Academic Journal
Altered duodenal N6-methyladenosine levels in common variable immunodeficiency associate with duodenal microbiota.
| Τίτλος: | Altered duodenal N6-methyladenosine levels in common variable immunodeficiency associate with duodenal microbiota. |
|---|---|
| Συγγραφείς: | Myhre V; Division of Surgery and Specialized Medicine, Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Kaarbø M; Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway., Yang M; Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway.; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway., Fevang B; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Sousa MML; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.; Proteomics and Modomics Experimental Core Facility (PROMEC) at Norwegian University of Science and Technology, Trondheim, Norway., Reims HM; Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Lundin KEA; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Hov JR; Division of Surgery and Specialized Medicine, Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.; Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway., Aukrust P; Division of Surgery and Specialized Medicine, Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Bjørås M; Department of Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway.; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway., Jørgensen SF; Division of Surgery and Specialized Medicine, Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway. |
| Πηγή: | Frontiers in immunology [Front Immunol] 2026 Jul 08; Vol. 17, pp. 1875823. Date of Electronic Publication: 2026 Jul 08 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| Ιατρικοί όροι (MeSH): | Common Variable Immunodeficiency*/microbiology , Common Variable Immunodeficiency*/metabolism , Common Variable Immunodeficiency*/genetics , Common Variable Immunodeficiency*/immunology , Adenosine*/analogs & derivatives , Adenosine*/metabolism , Duodenum*/microbiology , Duodenum*/metabolism , Duodenum*/immunology , Microbiota*, Humans ; Female ; RNA Methylation ; Adult ; Male ; Epitranscriptome ; Middle Aged ; Epitranscriptomics |
| Περίληψη: | Introduction: Common variable immunodeficiency (CVID) is frequently complicated by duodenal inflammation, but the underlying molecular mechanisms remain poorly understood. While epigenetic alterations have been described in CVID, the epitranscriptome is largely unexplored. We therefore investigated whether RNA N6-methyladenosine (m6A) modifications in duodenal tissue are altered in CVID and whether such changes are associated with the local microbiota or m6A-related enzymes. Methods: m6A modification levels were analysed in snap-frozen duodenal biopsies from CVID patients with intraepithelial lymphocytosis and inflammation (CVID_IEL; n = 5), CVID patients with normal duodenal histology (CVID_N; n = 5) and controls with normal biopsies (n = 5) using m6A-RNA immunoprecipitation followed by microarray profiling and gene set enrichment analysis. Duodenal bacterial microbiota from the same anatomical region were characterised by 16S ribosomal RNA gene sequencing, and selected m6A-regulating enzymes were quantified in biopsies by targeted proteomics. Results: In total, 4,134 differentially methylated transcripts were identified, and unsupervised principal component analyses revealed partially overlapping, but clearly divergent m6A signatures for CVID_IEL, CVID_N and controls, with a gradient along the first principal component. Pathway analysis showed relative hypermethylation of mitochondria- and ribosome-related gene sets in both CVID subgroups versus controls, and hypomethylation of pathways linked to ubiquitination, proteasomal degradation, glycosylation and post-transcriptional gene silencing in CVID_IEL versus CVID_N. Sparse canonical correlation models demonstrated significant associations between specific duodenal bacterial genera and m6A-modified transcripts in CVID, but not in controls, whereas expression levels of the examined m6A-regulating enzymes did not differ between groups. Discussion: These findings suggest that duodenal inflammation in CVID may be associated with a distinct m6A epitranscriptomic signature that is linked to specific features of the mucosal microbiota, providing preliminary, hypothesis-generating evidence for a potential interaction between microbiota, epitranscriptomic regulation and local immune dysregulation in CVID. (Copyright © 2026 Myhre, Kaarbø, Yang, Fevang, Sousa, Reims, Lundin, Hov, Aukrust, Bjørås and Jørgensen.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors BF, PA declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. |
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| Contributed Indexing: | Keywords: CVID - common variable immunodeficiency; M6A modification; duodenum; epitranscriptome analysis; gastrointestinal diseases; m6A enzyme system; microbiota; primary immunodeficiencies (PID) |
| Substance Nomenclature: | K72T3FS567 (Adenosine) CLE6G00625 (N-methyladenosine) |
| Entry Date(s): | Date Created: 20260723 Date Completed: 20260723 Latest Revision: 20260813 |
| Update Code: | 20260814 |
| PubMed Central ID: | PMC13388135 |
| DOI: | 10.3389/fimmu.2026.1875823 |
| PMID: | 42488670 |
| Βάση Δεδομένων: | MEDLINE |
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