Klerk Daphne H, Moore Hannah, Scheese Daniel J, Tragesser Cody, Raouf Zachariah, Duess Johannes W, Tsuboi Koichi, Sampah Maame E, Lopez Carla M, Williams-McLeod Sierra, El Baassiri Mahmoud G, Jang Hee-Seong, Prindle Thomas, Wang Sanxia, Wang Menghan, Fulton William B, Sodhi Chhinder P, Hackam David J
Division of Pediatric Surgery, Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Division of Neonatology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Pediatr Res. 2024 Nov 19. doi: 10.1038/s41390-024-03716-0.
Probiotic administration may decrease the incidence of necrotizing enterocolitis (NEC) through mechanisms that are largely unknown. We investigated the effects of probiotics on intestinal epigenetics and assessed their effects on intestinal inflammation and motility using both ileum-predominant and combined ileo-colitis mouse NEC models.
C57BL/6 J mice were gavage-fed a multi-strain probiotic from postnatal days 3-11, consisting of B. infantis, B. lactis, and S. thermophilus. From p8, mice were exposed to ileo-colitis NEC involving formula containing NEC bacteria and 0.5% DSS. DNA methylation was measured using the Infinium Methylation Assay. Gastrointestinal motility was assessed by 70 Kd FITC-dextran transit time. Probiotic colonization was measured in probiotic-fed mice by qPCR.
Probiotic administration caused significant changes in the small intestine's epigenetic signature, a reduction in NEC severity, and improved intestinal motility. The effects of probiotics were more pronounced in the ileo-colitis NEC model.
These findings shed light on the role of probiotics in two clinically relevant models of NEC, add additional insights into their underlying mechanism of action, and reveal unanticipated epigenetic modifications to the intestinal mucosa after their use.
These findings shed light on the role of multi-strain probiotics in two clinically relevant animal models of NEC, and add additional insights into their underlying mechanism of action This study provides a new, clinically relevant model for the study of NEC including administration of 0.5% DSS, to include ileal dominant and ileo-colonic dominant phenotypes of the disease. These results reveal that clinically relevant strains of probiotic bacteria can exert epigenetic effects on the small intestine in mice, and can attenuate the epigenetic changes induced by NEC.
益生菌给药可能通过很大程度上未知的机制降低坏死性小肠结肠炎（NEC）的发病率。我们研究了益生菌对肠道表观遗传学的影响，并使用以回肠为主和回肠 - 结肠炎联合的小鼠NEC模型评估了它们对肠道炎症和运动的影响。
C57BL/6J小鼠从出生后第3天至11天通过灌胃给予多菌株益生菌，该益生菌由婴儿双歧杆菌、乳酸双歧杆菌和嗜热链球菌组成。从第8天起，小鼠暴露于包含NEC细菌和0.5%葡聚糖硫酸钠（DSS）的配方奶引起的回肠 - 结肠炎NEC模型中。使用Infinium甲基化检测法测量DNA甲基化。通过70Kd异硫氰酸荧光素（FITC） - 葡聚糖转运时间评估胃肠动力。通过定量聚合酶链反应（qPCR）测量给予益生菌小鼠中的益生菌定植情况。
给予益生菌导致小肠表观遗传特征发生显著变化，NEC严重程度降低，肠道运动改善。益生菌的作用在回肠 - 结肠炎NEC模型中更为明显。
这些发现阐明了益生菌在两种临床相关的NEC模型中的作用，为其潜在作用机制提供了更多见解，并揭示了使用益生菌后肠道黏膜意外的表观遗传修饰。
这些发现阐明了多菌株益生菌在两种临床相关的NEC动物模型中的作用，并为其潜在作用机制提供了更多见解。本研究为NEC研究提供了一种新的临床相关模型，包括给予0.5% DSS，涵盖该疾病的回肠为主型和回肠 - 结肠为主型表型。这些结果表明，临床相关的益生菌菌株可对小鼠小肠产生表观遗传效应，并可减弱由NEC诱导的表观遗传变化。
