Multi-strain probiotic administration decreases necrotizing enterocolitis severity and alters the epigenetic profile in mice.

IF 3.1 3区 医学 Q1 PEDIATRICS Pediatric Research Pub Date : 2024-11-19 DOI:10.1038/s41390-024-03716-0
Daphne H Klerk, Hannah Moore, Daniel J Scheese, Cody Tragesser, Zachariah Raouf, Johannes W Duess, Koichi Tsuboi, Maame E Sampah, Carla M Lopez, Sierra Williams-McLeod, Mahmoud G El Baassiri, Hee-Seong Jang, Thomas Prindle, Sanxia Wang, Menghan Wang, William B Fulton, Chhinder P Sodhi, David J Hackam
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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Impact: 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.

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服用多菌株益生菌可降低小鼠坏死性小肠结肠炎的严重程度并改变表观遗传学特征。
背景:服用益生菌可能会降低坏死性小肠结肠炎(NEC)的发病率,但其机制尚不清楚。我们研究了益生菌对肠道表观遗传学的影响,并使用回肠为主和回肠结肠炎联合小鼠 NEC 模型评估了益生菌对肠道炎症和蠕动的影响:C57BL/6 J小鼠从出生后第3-11天开始灌胃多菌株益生菌,包括婴儿肠杆菌、乳酸杆菌和嗜热菌。小鼠从出生后第 8 天开始接触回肠结肠炎 NEC,其中包括含有 NEC 细菌和 0.5% DSS 的配方奶。使用 Infinium 甲基化测定法测量 DNA 甲基化。通过 70 Kd FITC-右旋糖酐转运时间评估胃肠道蠕动。通过 qPCR 测量喂食益生菌小鼠的益生菌定植情况:结果:服用益生菌可显著改变小肠的表观遗传学特征,降低 NEC 的严重程度,并改善肠道蠕动。益生菌对回肠结肠炎 NEC 模型的影响更为明显: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,增加了对益生菌潜在作用机制的了解,并揭示了使用益生菌后肠粘膜发生的意想不到的表观遗传学改变:这些研究结果阐明了多菌株益生菌在两种与临床相关的 NEC 动物模型中的作用,并进一步揭示了它们的基本作用机制。这项研究为 NEC 的研究提供了一种新的、与临床相关的模型,包括给予 0.5% DSS,以包括该疾病的回肠显性和回肠结肠显性表型。这些结果表明,与临床相关的益生菌菌株能对小鼠的小肠产生表观遗传学效应,并能减轻 NEC 引起的表观遗传学变化。
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来源期刊
Pediatric Research
Pediatric Research 医学-小儿科
CiteScore
6.80
自引率
5.60%
发文量
473
审稿时长
3-8 weeks
期刊介绍: Pediatric Research publishes original papers, invited reviews, and commentaries on the etiologies of children''s diseases and disorders of development, extending from molecular biology to epidemiology. Use of model organisms and in vitro techniques relevant to developmental biology and medicine are acceptable, as are translational human studies
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