{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:06:21Z","timestamp":1784700381295,"version":"3.55.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Hantavirus infection triggers life-threatening hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), driven by severe endothelial barrier breakdown and systemic capillary leakage. Clinical severity varies widely with undefined host regulators, and no targeted endothelial-protective treatments exist. Recent data link hantaviruses to gut microbiome remodeling, while bile acid (BA) receptors FXR and TGR5 potently inhibit NF-\u03baB-mediated endothelial inflammation. We synthesize four core lines of evidence. First, metagenomic reports confirm hantavirus reshapes gut\/lung microbiota in rodent reservoirs. Second, we re-analyzed three public GEO datasets via standardized RNA-seq\/microarray pipelines: (i) GSE245916: SEOV-infected human\/rat lung ECs show conserved VCAM1\/ICAM1 upregulation (human VCAM1 log\n                    <jats:sub>2<\/jats:sub>\n                    FC=+1.17, P\u00a0=\u00a00.023; rat Icam1 log\n                    <jats:sub>2<\/jats:sub>\n                    FC=+0.32, padj=0.016) with unaltered FXR; (ii) GSE7271: SEOV-infected rat lung displays sustained Nfkb1 suppression (all timepoints, P&amp;lt;0.05) and day-15 Slc10a2 downregulation (P\u00a0=\u00a00.028); (iii) GSE270172: PUUV 3D vessel chips feature robust IL6 elevation (log\n                    <jats:sub>2<\/jats:sub>\n                    FC=+1.22, P\u00a0=\u00a03.1\u00d710\n                    <jats:sup>-8<\/jats:sup>\n                    ) and disrupted BA transporters (ABCC3 log\n                    <jats:sub>2<\/jats:sub>\n                    FC=\u22121.44, P\u00a0=\u00a07.4\u00d710\n                    <jats:sup>-<\/jats:sup>\n                    \u00b9\u00b2). TGR5 (GPBAR1) was undetectable in endothelial cells across all datasets. Third, FXR\/TGR5 agonists repress NF-\u03baB inflammation and mitigate lung vascular injury. Fourth, HTNV upregulates CH25H to block HMGCR-dependent cholesterol synthesis, depleting BA precursor substrates. We propose a unified pathogenic model: hantavirus-triggered gut dysbiosis plus virus-impaired cholesterol metabolism deplete circulating FXR\/TGR5 agonistic BAs, relieving constitutive inhibition of endothelial NF-\u03baB and monocyte NLRP3 inflammasomes to exacerbate capillary leakage. We define tiered testable predictions covering clinical multi-omics cohorts,\n                    <jats:italic>in vitro<\/jats:italic>\n                    receptor modulation assays and\n                    <jats:italic>in vivo<\/jats:italic>\n                    pharmacological interventions. This gut microbiota\u2013BA\u2013FXR\/TGR5 axis represents a repurposable therapeutic target for hantavirus diseases, though direct causal evidence connecting BA signaling to viral vascular damage remains absent; our framework offers a rigorous testable roadmap for subsequent validation.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1883162","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:52:09Z","timestamp":1784699529000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bile acid signaling at the gut\u2013vascular interface: a novel modulator of hantavirus endothelial barrier dysfunction"],"prefix":"10.3389","volume":"16","author":[{"given":"Lei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Emergency, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiling","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Emergency, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1016\/j.ccell.2021.03.004","article-title":"Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver","volume":"39","author":"Bertocchi","year":"2021","journal-title":"Cancer Cell."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115900","article-title":"Activation of GPBAR1 attenuates vascular inflammation and atherosclerosis in a mouse model of NAFLD-related cardiovascular disease","volume":"218","author":"Biagioli","year":"2023","journal-title":"Biochem. 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