{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T12:35:47Z","timestamp":1793709347684,"version":"4.6.1"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T00:00:00Z","timestamp":1793664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T00:00:00Z","timestamp":1793664000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82302408"],"award-info":[{"award-number":["82302408"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Science and Technology Program of Guangzhou City","doi-asserted-by":"publisher","award":["SL2024A04J02216, 2025A04J4752"],"award-info":[{"award-number":["SL2024A04J02216, 2025A04J4752"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,11,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Gut microbiota regulates neuroinflammatory responses involved in the pathogenesis of sepsis-associated encephalopathy (SAE). However, the underlying mechanism remains elusive. 16S rRNA sequencing of fecal samples revealed an expansion of the\n                      <jats:italic toggle=\"yes\">Enterobacteriaceae<\/jats:italic>\n                      family in septic mice, and quantitative PCR further detected an increase in gut\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      . Subsequent bacterial transplantation experiments showed that the exacerbation of neuroinflammatory responses in sepsis by gut microbiota dysbiosis is due to the expansion of gut\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      . Furthermore, we observed an increase in\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      -derived 3-methylindole (3MI) in septic mice. Although 3MI alone does not directly induce neuroinflammation, it synergistically exacerbates neuroinflammatory responses with lipopolysaccharide. Mechanistically, 3MI may reduce the ubiquitination level of NLRP3 and enhance NLRP3 inflammasome activation in lipopolysaccharide-stimulated microglia. These findings suggest that\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      -derived 3MI is a contributing factor in aggravating neuroinflammation in SAE, offering new insights into therapeutic strategies for SAE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The gut-brain axis is increasingly implicated in sepsis\u2011associated encephalopathy (SAE) pathogenesis, yet the precise microbial mechanisms driving neuroinflammation remain poorly defined. This study identifies a specific gut microbial pathway and reveals that sepsis-induced expansion of\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      and its overproduction of the metabolite 3-methylindole are key aggravating factors. Notably, while 3-methylindole alone is non-inflammatory, it acts synergistically with lipopolysaccharide to drive NLRP3 inflammasome activation in microglia, likely via reducing NLRP3 ubiquitination. These findings pinpoint a gut bacterium-derived metabolite as a critical amplifier of brain inflammation in sepsis, which contributes to a new mechanistic understanding of SAE pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01542-26","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:01:06Z","timestamp":1791291666000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Intestinal 3-methylindole exacerbates sepsis-induced neuroinflammation through microglial NLRP3 inflammasome activation"],"prefix":"10.1128","volume":"14","author":[{"given":"Heng","family":"Fang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01vjw4z39","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern 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