{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:15:22Z","timestamp":1788225322773,"version":"build-2803163510"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100014996","name":"Health Commission of Zhejiang Province","doi-asserted-by":"publisher","award":["2023KY197, 2025KY147"],"award-info":[{"award-number":["2023KY197, 2025KY147"]}],"id":[{"id":"10.13039\/501100014996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015807","name":"Hangzhou Municipal Health and Family Planning Commission","doi-asserted-by":"publisher","award":["2025HZGF09"],"award-info":[{"award-number":["2025HZGF09"]}],"id":[{"id":"10.13039\/100015807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,2,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Emerging evidence implicates bile acid-intestinal microbiota interactions in the pathogenesis of pruritus associated with primary biliary cholangitis (PBC). Cholestyramine, a bile acid sequestrant, is clinically recommended for pruritus alleviation. This study investigates its regulatory effects on gut microbiome composition and metabolite profiles. A prospective cohort of 54 pruritic PBC patients and 25 asymptomatic controls underwent longitudinal multi-omics profiling. Fecal 16S rRNA sequencing and untargeted metabolomics were performed pre-\/post-4-week cholestyramine intervention (4 g twice daily). Serum autotaxin, as a biomarker for pruritus assessment, and liver function tests were completed simultaneously. Four important findings were listed as follows. (i) Pruritus phenotype characteristics: Pruritic patients exhibited elevated cholestasis indices (total bilirubin, alkaline phosphatase [ALP], and gamma-glutamyl transferase), higher ATX levels, and increased Gp210 antibody positivity compared to controls (all\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01). Cholestyramine significantly reduced 5-D pruritus scores, ATX levels, and cholestasis markers (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01). (ii) Microbial dysbiosis: Gut microbiota diversity (Shannon\/Simpson indices) was markedly decreased in pruritic patients, with taxonomic enrichment of\n                      <jats:italic toggle=\"yes\">Romboutsia<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Stenotrophomonas<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Achromobacter<\/jats:italic>\n                      , whereas\n                      <jats:italic toggle=\"yes\">Lachnospiraceae<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Bacteroidaceae<\/jats:italic>\n                      predominated in controls. (iii) Metabolomic perturbations: Metabolomic analysis identified diminished medium-chain fatty acids and indole derivatives (e.g., norharman) in pruritic patients. (iv) Therapeutic efficacy: Microbial-metabolite-clinical correlations revealed the pivotal role of the\n                      <jats:italic toggle=\"yes\">Romboutsia<\/jats:italic>\n                      -norharman-ATX\/ALP axis in the pathogenesis of pruritic PBC. Post-treatment, cholestyramine restored microbial diversity, normalized metabolite levels, and attenuated pruritus.\n                      <jats:italic toggle=\"yes\">Enterobacteriaceae<\/jats:italic>\n                      \/long-chain fatty acids have been identified as a significant marker for predicting the efficiency of the response to cholestyramine.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Pruritus in primary biliary cholangitis arises from synergistic cholestasis and gut microbiome-metabolite dysregulation. Cholestyramine mitigates symptoms by modulating the microbiome-metabolite-host axis, highlighting its therapeutic potential through microbiota remodeling and metabolic homeostasis restoration.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00747-25","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T14:00:13Z","timestamp":1767621613000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Variation in microbiome and metabolites is associated with advantageous effects of cholestyramine on primary biliary cholangitis with pruritus"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8607-4999","authenticated-orcid":true,"given":"Yijun","family":"Zhou","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zkkh342","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Hepatology, Hangzhou Xixi Hospital affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoxiang","family":"Ying","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zkkh342","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Hepatology, Hangzhou Xixi Hospital affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zkkh342","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Hepatology, Hangzhou Xixi Hospital affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusheng","family":"Cui","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zkkh342","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Hepatology, Hangzhou Xixi Hospital affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Xiang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zkkh342","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Hepatology, Hangzhou Xixi Hospital affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muyuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Zhejiang Province Hospital of Integrated Traditional Chinese and Western Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Bao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zkkh342","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Hepatology, Hangzhou Xixi Hospital affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8738-8982","authenticated-orcid":true,"given":"Qiaofei","family":"Jin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zkkh342","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Hepatology, Hangzhou Xixi Hospital affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01303-5"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.14218\/JCTH.2020.00119"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00687-7"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1126117"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-024-00830-x"},{"key":"e_1_3_5_7_2","first-page":"1024","article-title":"Guidelines on the diagnosis and management of primary biliary cholangitis (2021)","volume":"60","author":"Chinese Society of Hepatology","year":"2021","unstructured":"Chinese Society of Hepatology, Chinese Medical Association. 2021. 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