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应激诱导的肠易激综合征大鼠模型中结肠微生物群的结构和功能改变

Structural and functional alterations in the colonic microbiome of the rat in a model of stress induced irritable bowel syndrome.

作者信息

Fourie Nicolaas H, Wang Dan, Abey Sarah K, Creekmore Amy L, Hong Shuangsong, Martin Christiana G, Wiley John W, Henderson Wendy A

机构信息

a National Institutes of Health, Division of Intramural Research, NINR, DHHS , Bethesda , MD , USA.

b University of Michigan Medical School , Department of Internal Medicine - Gastroenterology , Ann Arbor , MI , USA.

出版信息

Gut Microbes. 2017 Jan 2;8(1):33-45. doi: 10.1080/19490976.2016.1273999. Epub 2017 Jan 6.

Abstract

Stress is known to perturb the microbiome and exacerbate irritable bowel syndrome (IBS) associated symptoms. Characterizing structural and functional changes in the microbiome is necessary to understand how alterations affect the biomolecular environment of the gut in IBS. Repeated water avoidance (WA) stress was used to induce IBS-like symptoms in rats. The colon-mucosa associated microbiome was characterized in 13 stressed and control animals by 16S sequencing. In silico analysis of the functional domains of microbial communities was done by inferring metagenomic profiles from 16S data. Microbial communities and functional profiles were compared between conditions. WA animals exhibited higher α-diversity and moderate divergence in community structure (β-diversity) compared with controls. Specific clades and taxa were consistently and significantly modified in the WA animals. The WA microbiome was particularly enriched in Proteobacteria and depleted in several beneficial taxa. A decreased capacity in metabolic domains, including energy- and lipid-metabolism, and an increased capacity for fatty acid and sulfur metabolism was inferred for the WA microbiome. The stressed condition favored the proliferation of a greater diversity of microbes that appear to be functionally similar, resulting in a functionally poorer microbiome with implications for epithelial health. Taxa, with known beneficial effects, were found to be depleted, which supports their relevance as therapeutic agents to restore microbial health. Microbial sulfur metabolism may form a key component of visceral nerve sensitization pathways and is therefore of interest as a target metabolic domain in microbial ecological restoration.

摘要

已知压力会扰乱微生物群并加剧肠易激综合征(IBS)相关症状。了解微生物群的结构和功能变化对于理解这些改变如何影响IBS患者肠道的生物分子环境至关重要。采用反复禁水(WA)应激诱导大鼠出现IBS样症状。通过16S测序对13只应激动物和对照动物的结肠黏膜相关微生物群进行了表征。通过从16S数据推断宏基因组图谱,对微生物群落的功能域进行了计算机分析。比较了不同条件下的微生物群落和功能图谱。与对照组相比,WA动物表现出更高的α多样性和群落结构的中度差异(β多样性)。WA动物中特定的进化枝和分类群持续且显著改变。WA微生物群中变形菌门特别丰富,而几种有益分类群减少。推断WA微生物群在包括能量和脂质代谢在内的代谢域中的能力下降,而脂肪酸和硫代谢能力增加。应激条件有利于功能相似的更多样化微生物的增殖,导致功能较差的微生物群,对上皮健康产生影响。发现具有已知有益作用的分类群减少,这支持了它们作为恢复微生物健康的治疗剂的相关性。微生物硫代谢可能构成内脏神经致敏途径的关键组成部分,因此作为微生物生态恢复中的目标代谢域受到关注。

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