{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T16:00:18Z","timestamp":1785513618653,"version":"3.56.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The gut\u2013skin axis is increasingly implicated in atopic dermatitis (AD), but randomized adult studies linking clinical response to paired gut microbiome and circulating metabolite profiling remain limited. We evaluated Qing-Re-Qu-Shi formula in adults with moderate AD and examined associated microbiome and serum metabolite changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this randomized, double-blind, placebo-controlled 12-week trial, 152 adults with moderate AD were assigned 1:1 to Qing-Re-Qu-Shi formula or placebo. Outcomes included Eczema Area and Severity Index (EASI), SCORAD, Patient-Oriented Eczema Measure (POEM), pruritus numerical rating scale (NRS), Dermatology Life Quality Index (DLQI), and responder rates. The primary clinical analysis followed the intention-to-treat principle. Paired fecal 16S rRNA sequencing and targeted serum metabolomics were performed in the biospecimen subset. Differential feature analyses adjusted for baseline level, age, and sex;\n                      <jats:italic>\u03b2<\/jats:italic>\n                      diversity was assessed using repeated-measures-aware PERMANOVA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All randomized participants were included in clinical analyses; 124 contributed paired fecal and serum specimens, and 102 also had week-12 clinical data for cross-domain analyses. Compared with placebo, Qing-Re-Qu-Shi produced greater week-12 improvements in EASI (adjusted mean difference, \u22123.78; 95% CI, \u22124.54 to \u22123.01), SCORAD (\u22129.73; 95% CI, \u221211.54 to \u22127.93), POEM (\u22123.39; 95% CI, \u22124.06 to \u22122.73), pruritus NRS (\u22120.94; 95% CI, \u22121.15 to \u22120.72), and DLQI (\u22122.86; 95% CI, \u22123.47 to \u22122.26) (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). EASI-50 and EASI-75 responses were more frequent with Qing-Re-Qu-Shi. Shannon diversity changed little, whereas\n                      <jats:italic>\u03b2<\/jats:italic>\n                      diversity showed a small but significant group-by-time effect (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.001,\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f0.016). Full-feature CLR analyses identified higher Blautia, Bifidobacterium, Lactobacillus, and Agathobacter and lower Escherichia\/Shigella, Enterococcus, Prevotella, and Collinsella after false-discovery-rate correction. Serum metabolomics showed higher short-chain fatty acid and indole-related signals and lower kynurenine-related signals. Cross-domain correlations aligned these changes with greater symptom improvement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Qing-Re-Qu-Shi formula improved clinical severity and patient-reported outcomes in adults with moderate AD. These benefits were accompanied by selective gut microbial remodeling and circulating microbiota-related metabolite changes, supporting an associative link between clinical improvement and gut ecosystem remodeling rather than proving causality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1847003","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:14:11Z","timestamp":1785510851000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Qing-Re-Qu-Shi formula improves clinical outcomes and is accompanied by gut microbiota and microbial metabolite remodeling in adults with moderate atopic dermatitis: a randomized placebo-controlled multi-omics trial"],"prefix":"10.3389","volume":"13","author":[{"given":"Yi","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology, Anting Hospital of Jiading District","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Anting Hospital of Jiading District","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Anting Hospital of Jiading District","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuli","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Anting Hospital of Jiading District","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Anting Hospital of Jiading District","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1093\/bjd\/ljad339","article-title":"Global epidemiology of atopic dermatitis: a comprehensive systematic analysis and modelling study","volume":"190","author":"Tian","year":"2023","journal-title":"Br J 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