Dysbiosis of the gut microbiota may play a role in driving systemic inflammation in patients with primary antibody deficiencies, according to a Dutch multicenter study coordinated by UMC Utrecht. In addition, enterococci may act as potential pathobionts that could exacerbate immune dysregulation in primary immune deficiencies, highlighting the need for further research into the gut microbiome’s impact on immune health in these patients.
Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by hypogammaglobulinemia and increased susceptibility to infections. A significant proportion of CVID patients experience complications related to immune dysregulation (CVIDid), leading to substantial morbidity and mortality. The underlying mechanisms of these complications remain poorly understood, prompting investigation into potential contributions from gut microbial dysbiosis. In a clinical study, published this month in Microbiome, an interdisciplinary group of researchers from UMC Utrecht, Erasmus MC and UMC Groningen investigated the hypothesis that gut microbial dysbiosis contributes to the inflammation underlying CVIDid.
Principal investigator Helen Leavis, MD PhD (internist-immunologist and associate professor at the Department of Rheumatology and Clinical Immunology, UMC Utrecht) concluded: “The findings of our study support the hypothesis that dysbiosis of the gut microbiota, particularly in the context of IgA deficiency, may play a role in driving systemic inflammation in patients with primary antibody deficiencies. The study introduces enterococci as potential pathobionts that could exacerbate immune dysregulation in CVIDid. This highlights the need for further research into the gut microbiome’s impact on immune health in this patient population. Therapeutic targeting of gut pathobionts may be a promising outlook in the prevention and treatment of immune dysregulation in CVID.”
Common variable immunodeficiency (CVID) is a rare, chronic immune disorder characterized by low antibody levels (specifically of immunoglobulins IgG, IgM and IgA). Symptoms include increased risk of (recurrent) infections which may lead to chronic lung disease. Non-infectious complications include autoimmunity, chronic inflammation of for instance lungs and gastrointestinal tract and lymphoproliferation associated with an increased risk of malignant lymphoma. The underlying causes are largely obscure, but genetic factors have been identified as the cause of CVID in about 10 percent of patients. CVID has an estimated prevalence of about 1 in 50,000 in Caucasians, but seems less prevalent amongst Asians and African-Americans.
Berbers R-M, Paganelli FL, Montfrans JM van, Ellerbroek PM, Viveen MC, Rogers MRC, Salomons M, Schuurmans J, Stigt Thans M van, Vanmaris RMM, Brosens LAA, Wal MM van der, Dalm VASH, Hagen PM van, Ven AAJM van de, Uh H-W, Wijk F van, Willems RJL, Leavis HL. Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation. Microbiome 2025;13:12.
