{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:02:53Z","timestamp":1784872973709,"version":"3.55.0"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"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. Cell. Neurosci."],"abstract":"<jats:p>Secondary neuroinflammation after spinal cord injury (SCI) is a key pathological process that affects neuronal survival, axonal regeneration, and functional recovery. Increasing evidence suggests that dysbiosis of the gut microbiota, disruption of the intestinal barrier, and abnormal microbial inflammatory and metabolic signals may promote the progression of secondary injury after SCI. However, direct, continuous, and cell-type-specific evidence explaining how gut-derived signals influence glial and neurovascular unit responses within the injured spinal cord through peripheral immune imbalance, blood-spinal cord barrier (BSCB) disruption, and local molecular pathways remains limited. In this narrative review, we organize the existing literature into an evidence map and propose a mechanistic hypothesis: After SCI, autonomic dysfunction, impaired gut motility, and neurogenic bowel dysfunction may disrupt the homeostasis of gut microbiota and barrier, leading to lipopolysaccharide (LPS) overflow, reduced short-chain fatty acids (SCFAs), altered tryptophan metabolism, and increased trimethylamine N-oxide (TMAO). These signals may modulate the responses of microglia\/infiltrating macrophages, astrocytes, and the neurovascular unit via peripheral immunity, BSCB, and pathways, including TLR4\/NF-\u03baB, NLRP3, and AhR. We also distinguish direct SCI evidence, single-study support, and extrapolated evidence, and specifically avoid presenting the tryptophan metabolite-AhR axis or TMAO-NLRP3 axis as established SCI pathways. Overall, the gut-spinal cord axis may provide a useful framework for understanding and targeting secondary neuroinflammation after SCI. Still, its causal chain, temporal characteristics, and cell-specific effects require further validation.<\/jats:p>","DOI":"10.3389\/fncel.2026.1897379","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:35:36Z","timestamp":1784871336000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut-derived signals regulating glial activation and secondary neuroinflammation after spinal cord injury: an evidence mapping and mechanistic framework"],"prefix":"10.3389","volume":"20","author":[{"given":"Baoxiu","family":"Yi","sequence":"first","affiliation":[{"name":"College of Clinical Medicine, Jiangxi University of Traditional Chinese Medicine","place":["Nanchang, Jiangxi, China"]},{"name":"The Affiliated Hospital of Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenguang","family":"Chen","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhai","family":"Chi","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangjian","family":"Mao","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelai","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangxi Hospital Affiliated to Longhua Hospital, Shanghai University of Traditional Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13070581","article-title":"NF-\u03baB and JAK\/STAT signaling pathways as crucial regulators of neuroinflammation and astrocyte modulation in spinal cord injury","volume":"13","author":"Ageeva","year":"2024","journal-title":"Cells"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut microbiota regulation of tryptophan metabolism in health and disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"17018","DOI":"10.1038\/nrdp.2017.18","article-title":"Traumatic spinal cord injury","volume":"3","author":"Ahuja","year":"2017","journal-title":"Nat. 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