{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:36:23Z","timestamp":1788543383044,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovation Platform (base) and Talent Special Project","award":["20210502005ZP"],"award-info":[{"award-number":["20210502005ZP"]}]},{"name":"Innovation Platform (base) and Talent Special Project","award":["20230204038YY"],"award-info":[{"award-number":["20230204038YY"]}]},{"name":"Innovation Platform (base) and Talent Special Project","award":["202410183309"],"award-info":[{"award-number":["202410183309"]}]},{"name":"Key Research and Development Program of Jilin Province","award":["20210502005ZP"],"award-info":[{"award-number":["20210502005ZP"]}]},{"name":"Key Research and Development Program of Jilin Province","award":["20230204038YY"],"award-info":[{"award-number":["20230204038YY"]}]},{"name":"Key Research and Development Program of Jilin Province","award":["202410183309"],"award-info":[{"award-number":["202410183309"]}]},{"name":"University Student Innovation and Entrepreneurship Training Program","award":["20210502005ZP"],"award-info":[{"award-number":["20210502005ZP"]}]},{"name":"University Student Innovation and Entrepreneurship Training Program","award":["20230204038YY"],"award-info":[{"award-number":["20230204038YY"]}]},{"name":"University Student Innovation and Entrepreneurship Training Program","award":["202410183309"],"award-info":[{"award-number":["202410183309"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Steroid-resistant asthma (SRA), resisting glucocorticoids such as dexamethasone (DEX), is a bottleneck in the treatment of asthma. It is characterized by a predominantly neutrophilic inflammatory subtype and is prone to developing into severe refractory asthma and fatal asthma. Currently, there is a lack of universally effective treatments for SRA. Moreover, since cold stimulation does increase the risk of asthma development and exacerbate asthma symptoms, the treatment of cold-stimulated SRA (CSRA) will face greater challenges. To find effective new methods to ameliorate CSRA, this study established a CSRA mouse model of allergic airway inflammation mimicking human asthma for the first time and evaluated the alleviating effects of 80% ethanol extract of mountain-cultivated ginseng (MCG) based on multi-omics analysis. The results indicate that cold stimulation indeed exacerbated the SRA-related symptoms in mice; the DEX individual treatment did not show a satisfactory effect; while the combination treatment of DEX and MCG could dose-dependently significantly enhance the lung function; reduce neutrophil aggregation; decrease the levels of LPS, IFN-\u03b3, IL-1\u03b2, CXCL8, and IL-17; increase the level of IL-10; alleviate the inflammatory infiltration; and decrease the mucus secretion and the expression of MUC5AC. Moreover, the combination of DEX and high-dose (200 mg\/kg) MCG could significantly increase the levels of tight junction proteins (TJs), regulate the disordered intestinal flora, increase the content of short-chain fatty acids (SCFAs), and regulate the abnormal gene profile and metabolic profile. Multi-omics integrated analysis showed that 7 gut microbes, 34 genes, 6 metabolites, and the involved 15 metabolic\/signaling pathways were closely related to the pharmacological effects of combination therapy. In conclusion, integrated multi-omics profiling highlighted the benefits of MCG for CSRA mice by modulating the interactions of microbiota, genes, and metabolites. MCG shows great potential as a functional food in the adjuvant treatment of CSRA.<\/jats:p>","DOI":"10.3390\/ijms25169110","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T05:16:24Z","timestamp":1724649384000},"page":"9110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Integrated Multi-Omics Analysis Reveals Mountain-Cultivated Ginseng Ameliorates Cold-Stimulated Steroid-Resistant Asthma by Regulating Interactions among Microbiota, Genes, and Metabolites"],"prefix":"10.3390","volume":"25","author":[{"given":"Daohao","family":"Tang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0559-3015","authenticated-orcid":false,"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzhe","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luying","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihan","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoming","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0694-4059","authenticated-orcid":false,"given":"Cuizhu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0871-3454","authenticated-orcid":false,"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4020-879X","authenticated-orcid":false,"given":"Jinping","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1183\/09031936.00138707","article-title":"Global strategy for asthma management and prevention: GINA executive summary","volume":"31","author":"Bateman","year":"2008","journal-title":"Eur. 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