Gut Microbial Dysbiosis, IgA, and Enterococcus in Common Variable Immunodeficiency with Immune Dysregulation

Overview

Journal Microbiome

Publisher Biomed Central

Date 2025 Jan 17

PMID 39819634

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Intestinal Microbiota Dysbiosis Role and Bacterial Translocation as a Factor for Septic Risk.

Charitos I, Scacco S, Cotoia A, Castellaneta F, Castellana G, Pasqualotto F Int J Mol Sci. 2025; 26(5).

PMID: 40076650 PMC: 11900423. DOI: 10.3390/ijms26052028.

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