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新生儿坏死性小肠结肠炎:发酵代谢与肠致病性。

Neonatal necrotizing enterocolitis: and fermentation metabolism and enteropathogenicity.

机构信息

Université Paris Cité, INSERM, UMR-S 1139, 3PHM, Paris, France.

FHU PREMA « Fighting prematurity, Paris, France.

出版信息

Gut Microbes. 2023 Jan-Dec;15(1):2172666. doi: 10.1080/19490976.2023.2172666.

DOI:10.1080/19490976.2023.2172666
PMID:36801067
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9980464/
Abstract

Bacterial colonization in the gut plays a pivotal role in neonatal necrotizing enterocolitis (NEC) development, but the relationship between bacteria and NEC remains unclear. In this study, we aimed to elucidate whether bacterial butyrate end-fermentation metabolites participate in the development of NEC lesions and confirm the enteropathogenicity of and in NEC. First, we produced and strains impaired in butyrate production by genetically inactivating the gene encoding β-hydroxybutyryl-CoA dehydrogenase that produces end-fermentation metabolites. Second, we evaluated the enteropathogenicty of the hbd-knockout strains in a gnotobiotic quail model of NEC. The analyses showed that animals harboring these strains had significantly fewer and less intense intestinal lesions than those harboring the respective wild-type strains. In the absence of specific biological markers of NEC, the data provide original and new mechanistic insights into the disease pathophysiology, a necessary step for developing potential novel therapies.

摘要

肠道细菌定植在新生儿坏死性小肠结肠炎(NEC)的发展中起着关键作用,但细菌与 NEC 之间的关系仍不清楚。在本研究中,我们旨在阐明丁酸末端发酵代谢产物是否参与 NEC 病变的发展,并确认 和 在 NEC 中的肠致病性。首先,我们通过遗传失活编码β-羟丁酰辅酶 A 脱氢酶的基因,该基因产生末端发酵代谢产物,从而产生 和 菌株,这些菌株不能产生丁酸。其次,我们在 NEC 的无菌鹌鹑模型中评估了 hbd 敲除菌株的肠致病性。分析表明,携带这些菌株的动物的肠道病变数量明显减少,且病变程度较轻,而携带相应野生型菌株的动物则没有。在缺乏 NEC 特异性生物学标志物的情况下,这些数据为该疾病的病理生理学提供了原创性和新的机制见解,这是开发潜在新疗法的必要步骤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0093/9980464/b3bb1593dbe0/KGMI_A_2172666_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0093/9980464/7884dc859d73/KGMI_A_2172666_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0093/9980464/e3d84f34d97f/KGMI_A_2172666_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0093/9980464/e50151eac13e/KGMI_A_2172666_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0093/9980464/c632259d9e34/KGMI_A_2172666_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0093/9980464/cc43f8a3eb03/KGMI_A_2172666_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0093/9980464/b3bb1593dbe0/KGMI_A_2172666_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0093/9980464/7884dc859d73/KGMI_A_2172666_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0093/9980464/e3d84f34d97f/KGMI_A_2172666_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0093/9980464/e50151eac13e/KGMI_A_2172666_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0093/9980464/c632259d9e34/KGMI_A_2172666_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0093/9980464/cc43f8a3eb03/KGMI_A_2172666_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0093/9980464/b3bb1593dbe0/KGMI_A_2172666_F0007_B.jpg

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