{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T06:47:17Z","timestamp":1782715637406,"version":"3.54.5"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the mechanism underlying the association between gut microbiota metabolites and insomnia, focusing on the \u201cgut microbiota-metabolite-target\u201d axis. The Cinnamomi Cortex-Gardeniae Fructus (CC-GF) combination was used as an intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Network pharmacology was applied to predict insomnia-related gut microbiota metabolites and their targets. A PCPA-induced rat insomnia model was established, and gut microbiota dysbiosis was validated using 16S rRNA sequencing. Core gut microbiota were identified, and core targets were screened via protein\u2013protein interaction (PPI) network analysis and multi-algorithm ranking. A \u201ccore microbiota-metabolite-core target\u201d network was constructed, and binding affinities were verified using molecular docking and molecular dynamics simulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty-eight targets were predicted, and CASP3, NFE2L2, HDAC1, and CCND1 were identified as core targets related to oxidative stress, apoptosis, epigenetic regulation, and circadian disturbance. In the insomnia model, the beneficial genera\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      and\n                      <jats:italic>Bacteroides<\/jats:italic>\n                      were decreased, whereas the harmful genera\n                      <jats:italic>Ruminococcus<\/jats:italic>\n                      and\n                      <jats:italic>Blautia<\/jats:italic>\n                      were increased. Nine key metabolites were identified; folic acid exhibited the strongest binding affinity to the core targets (average \u22128.83 kcal\/mol) and was defined as the core metabolite. CC-GF reversed these microbiota alterations, confirming the regulatory role of this axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study elucidates the \u201cgut microbiota-metabolite-target\u201d axis in insomnia and highlights the \u201c\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      -folic acid-target\u201d pathway as a core mechanism. CC-GF intervention provides experimental evidence supporting this axis as a target for insomnia treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1830736","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T06:26:28Z","timestamp":1782714388000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The gut microbiota-metabolite-target axis in insomnia: network pharmacology and gut microbiota profiling insights into pathogenesis and intervention with Cinnamomi Cortex-Gardeniae Fructus"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiaquan","family":"Yuan","sequence":"first","affiliation":[{"name":"Gradute School of Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyang","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyang","family":"Xu","sequence":"additional","affiliation":[{"name":"Gradute School of Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyao","family":"Jiao","sequence":"additional","affiliation":[{"name":"Gradute School of Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Gradute School of Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiucai","family":"Wu","sequence":"additional","affiliation":[{"name":"Gradute School of Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangxi International Zhuang Medicine Hospital","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwei","family":"Hao","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1225403","DOI":"10.3389\/fneur.2023.1225403","article-title":"The association between serum total folic acid concentration and severe difficulty falling asleep in US adults: NHANES 2005-2008","volume":"14","author":"An","year":"2023","journal-title":"Front. 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