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肠易激综合征患者粪便白色假丝酵母菌的遗传和表型多样性。

Genetic and phenotypic diversity of fecal Candida albicans strains in irritable bowel syndrome.

机构信息

Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.

Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.

出版信息

Sci Rep. 2022 Mar 30;12(1):5391. doi: 10.1038/s41598-022-09436-x.

DOI:10.1038/s41598-022-09436-x
PMID:35354908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8967921/
Abstract

Irritable bowel syndrome (IBS) is a common disorder characterized by chronic abdominal pain and changes in bowel movements. Visceral hypersensitivity is thought to be responsible for pain complaints in a subset of patients. In an IBS-like animal model, visceral hypersensitivity was triggered by intestinal fungi, and lower mycobiota α-diversity in IBS patients was accompanied by a shift toward increased presence of Candida albicans and Saccharomyces cerevisiae. Yet, this shift was observed in hypersensitive as well as normosensitive patients and diversity did not differ between IBS subgroups. The latter suggests that, when a patient changes from hyper- to normosensitivity, the relevance of intestinal fungi is not necessarily reflected in compositional mycobiota changes. We now confirmed this notion by performing ITS1 sequencing on an existing longitudinal set of fecal samples. Since ITS1 methodology does not recognize variations within species, we next focused on heterogeneity within cultured healthy volunteer and IBS-derived C. albicans strains. We observed inter- and intra-individual genomic variation and partial clustering of strains from hypersensitive patients. Phenotyping showed differences related to growth, yeast-to-hyphae morphogenesis and gene expression, specifically of the gene encoding fungal toxin candidalysin. Our investigations emphasize the need for strain-specific cause-and-effect studies within the realm of IBS research.

摘要

肠易激综合征(IBS)是一种常见的疾病,其特征为慢性腹痛和肠道运动的改变。内脏高敏感被认为是部分患者出现疼痛症状的原因。在类似 IBS 的动物模型中,内脏高敏感是由肠道真菌引发的,而 IBS 患者的微生物 α 多样性较低,同时伴随着白色念珠菌和酿酒酵母的增加。然而,这种变化不仅在高敏感患者中观察到,在正常敏感患者中也观察到,而且 IBS 亚组之间的多样性没有差异。这表明,当患者从高敏感转变为正常敏感时,肠道真菌的相关性不一定反映在微生物群落的组成变化中。我们现在通过对现有的粪便样本纵向集进行 ITS1 测序,证实了这一观点。由于 ITS1 方法不能识别物种内的变异,因此我们接下来专注于培养的健康志愿者和 IBS 来源的白色念珠菌菌株内的异质性。我们观察到来自高敏感患者的菌株存在个体间和个体内的基因组变异和部分聚类。表型分析显示与生长、酵母到菌丝形态发生和基因表达相关的差异,特别是与真菌毒素 candidalysin 编码基因相关的差异。我们的研究强调了在 IBS 研究领域中进行基于菌株的因果关系研究的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1c5/8967921/d5682ec21317/41598_2022_9436_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1c5/8967921/f7e0775b8455/41598_2022_9436_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1c5/8967921/237a392f3ac0/41598_2022_9436_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1c5/8967921/e2e2044b1477/41598_2022_9436_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1c5/8967921/d5682ec21317/41598_2022_9436_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1c5/8967921/f7e0775b8455/41598_2022_9436_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1c5/8967921/237a392f3ac0/41598_2022_9436_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1c5/8967921/e2e2044b1477/41598_2022_9436_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1c5/8967921/d5682ec21317/41598_2022_9436_Fig4_HTML.jpg

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