{"title":"Paneth-like cells disruption and intestinal dysbiosis in the development of enterocolitis in an iatrogenic rectosigmoid hypoganglionosis rat model","authors":"Iskandar Rahardjo Budianto, Kusmardi Kusmardi, Andi Muh. Maulana, Somasundaram Arumugam, Rejina Afrin, Vivian Soetikno","doi":"10.3389/fsurg.2024.1407948","DOIUrl":null,"url":null,"abstract":"BackgroundHypoganglionosis 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.MethodsThe 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.ResultsAfter 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 α-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.ConclusionApplication 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.","PeriodicalId":12564,"journal":{"name":"Frontiers in Surgery","volume":"95 1","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Surgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fsurg.2024.1407948","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"SURGERY","Score":null,"Total":0}
引用次数: 0
Abstract
BackgroundHypoganglionosis 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.MethodsThe 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 A2, 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.ResultsAfter 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 α-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 Lactobacillus and decreased Bacteroides, while the 0.1% BAC group exhibited reciprocal changes, indicating dysbiosis. Enterocolitis occurred from Week 1 postintervention.ConclusionApplication 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.
期刊介绍:
Evidence of surgical interventions go back to prehistoric times. Since then, the field of surgery has developed into a complex array of specialties and procedures, particularly with the advent of microsurgery, lasers and minimally invasive techniques. The advanced skills now required from surgeons has led to ever increasing specialization, though these still share important fundamental principles.
Frontiers in Surgery is the umbrella journal representing the publication interests of all surgical specialties. It is divided into several “Specialty Sections” listed below. All these sections have their own Specialty Chief Editor, Editorial Board and homepage, but all articles carry the citation Frontiers in Surgery.
Frontiers in Surgery calls upon medical professionals and scientists from all surgical specialties to publish their experimental and clinical studies in this journal. By assembling all surgical specialties, which nonetheless retain their independence, under the common umbrella of Frontiers in Surgery, a powerful publication venue is created. Since there is often overlap and common ground between the different surgical specialties, assembly of all surgical disciplines into a single journal will foster a collaborative dialogue amongst the surgical community. This means that publications, which are also of interest to other surgical specialties, will reach a wider audience and have greater impact.
The aim of this multidisciplinary journal is to create a discussion and knowledge platform of advances and research findings in surgical practice today to continuously improve clinical management of patients and foster innovation in this field.