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

Apr 28, 2025

Experts: 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

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.
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.
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 , , and , 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 , which has a distinct carbohydrate metabolism potential, was nearly absent in tCeD patients.
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.

Author

admin

View all posts

ABOUT THE EXPERTS

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

Jelle Slager

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Hanna L Simpson

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Ranko Gacesa

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Lianmin Chen

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Department of Cardiology, Nanjing Medical University, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Cardiovascular Research Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.

Ineke L Tan

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Jody Gelderloos

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Astrid Maatman

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Cisca Wijmenga

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Alexandra Zhernakova

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Jingyuan Fu

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Rinse K Weersma

Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Gieneke Gonera

Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Department of Pediatrics, Wilhelmina Hospital Assen, Assen, The Netherlands.

Iris H Jonkers

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Sebo Withoff

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.