{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:14:19Z","timestamp":1788430459297,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Taishan Scholar Program of Shandong Province","award":["ts201712087"],"award-info":[{"award-number":["ts201712087"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cigarette smoke exposure is a major preventable risk factor for respiratory disease and drives oxidative and inflammatory lung injury, highlighting the urgent need for safe, multi-target interventions beyond conventional anti-inflammatory therapy. Formononetin (FMN), a naturally occurring isoflavone with antioxidant, anti-inflammatory, and microbiota-modulating potential, may offer a dietary-botanical strategy against smoke-related pulmonary damage. This study evaluated FMN against cigarette smoke extract (CSE)-induced lung injury and explored its associations with intestinal barrier integrity, gut microbiota, taurine metabolism, SLC6A6 expression, and NF-\u03baB activation. In a CSE-challenged mouse model, oral FMN, particularly at 70 mg\/kg, improved body weight gain, reduced the lung index, attenuated pulmonary histopathological injury, restored GSH\/GSSG and SOD, decreased MDA, and suppressed TNF-\u03b1, IL-1\u03b2, and IL-6 expression. FMN also ameliorated colonic injury and restored ZO-1 and occludin expression. Exploratory 16S rRNA sequencing and fecal metabolomics indicated FMN-associated alterations in gut microbial composition and metabolic profiles, with taurine and hypotaurine metabolism identified as a candidate pathway for further investigation. FMN further restored lung taurine content and SLC6A6 expression while inhibiting NF-\u03baB activation. These findings suggest that FMN alleviates CSE-induced lung injury and that this improvement is associated with coordinated changes in gut microbiota composition, taurine metabolism, SLC6A6 expression, and NF-\u03baB activation.<\/jats:p>","DOI":"10.3390\/molecules31173090","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:20:43Z","timestamp":1788427243000},"page":"3090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Formononetin Alleviates Cigarette Smoke Extract-Induced Lung Injury in Mice with Gut Microbiota and Taurine\/SLC6A6\/NF-\u03baB Modulation"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6314-9899","authenticated-orcid":false,"given":"Zheng","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Sen","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2337-9867","authenticated-orcid":false,"given":"Zhongting","family":"Lv","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Shuang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3389-0260","authenticated-orcid":false,"given":"Jia","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6944-2021","authenticated-orcid":false,"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8932-3003","authenticated-orcid":false,"given":"Hui","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0564-4265","authenticated-orcid":false,"given":"Li","family":"Ren","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1016\/S0140-6736(21)01169-7","article-title":"Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990\u20132019: A systematic analysis from the Global Burden of Disease Study 2019","volume":"397","author":"Reitsma","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108365","DOI":"10.1016\/j.mrrev.2021.108365","article-title":"Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer","volume":"787","author":"Caliri","year":"2021","journal-title":"Mutat. 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