Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation
Abstract Background Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and recurrent infections. Significant morbidity and mortality are caused by immune dysregulation complications (CVIDid), which affect around one-third of CVID patients and have a poorly understood e...
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BMC
2025-01-01
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| Online Access: | https://doi.org/10.1186/s40168-024-01982-y |
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| author | Roos-Marijn Berbers Fernanda L. Paganelli Joris M. van Montfrans Pauline M. Ellerbroek Marco C. Viveen Malbert R. C. Rogers Moniek Salomons Jaap Schuurmans Martine van Stigt Thans Remi M. M. Vanmaris Lodewijk A. A. Brosens Maria Marlot van der Wal Virgil A. S. H. Dalm P. Martin van Hagen Annick A. J. M. van de Ven Hae-Won Uh Femke van Wijk Rob J. L. Willems Helen L. Leavis |
| author_facet | Roos-Marijn Berbers Fernanda L. Paganelli Joris M. van Montfrans Pauline M. Ellerbroek Marco C. Viveen Malbert R. C. Rogers Moniek Salomons Jaap Schuurmans Martine van Stigt Thans Remi M. M. Vanmaris Lodewijk A. A. Brosens Maria Marlot van der Wal Virgil A. S. H. Dalm P. Martin van Hagen Annick A. J. M. van de Ven Hae-Won Uh Femke van Wijk Rob J. L. Willems Helen L. Leavis |
| author_sort | Roos-Marijn Berbers |
| collection | DOAJ |
| description | Abstract Background Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and recurrent infections. Significant morbidity and mortality are caused by immune dysregulation complications (CVIDid), which affect around one-third of CVID patients and have a poorly understood etiology. Here, we investigate the hypothesis that gut microbial dysbiosis contributes to the inflammation underlying CVIDid. Results Bacterial invasion of colonic crypts was observed in CVID (3/15) and X-linked agammaglobulinemia (XLA, 1/3), but not in healthy control (HC, 0/9) biopsies. Fecal gut microbiota was characterized using 16S rRNA-targeted amplicon sequencing. Increased bacterial load, decreased alpha diversity and distinct beta diversity were observed in CVIDid (n = 42) compared to HC (n = 48), and similar results were seen in CVID with IgA deficiency (n = 40) compared to HC. CVIDid and CVID-IgA showed enrichment of the genus Enterococcus, and in vitro studies confirmed the inflammatory potential of Enterococcus gallinarum and Enterococcus hirae in patient monocytes. Conclusions This study further supports the hypothesis that a dysregulated gut microbiota, with IgA deficiency as an important driving factor, contributes to systemic inflammation in primary antibody deficiency, and introduces enterococci as potential pathobionts in CVIDid. Video Abstract |
| format | Article |
| id | doaj-art-72a404cdfa474b8cb6b8f1b637af96bf |
| institution | Kabale University |
| issn | 2049-2618 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbiome |
| spelling | doaj-art-72a404cdfa474b8cb6b8f1b637af96bf2025-01-19T12:32:34ZengBMCMicrobiome2049-26182025-01-0113111710.1186/s40168-024-01982-yGut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulationRoos-Marijn Berbers0Fernanda L. Paganelli1Joris M. van Montfrans2Pauline M. Ellerbroek3Marco C. Viveen4Malbert R. C. Rogers5Moniek Salomons6Jaap Schuurmans7Martine van Stigt Thans8Remi M. M. Vanmaris9Lodewijk A. A. Brosens10Maria Marlot van der Wal11Virgil A. S. H. Dalm12P. Martin van Hagen13Annick A. J. M. van de Ven14Hae-Won Uh15Femke van Wijk16Rob J. L. Willems17Helen L. Leavis18Department of Medical Microbiology, University Medical Center Utrecht and Utrecht UniversityDepartment of Medical Microbiology, University Medical Center Utrecht and Utrecht UniversityDepartment of Pediatric Immunology and Infectious Diseases, University Medical Center Utrecht and Utrecht UniversityDepartment of Internal Medicine and Infectious Diseases, University Medical Center Utrecht and Utrecht UniversityDepartment of Medical Microbiology, University Medical Center Utrecht and Utrecht UniversityDepartment of Medical Microbiology, University Medical Center Utrecht and Utrecht UniversityDepartment of Medical Microbiology, University Medical Center Utrecht and Utrecht UniversityDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht and Utrecht UniversityDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht and Utrecht UniversityDepartment of Medical Microbiology, University Medical Center Utrecht and Utrecht UniversityDepartment of Pathology, University Medical Center Utrecht and Utrecht UniversityCenter for Translational Immunology, University Medical Center Utrecht and Utrecht UniversityDepartment of Internal Medicine, Division of Clinical Immunology, Erasmus MC University Medical CenterDepartment of Internal Medicine, Division of Clinical Immunology, Erasmus MC University Medical CenterDepartments of Internal Medicine and Allergology, Rheumatology and Clinical Immunology, University Medical Center GroningenDepartment of Data Science and Biostatistics, Julius Center, University Medical Center Utrecht and Utrecht UniversityCenter for Translational Immunology, University Medical Center Utrecht and Utrecht UniversityDepartment of Medical Microbiology, University Medical Center Utrecht and Utrecht UniversityDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht and Utrecht UniversityAbstract Background Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and recurrent infections. Significant morbidity and mortality are caused by immune dysregulation complications (CVIDid), which affect around one-third of CVID patients and have a poorly understood etiology. Here, we investigate the hypothesis that gut microbial dysbiosis contributes to the inflammation underlying CVIDid. Results Bacterial invasion of colonic crypts was observed in CVID (3/15) and X-linked agammaglobulinemia (XLA, 1/3), but not in healthy control (HC, 0/9) biopsies. Fecal gut microbiota was characterized using 16S rRNA-targeted amplicon sequencing. Increased bacterial load, decreased alpha diversity and distinct beta diversity were observed in CVIDid (n = 42) compared to HC (n = 48), and similar results were seen in CVID with IgA deficiency (n = 40) compared to HC. CVIDid and CVID-IgA showed enrichment of the genus Enterococcus, and in vitro studies confirmed the inflammatory potential of Enterococcus gallinarum and Enterococcus hirae in patient monocytes. Conclusions This study further supports the hypothesis that a dysregulated gut microbiota, with IgA deficiency as an important driving factor, contributes to systemic inflammation in primary antibody deficiency, and introduces enterococci as potential pathobionts in CVIDid. Video Abstracthttps://doi.org/10.1186/s40168-024-01982-yCommon variable immunodeficiency (CVID)Immune dysregulationGut microbiotaPathobionts |
| spellingShingle | Roos-Marijn Berbers Fernanda L. Paganelli Joris M. van Montfrans Pauline M. Ellerbroek Marco C. Viveen Malbert R. C. Rogers Moniek Salomons Jaap Schuurmans Martine van Stigt Thans Remi M. M. Vanmaris Lodewijk A. A. Brosens Maria Marlot van der Wal Virgil A. S. H. Dalm P. Martin van Hagen Annick A. J. M. van de Ven Hae-Won Uh Femke van Wijk Rob J. L. Willems Helen L. Leavis Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation Microbiome Common variable immunodeficiency (CVID) Immune dysregulation Gut microbiota Pathobionts |
| title | Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation |
| title_full | Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation |
| title_fullStr | Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation |
| title_full_unstemmed | Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation |
| title_short | Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation |
| title_sort | gut microbial dysbiosis iga and enterococcus in common variable immunodeficiency with immune dysregulation |
| topic | Common variable immunodeficiency (CVID) Immune dysregulation Gut microbiota Pathobionts |
| url | https://doi.org/10.1186/s40168-024-01982-y |
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