High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation
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 i...
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2489071 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jelle Slager |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-964ae693e7fd4636b5175a9c6d2a10dd |
| institution | DOAJ |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-964ae693e7fd4636b5175a9c6d2a10dd2025-08-20T03:15:13ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2489071High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variationJelle Slager0Hanna L. Simpson1Ranko Gacesa2Lianmin Chen3Ineke L. Tan4Jody Gelderloos5Astrid Maatman6Cisca Wijmenga7Alexandra Zhernakova8Jingyuan Fu9Rinse K. Weersma10Gieneke Gonera11Iris H. Jonkers12Sebo Withoff13Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsBackground 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.https://www.tandfonline.com/doi/10.1080/19490976.2025.2489071Coeliac diseasegut microbiomemetagenomic sequencingglutengluten-free diet |
| spellingShingle | 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 High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation Gut Microbes Coeliac disease gut microbiome metagenomic sequencing gluten gluten-free diet |
| title | High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation |
| title_full | High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation |
| title_fullStr | High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation |
| title_full_unstemmed | High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation |
| title_short | High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation |
| title_sort | high resolution analysis of the treated coeliac disease microbiome reveals strain level variation |
| topic | Coeliac disease gut microbiome metagenomic sequencing gluten gluten-free diet |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2489071 |
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