{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:57:15Z","timestamp":1790787435214,"version":"4.1.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"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. Surg."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hypoganglionosis resembles Hirschsprung disease (HSCR) which is characterized by severe constipation. Enterocolitis due to hypoganglionosis or Hirschsprung-associated enterocolitis (HAEC) is a life-threatening complication of both diseases. This study investigated the role of Paneth-like cells (PLCs) and gut microbiota in the development of enterocolitis in an iatrogenic rectosigmoid hypoganglionosis rat model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The rectosigmoid serosa of male Sprague-Dawley rats were exposed to 0.1% benzalkonium chloride (BAC). The rats were then sacrificed after 1, 3, 5, 8, and 12 weeks. A sham group was sacrificed on Week 12. With hematoxylin-eosin staining, the ganglionic cells were quantified, the degree of enterocolitis was analyzed, and the PLCs was identified. Intestinal barrier function was assessed for the anti-peripherin, occludin, and acetylcholinesterase (AChE)\/butyrylcholinesterase (BChE) ratio. qRT-PCR was used as reference for the evaluation of antimicrobial peptide (AMP) of PLCs using cryptdins, secretory Phospholipase A<jats:sub>2<\/jats:sub>, and lysozyme levels. 16S rRNA high-throughput sequencing on fecal samples was performed to analyze the changes in the intestinal microbiota diversity in each group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After 1 week of intervention, the ganglion cells were fewer in all sacrificial 0.1% BAC groups at varying times than those in the sham group. Occludin and peripherin were decreased, while the AChE\/BChE ratio was increased. At Week 5 postintervention, the number of \u03b1-defensins-positive PLCs increased in the sigmoid colon tissues from BAC-treated rats. Conversely, PLCs-produced AMP decreased from Week 5 to Week 12. The sham group demonstrated increased <jats:italic>Lactobacillus<\/jats:italic> and decreased <jats:italic>Bacteroides<\/jats:italic>, while the 0.1% BAC group exhibited reciprocal changes, indicating dysbiosis. Enterocolitis occurred from Week 1 postintervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Application with BAC influences the disruption of PLCs in Week 5 postintervention, and dysbiosis exacerbate the occurrence of enterocolitis. Further research on Paneth cells involvement in HAEC development is warranted.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fsurg.2024.1407948","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T05:11:27Z","timestamp":1725858687000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Paneth-like cells disruption and intestinal dysbiosis in the development of enterocolitis in an iatrogenic rectosigmoid hypoganglionosis rat model"],"prefix":"10.3389","volume":"11","author":[{"given":"Iskandar Rahardjo","family":"Budianto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kusmardi","family":"Kusmardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andi 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