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Time\u2010restricted feeding (TRF), which limits daily food intake to specific feeding windows, has been demonstrated to restore microbial balance, enrich SCFA\u2010producing bacteria, and enhance gut homeostasis. Nevertheless, the extent to which TRF confers protection against CD, as well as the mechanisms underlying this effect, remains largely unexplored.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    : Fecal samples were obtained from patients with active CD and from healthy control subjects to quantify the abundance of\n                    <jats:italic>Ruminococcus<\/jats:italic>\n                    . Using 16S rRNA sequencing, we examined the impact of TRF regimens with varying fasting\/feeding cycles (12\/12, 16\/8, and 20\/4) on\n                    <jats:italic>Ruminococcus<\/jats:italic>\n                    . In preclinical CD models, we systematically evaluated the protective effect of TRF by analyzing colonic inflammation and fibrosis using histopathological techniques. RNA\u2010seq and epigenetic analyses were performed to elucidate the underlying mechanisms.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : Fecal\n                    <jats:italic>Ruminococcus<\/jats:italic>\n                    abundance was significantly reduced in patients with CD and inversely correlated with disease activity indices. Among the tested regimens, only the 12\/12 fasting\/feeding regimen (TRF_12h), but not regimens with shorter feeding windows, robustly increased the\n                    <jats:italic>Ruminococcus<\/jats:italic>\n                    abundance and potently stimulated mitochondrial \u03b2\u2010oxidation and lactate generation. Preemptive administration of TRF_12h markedly protected against colitis severity and fibrosis in CD models, as evidenced by marked reductions in F4\/80\n                    <jats:sup>+<\/jats:sup>\n                    \/MPO\n                    <jats:sup>+<\/jats:sup>\n                    inflammatory cell infiltration and decreased extracellular matrix deposition. RNA\u2010seq analysis revealed that TRF\u2010mediated epithelial protection was predominantly driven by SCFA\u2010dependent activation of hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) signaling. IEC\u2010specific knockout of HIF\u20101\u03b1 largely abrogated the protective effects of TRF, confirming its essential role. Mechanistically, TRF\u2010induced gut\u2010derived lactate promoted histone H4K12 lactylation (H4K12la), leading to upregulation of SLC9A3 expression, which reinforced a localized acidic microenvironment conducive to\n                    <jats:italic>Ruminococcus<\/jats:italic>\n                    enrichment.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions<\/jats:bold>\n                    : Collectively, TRF enriches SCFA\u2010producing\n                    <jats:italic>Ruminococcus<\/jats:italic>\n                    through a gut lactate\u2010driven histone lactylation\u2010SLC9A3 signaling axis, thereby alleviating inflammation and fibrosis in Crohn's disease under preventive conditions.\n                    <jats:italic>Rum<\/jats:italic>\n                    inococcus\u2010derived SCFA further enhances epithelial mitochondrial \u03b2\u2010oxidation and activates HIF\u20101\u03b1\u2010dependent signaling pathways to strengthen the barrier integrity. This study provides a compelling mechanistic foundation for the clinical exploration of TRF as a therapeutic dietary strategy for patients with CD.\n                  <\/jats:p>","DOI":"10.1002\/advs.202518419","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T19:49:57Z","timestamp":1775591397000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut Lactate Boosts\n                    <i>Ruminococcus<\/i>\n                    via Histone Lactylation to Mediate Time\u2010Restricted Feeding Protection in Crohn's Disease"],"prefix":"10.1002","volume":"13","author":[{"given":"Linwen","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou 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