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Timosaponin AIII (TAIII), a plant-derived steroidal saponin, effectively inhibits cell proliferation, induces apoptosis, and exhibits anti-inflammatory properties. This study explored the mechanisms of action of TAIII in SS treatment by studying gut microbiota and short-chain fatty acids (SCFAs) using fecal metabolomics.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The model group used non-obese diabetic (NOD) mice. The treatment group was classified into TAIII and hydroxychloroquine groups. The gut microbiota, SCFAs, and metabolites were analyzed using <jats:italic>16S<\/jats:italic> rRNA sequencing, gas chromatography\u2013mass spectrometry analysis, and liquid chromatography\u2013mass spectrometry, respectively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>TAIII effectively alleviated dry mouth in NOD mice, slowed the progression of salivary gland tissue injury, reduced inflammatory factor expression, and increased the levels of aquaporins 1 and 5. TAIII regulated SCFA content and tryptophan metabolism by altering the abundance of the Rikenellaceae_RC9_gut_group, thereby reducing the inflammatory response. TAIII can improve imbalances in the gut microbiota and the metabolic levels of related SCFAs and tryptophan, thereby reducing the level of inflammation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The significant differences observed in the abundance of the Rikenellaceae_RC9_gut_group between the treatment and control groups indicated the potential relationship between bacteria and metabolites in SS.\n<jats:table-wrap>\n                <jats:table>\n                  <jats:tbody>\n                    <jats:tr>\n                      <jats:td colspan=\"2\">\n                        <jats:bold>Key Points<\/jats:bold>\u2022 <jats:italic>The safe and effective treatment of SS with traditional Chinese medicine<\/jats:italic>\u2022 <jats:italic>Multi-means study on intestinal flora, short-chain fatty acids, and metabonomics<\/jats:italic>\n                      <\/jats:td>\n                    <\/jats:tr>\n                  <\/jats:tbody>\n                <\/jats:table>\n              <\/jats:table-wrap>\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s10067-024-07294-8","type":"journal-article","created":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T15:09:10Z","timestamp":1737212950000},"page":"1209-1223","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Fecal metabolomic analysis of the role of gut microbiota and short-chain fatty acids in the therapeutic mechanism of Timosaponin AIII in Sj\u00f6gren\u2019s syndrome"],"prefix":"10.1007","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6981-3240","authenticated-orcid":false,"given":"Fengtao","family":"Pang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopo","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kesong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,18]]},"reference":[{"key":"7294_CR1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s10238-021-00728-6","volume":"22","author":"S Negrini","year":"2022","unstructured":"Negrini S, Emmi G, Greco M et al (2022) Sj\u00f6gren\u2019s syndrome: a systemic autoimmune disease. 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