Protection against experimental necrotizing enterocolitis by fecal filtrate transfer requires an active donor virome.

IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-04-10 DOI:10.1080/19490976.2025.2486517
Malene Roed Spiegelhauer, Simone Margaard Offersen, Xiaotian Mao, Michela Gambino, Dennis Sandris Nielsen, Duc Ninh Nguyen, Anders Brunse
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引用次数: 0

Abstract

Necrotizing enterocolitis (NEC) remains a frequent catastrophic disease in preterm infants, and fecal filtrate transfer (FFT) has emerged as a promising prophylactic therapy. This study explored the role of virome viability for the protective effect of FFT. Using ultraviolet (UV) irradiation, we established a viral inactivation protocol and administered FFT, UV-inactivated FFT (iFFT) or sterile saline orally to preterm piglets at risk for experimental NEC. The gut pathology and barrier properties were assessed, while the microbiome was explored by 16S rRNA amplicon and metavirome sequencing. Like in prior studies, FFT reduced NEC severity and intestinal inflammation, while these effects were absent in the iFFT group. Unexpectedly, piglets receiving FFT exhibited mild side effects in the form of early-onset diarrhea. The FFT also converged the gut colonization by increased viral heterogeneity and a reduced abundance of pathobionts like Clostridium perfringens and Escherichia. In contrast, the gut microbiome of iFFT recipients diverged from both FFT and the controls. These findings highlight the clear distinction between the ability of active and inactivate viromes to modulate gut microbiota and decrease pathology. The efficacy of FFT may be driven by active bacteriophages, and loss of virome activity could have consequences for the treatment efficacy.

通过粪便滤液转移对实验性坏死性小肠结肠炎的保护需要一个活跃的供体病毒。
坏死性小肠结肠炎(NEC)仍然是早产儿常见的灾难性疾病,粪便滤液转移(FFT)已成为一种有希望的预防治疗方法。本研究探讨了病毒活力在FFT保护作用中的作用。我们利用紫外线(UV)照射建立了一种病毒灭活方案,并对有实验性NEC风险的早产仔猪口服FFT、UV灭活FFT或无菌生理盐水。评估肠道病理和屏障特性,同时通过16S rRNA扩增子和元病毒组测序探索微生物组。与先前的研究一样,FFT降低了NEC的严重程度和肠道炎症,而这些作用在iFFT组中不存在。出乎意料的是,接受FFT的仔猪表现出轻微的副作用,表现为早发性腹泻。FFT还通过增加病毒异质性和减少产气荚膜梭菌和埃希氏菌等病原体的丰度来聚集肠道定植。相比之下,iFFT接受者的肠道微生物组与FFT和对照组都存在差异。这些发现强调了活性和灭活病毒组调节肠道微生物群和减少病理的能力之间的明显区别。FFT的效果可能是由活性噬菌体驱动的,而病毒活性的丧失可能会对治疗效果产生影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Gut Microbes
Gut Microbes Medicine-Microbiology (medical)
CiteScore
18.20
自引率
3.30%
发文量
196
审稿时长
10 weeks
期刊介绍: The intestinal microbiota plays a crucial role in human physiology, influencing various aspects of health and disease such as nutrition, obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and more. Gut Microbes serves as a platform for showcasing and discussing state-of-the-art research related to the microorganisms present in the intestine. The journal emphasizes mechanistic and cause-and-effect studies. Additionally, it has a counterpart, Gut Microbes Reports, which places a greater focus on emerging topics and comparative and incremental studies.
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