{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:30:15Z","timestamp":1791822615212,"version":"4.3.4"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"publisher","award":["81901523"],"award-info":[{"award-number":["81901523"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["19ykpy38"],"award-info":[{"award-number":["19ykpy38"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with limited effective treatments. Emerging evidence implicates dysregulation of the microbiota-gut-brain axis in ASD pathogenesis. Oolong tea (OT), a traditional Chinese tea with neuroprotective properties, may modulate this axis, but its effects and mechanisms in ASD remain unclear. We investigated whether OT attenuates neuroinflammation in a valproic acid (VPA)-induced rat model of autism through the microbiota-gut-brain axis and the TLR-4\/I\u03baB-\u03b1\/NF-\u03baB signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An ASD model was established by prenatal VPA exposure (500\u202fmg\/kg, i.p., E12.5). Postnatal VPA-treated rats received OT (100, 200, or 400\u202fmg\/kg\/day) for 4\u202fweeks. Behavioral assessments included self-grooming, marble burying, and three-chamber social interaction tests. Nissl staining evaluated neuropathology. Gut microbiota composition was analyzed using 16S rRNA sequencing of fecal samples. Lipopolysaccharide (LPS), interleukin-6 (IL-6), and tumor necrosis factor-\u03b1 (TNF-\u03b1) levels were measured in the plasma, intestine, and brain using enzyme-linked immunosorbent assay. Intestinal and blood-brain barrier (BBB) integrity (claudin-1\/5, occludin, ZO-1) and TLR-4\/I\u03baB-\u03b1\/NF-\u03baB pathway activation were assessed by Western blot\/immunofluorescence. Microglial (Iba-1) and astrocytic (GFAP) activation and neuronal TLR-4 localization (co-staining with Neun) were examined. Antibiotic cocktail (ABX)-induced microbiota depletion validated gut microbiota dependency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      OT (400\u202fmg\/kg\/day) significantly ameliorated repetitive behaviors (reduced self-grooming duration and marble burying), sociability deficits (improved sociability\/social preference index), and attenuated cortical neuronal loss in VPA-treated rats. OT restored gut microbiota dysbiosis, specifically reducing pathogenic\n                      <jats:italic>Ruminococcaceae<\/jats:italic>\n                      and\n                      <jats:italic>Bacteroides<\/jats:italic>\n                      abundances. It decreased LPS, IL-6, and TNF-\u03b1 levels in the plasma, intestine, and cortex, while enhancing intestinal and BBB tight junction protein expression. OT suppressed TLR-4\/I\u03baB-\u03b1\/NF-\u03baB activation in both intestine and cortex, with TLR-4 predominantly localized to neurons, and reduced microglial\/astrocytic activation. Critically, ABX treatment abolished OT\u2019s neuroprotective effects and restored neuroinflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>OT attenuates ASD-like phenotypes and neuroinflammation in VPA-treated rats by rebalancing gut microbiota, restoring intestinal\/BBB barriers, and inhibiting neuronal TLR-4\/I\u03baB-\u03b1\/NF-\u03baB signaling. This study highlights OT\u2019s potential as a microbiota-targeted therapeutic strategy for ASD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2025.1643147","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T05:27:39Z","timestamp":1757482059000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Oolong tea attenuates neuroinflammation by modulating the microbiota-gut-brain axis in a rat model of 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