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We investigated whether AAS promotes IEC death and eosinophilic infiltration under dysbiotic conditions and whether heparin suppresses these effects. Mice pretreated with antibiotics or control water were orally administered AAS. IEC death was assessed by RNA sequencing, western blotting, and flow cytometry. Microbiota composition was analysed by 16S rRNA sequencing, and eosinophilic infiltration was evaluated by histology and flow cytometry. Immortalised murine IECs were stimulated with AAS in the presence or absence of bacterial components, and the effects of heparin were examined in vitro and in vivo. Antibiotic-induced dysbiosis altered IEC metabolic programmes and reduced polysaccharide-degrading bacteria. Under these conditions, AAS further reduced Actinobacteria, including\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    , increased mitochondrial reactive oxygen species (mtROS), and promoted cleavage of caspase-1, caspase-6, caspase-8, caspase-11, interleukin-33, gasdermin D (GSDMD), and gasdermin E (GSDME) in IECs. These changes were associated with epithelial pyroptosis and eosinophilic infiltration in the small intestine. AAS induced similar cleavage events in IECs primed with lipopolysaccharide and lipoteichoic acid in vitro. Antioxidant studies showed that caspase-1\/11-GSDMD activation was ROS-dependent, whereas caspase-6\/8-GSDME activation involved ROS-independent mechanisms. Heparin suppressed these cleavage events, reduced IEC death both in vitro and in vivo, and attenuated eosinophilic inflammation. These findings identify a previously unrecognised pro-inflammatory effect of AAS in the dysbiotic gut and suggest low-dose heparin as a potential protective strategy for intestinal epithelial homoeostasis.\n                  <\/jats:p>","DOI":"10.1038\/s41420-026-03237-1","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:19:08Z","timestamp":1782865148000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Aluminium ammonium sulphate induces epithelial pyroptosis and eosinophilic inflammation under dysbiotic conditions: ameliorative effects of heparin"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9802-5849","authenticated-orcid":false,"given":"Ayako","family":"Wakabayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Owaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4130-2964","authenticated-orcid":false,"given":"Ken","family":"Iwatsuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3091-8686","authenticated-orcid":false,"given":"Etsuko","family":"Toda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0658-7781","authenticated-orcid":false,"given":"Keisuke","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3492-117X","authenticated-orcid":false,"given":"Soichiro","family":"Kumamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3193-6728","authenticated-orcid":false,"given":"Yuichi","family":"Koshiishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1097-9636","authenticated-orcid":false,"given":"Yukino","family":"Machida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2477-8768","authenticated-orcid":false,"given":"Shinobu","family":"Kunugi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9878-5392","authenticated-orcid":false,"given":"Yasuhiro","family":"Nishiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2266-2729","authenticated-orcid":false,"given":"Shoji","family":"Matsune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4974-1574","authenticated-orcid":false,"given":"Yasuyuki","family":"Negishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4485-3609","authenticated-orcid":false,"given":"Rimpei","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"3237_CR1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.jaci.2003.10.047","volume":"113","author":"ME Rothenberg","year":"2004","unstructured":"Rothenberg ME. 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