{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:31:46Z","timestamp":1786516306389,"version":"build-2736575974"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"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. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic fatigue syndrome (CFS) is a disabling multisystem disorder characterized by persistent fatigue, post-exertional malaise, unrefreshing sleep, and neurocognitive and gastrointestinal symptoms. Effective non-pharmacological treatments remain limited. Increasing evidence suggests that CFS involves not only peripheral metabolic and gastrointestinal abnormalities but also central nervous system dysfunction. Altered tryptophan metabolism and gut-brain axis dysfunction may contribute to its pathophysiology. Tuina, a manual therapy used in traditional Chinese medicine, has been hypothesized to influence somatosensory, autonomic, stress-related, and gastrointestinal pathways. However, randomized controlled trials evaluating its clinical effects and exploratory gut-brain correlates in CFS remain scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter, parallel-group, randomized controlled trial will enroll 166 participants with CFS, who will be allocated in a 1:1 ratio to a Tuina group or a standardized usual care group. The Tuina group will receive treatment twice weekly for 8\u202fweeks, whereas the control group will receive standardized usual care consisting of health education and symptom-oriented management. The primary objective is to evaluate the effectiveness of Tuina on fatigue severity, assessed by the change in Fatigue Scale-14 (FS-14) score from baseline to week 8. Secondary outcomes include quality of life, sleep, pain, anxiety, depression, gastrointestinal symptoms, bowel function, and handgrip strength. Exploratory mechanistic outcomes include plasma tryptophan-pathway metabolites, gut microbiota profiling, resting-state functional magnetic resonance imaging, and magnetic resonance spectroscopy. Assessments will be conducted at baseline, weeks 4 and 8, and at 12 and 24\u202fweeks after completion of treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study is designed to evaluate the clinical effects of Tuina in CFS while exploring a biologically informed gut-brain framework involving tryptophan metabolism, gut microbiota, and brain network alterations. To our knowledge, few randomized trials in CFS have prospectively integrated clinical, metabolomic, microbiome, and multimodal neuroimaging measures within a single protocol. The findings may help clarify whether a non-pharmacological intervention can modulate interconnected peripheral and central pathways relevant to fatigue and related symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/itmctr.ccebtcm.org.cn\/mgt\/project\/view\/1990257056896122880<\/jats:ext-link>\n                      , Identifier ITMCTR2025002204.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1859226","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:59:53Z","timestamp":1786514393000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tuina for chronic fatigue syndrome: study protocol for a randomized controlled trial integrating tryptophan metabolism, gut microbiota, and brain network alterations"],"prefix":"10.3389","volume":"20","author":[{"given":"Ming","family":"Jin","sequence":"first","affiliation":[{"name":"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitong","family":"Fang","sequence":"additional","affiliation":[{"name":"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanda","family":"Xu","sequence":"additional","affiliation":[{"name":"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Cao","sequence":"additional","affiliation":[{"name":"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghu","family":"Li","sequence":"additional","affiliation":[{"name":"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ren","sequence":"additional","affiliation":[{"name":"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoujian","family":"Wang","sequence":"additional","affiliation":[{"name":"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjun","family":"Kong","sequence":"additional","affiliation":[{"name":"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]},{"name":"Institute of Tuina, Shanghai Institute of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingguang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Tuina, Shanghai Institute of Traditional Chinese Medicine","place":["Shanghai, China"]},{"name":"Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Fang","sequence":"additional","affiliation":[{"name":"Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]},{"name":"Institute of Tuina, Shanghai Institute of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.mri.2015.12.008","article-title":"Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: an arterial spin-labeling fMRI study","volume":"34","author":"Boissoneault","year":"2016","journal-title":"Magn. 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