{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:12:36Z","timestamp":1786119156943,"version":"build-2736575974"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005151","name":"Chinese Academy of Sciences Key Project","doi-asserted-by":"publisher","award":["XZ202301ZR0016G"],"award-info":[{"award-number":["XZ202301ZR0016G"]}],"id":[{"id":"10.13039\/501100005151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study explored the regulatory effects of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) on the TLR4\/NF-\u03baB pathway and intestinal flora in diarrhea-predominant irritable bowel syndrome (IBS-D).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty-eight Wistar rats were randomized into four groups: model (n\u2009=\u200913), blank control (n\u2009=\u20095), HIF-1\u03b1 upregulation (n\u2009=\u20095), and HIF-1\u03b1 downregulation (n\u2009=\u20095). The IBS-D model group received combined acute and chronic stress stimulation for disease induction. On the basis of identical stress intervention, the HIF\u20111\u03b1 upregulation group was additionally exposed to a hypobaric hypoxic chamber, while the HIF\u20111\u03b1 downregulation group underwent intraperitoneal administration of the HIF\u20111\u03b1 antagonist 2\u2011methoxyestradiol to achieve targeted modulation of HIF\u20111\u03b1 expression.the control group was fed conventionally. Two model rats were euthanized on days 0, 7, 14, 21 to analyze colonic HIF-1\u03b1, TLR4 and NF-\u03baB, and feces from the remaining 5 model rats were gathered on days 0, 7, 14, 21, 28 for 16S rRNA sequencing. Gastrointestinal symptoms, mucosal integrity and molecular expression were assessed after 28 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      An IBS-D model was successfully established. HIF-1\u03b1 expression in the model group increased progressively, while TLR4\/NF-\u03baB levels fluctuated but showed an overall increase. The levels of all three markers were significantly higher than those in the control group(P\u2009&lt;\u20090.05). The HIF-1\u03b1 downregulation group exhibited more severe IBS-D symptoms and higher TLR4\/NF-\u03baB expressions than the upregulation group (P\u2009&lt;\u20090.05). At the genus level, the abundance of\n                      <jats:italic>Lachnospiraceae<\/jats:italic>\n                      NK4A136 decreased, whereas the abundance of the\n                      <jats:italic>Prevotellaceae<\/jats:italic>\n                      NK3B31 group,\n                      <jats:italic>Clostridia<\/jats:italic>\n                      UCG\u2009\u2212\u2009014, UCG\u2009\u2212\u2009005, and\n                      <jats:italic>Prevotellaceae<\/jats:italic>\n                      UCG\u2009\u2212\u2009001 increased (P\u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Under systemic hypobaric hypoxic stress, HIF-1\u03b1 suppresses the TLR4\/NF-\u03baB signaling pathway and alleviates intestinal inflammatory responses. Concurrent intestinal hypoxia and inflammatory injury jointly interfere with normal commensal colonization, accompanied by altered gut microbial composition in IBS-D model rats. Changes in HIF-1\u03b1 levels are biologically correlated with shifts in intestinal microbiota, though direct causal regulation of gut flora by HIF-1\u03b1 remains to be verified in further experiments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0355467","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T17:33:37Z","timestamp":1786037617000},"page":"e0355467","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["HIF-1\u03b1 inhibits the TLR4\/NF-\u03baB signaling pathway and modulates intestinal flora in diarrhea-predominant irritable bowel 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