Paneth-like cells disruption and intestinal dysbiosis in the development of enterocolitis in an iatrogenic rectosigmoid hypoganglionosis rat model

IF 1.6 4区医学 Q2 SURGERY Frontiers in Surgery Pub Date : 2024-09-09 DOI:10.3389/fsurg.2024.1407948

Iskandar Rahardjo Budianto, Kusmardi Kusmardi, Andi Muh. Maulana, Somasundaram Arumugam, Rejina Afrin, Vivian Soetikno

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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.

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类盘状细胞破坏和肠道菌群失调在先天性直肠乙状结肠发育不全大鼠肠炎发病过程中的作用

背景扁桃体功能减退症（Hypoganglionosis）与以严重便秘为特征的赫氏病（Hirschsprung disease，HSCR）相似。低位小肠结肠症引起的小肠结肠炎或赫氏相关性小肠结肠炎（HAEC）是这两种疾病的一种危及生命的并发症。本研究探讨了类潘氏细胞（PLCs）和肠道微生物群在先天性直肠乙状结肠下垂症大鼠模型中肠结肠炎发生过程中的作用。方法将雄性 Sprague-Dawley 大鼠的直肠乙状结肠浆膜暴露于 0.1% 的苯扎氯铵（BAC）中。大鼠分别在 1、3、5、8 和 12 周后被处死。假组在第 12 周牺牲。通过苏木精-伊红染色，对神经节细胞进行量化，分析肠炎的程度，并确定 PLC。利用隐球蛋白、分泌型磷脂酶 A2 和溶菌酶水平的 qRT-PCR 作为参考，评估 PLC 的抗菌肽 (AMP)。对粪便样本进行了 16S rRNA 高通量测序，以分析各组肠道微生物群多样性的变化。闭锁素和外周素减少，而 AChE/BChE 比率增加。干预后第 5 周，BAC 处理大鼠乙状结肠组织中的α-防御素阳性 PLC 数量增加。相反，从第 5 周到第 12 周，PLCs 产生的 AMP 有所减少。假结肠组显示乳酸杆菌增加，而嗜酸乳杆菌减少，而 0.1% BAC 组则显示出相反的变化，表明菌群失调。结论应用 BAC 会影响干预后第 5 周 PLC 的破坏，而菌群失调会加剧肠炎的发生。有必要对 Paneth 细胞参与 HAEC 发育的情况进行进一步研究。

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来源期刊

Frontiers in Surgery Medicine-Surgery

CiteScore

1.90

自引率

11.10%

发文量

1872

审稿时长

12 weeks

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.