"1","key":"ppat.1014558.ref079","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1046\/j.1365-3024.1998.t01-1-00122.x","article-title":"Exogenous cytokines released by spleen and Peyer\u2019s patch cells removed from mice infected with Giardia muris","volume":"20","author":"K Djamiatun","year":"1998","journal-title":"Parasite Immunol"},{"issue":"6","key":"ppat.1014558.ref080","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/ni.2029","article-title":"Regional and mucosal memory T cells","volume":"12","author":"BS Sheridan","year":"2011","journal-title":"Nat Immunol"},{"issue":"10","key":"ppat.1014558.ref081","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nri3738","article-title":"Regional specialization within the intestinal immune system","volume":"14","author":"AM Mowat","year":"2014","journal-title":"Nat Rev Immunol"},{"issue":"9","key":"ppat.1014558.ref082","article-title":"A bacterial bile acid metabolite modulates Treg activity through the nuclear hormone receptor NR4A1","volume":"29","author":"W Li","year":"2021","journal-title":"Cell Host Microbe"},{"issue":"8","key":"ppat.1014558.ref083","doi-asserted-by":"crossref","DOI":"10.1016\/j.chom.2024.06.014","article-title":"A small intestinal bile acid modulates the gut microbiome to improve host metabolic phenotypes following bariatric surgery","volume":"32","author":"Y Chen","year":"2024","journal-title":"Cell Host Microbe"},{"issue":"1","key":"ppat.1014558.ref084","doi-asserted-by":"crossref","first-page":"2172671","DOI":"10.1080\/19490976.2023.2172671","article-title":"Bile acids as modulators of gut microbiota composition and function","volume":"15","author":"AB Larabi","year":"2023","journal-title":"Gut Microbes"},{"issue":"7","key":"ppat.1014558.ref085","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2020.05.036","article-title":"Interpersonal gut microbiome variation drives susceptibility and resistance to cholera infection","volume":"181","author":"S Alavi","year":"2020","journal-title":"Cell"},{"issue":"7533","key":"ppat.1014558.ref086","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nature13828","article-title":"Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile","volume":"517","author":"CG Buffie","year":"2015","journal-title":"Nature"},{"key":"ppat.1014558.ref087","doi-asserted-by":"crossref","first-page":"17562848211017725","DOI":"10.1177\/17562848211017725","article-title":"The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection","volume":"14","author":"BH Mullish","year":"2021","journal-title":"Therap Adv Gastroenterol"},{"issue":"5","key":"ppat.1014558.ref088","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1053\/j.gastro.2011.07.046","article-title":"Bile acid is a host factor that regulates the composition of the cecal microbiota in rats","volume":"141","author":"KBMS Islam","year":"2011","journal-title":"Gastroenterology"},{"issue":"1","key":"ppat.1014558.ref089","doi-asserted-by":"crossref","first-page":"3692","DOI":"10.1038\/s41467-020-17183-8","article-title":"Bile acids drive the newborn\u2019s gut microbiota maturation","volume":"11","author":"N van Best","year":"2020","journal-title":"Nat Commun"},{"issue":"6","key":"ppat.1014558.ref090","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1645\/GE-3497RN.1","article-title":"Reduction in fecal excretion of Giardia cysts: effect of cholestasis and diet","volume":"91","author":"S Erlandsen","year":"2005","journal-title":"J Parasitol"},{"issue":"8","key":"ppat.1014558.ref091","article-title":"Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria","volume":"187","author":"C Li","year":"2024","journal-title":"Cell"},{"issue":"1","key":"ppat.1014558.ref092","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12915-019-0715-8","article-title":"The intestinal microbiota regulates host cholesterol homeostasis","volume":"17","author":"T Le Roy","year":"2019","journal-title":"BMC Biol"},{"key":"ppat.1014558.ref093","doi-asserted-by":"crossref","first-page":"17562848221134396","DOI":"10.1177\/17562848221134396","article-title":"The role of the gut microbiome in colonization resistance and recurrent Clostridioides difficile infection","volume":"15","author":"AM Seekatz","year":"2022","journal-title":"Ther Adv Gastroenterol"},{"issue":"7","key":"ppat.1014558.ref094","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1128\/aem.61.7.2577-2582.1995","article-title":"Purification and Characterization of Conjugated Bile Salt Hydrolase from Bifidobacterium longum BB536","volume":"61","author":"J Grill","year":"1995","journal-title":"Appl Environ Microbiol"},{"issue":"36","key":"ppat.1014558.ref095","doi-asserted-by":"crossref","first-page":"13580","DOI":"10.1073\/pnas.0804437105","article-title":"Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome","volume":"105","author":"BV Jones","year":"2008","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"4","key":"ppat.1014558.ref096","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/0035-9203(83)90120-7","article-title":"Axenic culture of Giardia lamblia in TYI-S-33 medium supplemented with bile","volume":"77","author":"DB Keister","year":"1983","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"4","key":"ppat.1014558.ref097","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/0035-9203(83)90115-3","article-title":"Mammalian bile promotes growth of Giardia lamblia in axenic culture","volume":"77","author":"MJ Farthing","year":"1983","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"3","key":"ppat.1014558.ref098","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/0035-9203(88)90153-8","article-title":"Giardia-bile salt interactions in vitro and in vivo","volume":"82","author":"CE Halliday","year":"1988","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"9","key":"ppat.1014558.ref099","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/0020-7519(95)00029-2","article-title":"Characterization of bile salt uptake by Giardia lamblia","volume":"25","author":"CE Halliday","year":"1995","journal-title":"Int J Parasitol"},{"issue":"2","key":"ppat.1014558.ref100","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/0014-4894(89)90185-9","article-title":"Giardia lamblia: the roles of bile, lactic acid, and pH in the completion of the life cycle in vitro","volume":"69","author":"FD Gillin","year":"1989","journal-title":"Exp Parasitol"},{"issue":"3","key":"ppat.1014558.ref101","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1128\/iai.56.3.705-707.1988","article-title":"Small-intestinal factors promote encystation of Giardia lamblia in vitro","volume":"56","author":"FD Gillin","year":"1988","journal-title":"Infect Immun"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1014558","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014558","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:08:21Z","timestamp":1789150101000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014558"}},"subtitle":[],"editor":[{"given":"William A.","family":"Petri","sequence":"first","affiliation":[{"name":"University of Virginia","place":["UNITED STATES OF AMERICA"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":101,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1014558","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]}}}