High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation.

IF 12.2 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-04-27 DOI:10.1080/19490976.2025.2489071

Jelle Slager, Hanna L Simpson, Ranko Gacesa, Lianmin Chen, Ineke L Tan, Jody Gelderloos, Astrid Maatman, Cisca Wijmenga, Alexandra Zhernakova, Jingyuan Fu, Rinse K Weersma, Gieneke Gonera, Iris H Jonkers, Sebo Withoff

{"title":"High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation.","authors":"Jelle Slager, Hanna L Simpson, Ranko Gacesa, Lianmin Chen, Ineke L Tan, Jody Gelderloos, Astrid Maatman, Cisca Wijmenga, Alexandra Zhernakova, Jingyuan Fu, Rinse K Weersma, Gieneke Gonera, Iris H Jonkers, Sebo Withoff","doi":"10.1080/19490976.2025.2489071","DOIUrl":null,"url":null,"abstract":"Background: Coeliac disease (CeD) is an immune-mediated disorder primarily affecting the small intestine, characterized by an inflammatory immune reaction to dietary gluten. CeD onset results from a multifaceted interplay of genetic and environmental factors. While recent data show that alterations in gut microbiome composition could play an important role, many current studies are constrained by small sample sizes and limited resolution.Methods: To address these limitations, we analyzed fecal gut microbiota from two Dutch cohorts, CeDNN (128 treated CeD patients (tCeD), 106 controls) and the Lifelines Dutch Microbiome Project (24 self-reported tCeD, 654 controls), using shotgun metagenomic sequencing. Self-reported IBS (570 cases, 1710 controls) and IBD (93 cases, 465 controls) were used as comparative conditions of the gastrointestinal tract. Interindividual variation within the case and control groups was calculated at whole microbiome and strain level. Finally, species-specific gene repertoires were analyzed in tCeD patients and controls.Results: Within-individual microbiome diversity was decreased in patients with self-reported IBS and IBD but not in tCeD patients. Each condition displayed a unique microbial pattern and, in addition to confirming previously reported microbiome associations, we identify an increase in the levels of Clostridium sp. CAG:253, Roseburia hominis, and Eggerthella lenta, amongst others. We further show that the observed changes can partially be explained by gluten-free diet adherence. We also observe increased interindividual variation of gut microbiome composition among tCeD patients and a higher bacterial mutation frequency in tCeD that contributes to higher interindividual variation at strain level. In addition, the immotile European subspecies of Eubacterium rectale, which has a distinct carbohydrate metabolism potential, was nearly absent in tCeD patients.Conclusion: Our study sheds light on the complex interplay between the gut microbiome and CeD, revealing increased interindividual variation and strain-level variation in tCeD patients. These findings expand our understanding of the microbiome's role in intestinal health and disease.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2489071"},"PeriodicalIF":12.2000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036492/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gut Microbes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/19490976.2025.2489071","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/27 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Coeliac disease (CeD) is an immune-mediated disorder primarily affecting the small intestine, characterized by an inflammatory immune reaction to dietary gluten. CeD onset results from a multifaceted interplay of genetic and environmental factors. While recent data show that alterations in gut microbiome composition could play an important role, many current studies are constrained by small sample sizes and limited resolution.

Methods: To address these limitations, we analyzed fecal gut microbiota from two Dutch cohorts, CeDNN (128 treated CeD patients (tCeD), 106 controls) and the Lifelines Dutch Microbiome Project (24 self-reported tCeD, 654 controls), using shotgun metagenomic sequencing. Self-reported IBS (570 cases, 1710 controls) and IBD (93 cases, 465 controls) were used as comparative conditions of the gastrointestinal tract. Interindividual variation within the case and control groups was calculated at whole microbiome and strain level. Finally, species-specific gene repertoires were analyzed in tCeD patients and controls.

Results: Within-individual microbiome diversity was decreased in patients with self-reported IBS and IBD but not in tCeD patients. Each condition displayed a unique microbial pattern and, in addition to confirming previously reported microbiome associations, we identify an increase in the levels of Clostridium sp. CAG:253, Roseburia hominis, and Eggerthella lenta, amongst others. We further show that the observed changes can partially be explained by gluten-free diet adherence. We also observe increased interindividual variation of gut microbiome composition among tCeD patients and a higher bacterial mutation frequency in tCeD that contributes to higher interindividual variation at strain level. In addition, the immotile European subspecies of Eubacterium rectale, which has a distinct carbohydrate metabolism potential, was nearly absent in tCeD patients.

Conclusion: Our study sheds light on the complex interplay between the gut microbiome and CeD, revealing increased interindividual variation and strain-level variation in tCeD patients. These findings expand our understanding of the microbiome's role in intestinal health and disease.

查看原文本刊更多论文

经治疗的乳糜泻微生物组的高分辨率分析揭示了菌株水平的变化。

背景：乳糜泻（CeD）是一种免疫介导的疾病，主要影响小肠，其特征是对饮食面筋的炎症免疫反应。CeD的发病是遗传和环境因素多方面相互作用的结果。虽然最近的数据显示肠道微生物组组成的改变可能发挥重要作用，但目前许多研究受到小样本量和有限分辨率的限制。方法：为了解决这些局限性，我们使用鸟枪宏基因组测序分析了来自两个荷兰队列的粪便肠道微生物群，CeDNN（128名接受治疗的CeD患者（tCeD）， 106名对照）和生命线荷兰微生物组项目（24名自我报告的tCeD， 654名对照）。以自我报告的IBS（570例，1710例对照）和IBD（93例，465例对照）作为胃肠道比较条件。在整个微生物组和菌株水平上计算病例组和对照组的个体间变异。最后，分析了tCeD患者和对照组的物种特异性基因库。结果：在自我报告的IBS和IBD患者中，个体内微生物组多样性降低，但在tCeD患者中没有。每种情况都显示出独特的微生物模式，除了证实先前报道的微生物组关联外，我们还发现梭状芽孢杆菌CAG:253，人玫瑰属和长绒蛋杆菌等水平增加。我们进一步表明，观察到的变化可以部分解释无谷蛋白饮食的坚持。我们还观察到tCeD患者肠道微生物组组成的个体间差异增加，tCeD患者的细菌突变频率更高，这导致菌株水平上的个体间差异更高。此外，具有明显碳水化合物代谢潜力的不动的欧洲直肠真杆菌亚种在tCeD患者中几乎不存在。结论：我们的研究揭示了肠道微生物组与CeD之间复杂的相互作用，揭示了tCeD患者个体间变异和菌株水平变异的增加。这些发现扩大了我们对微生物组在肠道健康和疾病中的作用的理解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

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.