Bacterial but Not Fungal Gut Microbiota Alterations Are Associated With Common Variable Immunodeficiency (CVID) Phenotype

Abstract

Common Variable Immunodeficiency (CVID) is the most frequent symptomatic immune disorder characterized by reduced serum immunoglobulins. Patients often suffer from infectious and serious non-infectious complications which impact their life tremendously. The monogenic cause has been revealed in a minority of patients so far, indicating the role of multiple genes and environmental factors in CVID etiology. Using 16S and ITS rRNA amplicon sequencing, we analyzed the bacterial and fungal gut microbiota, respectively, in a group of 55 participants constituting of CVID patients and matched healthy controls including 16 case-control pairs living in the same household, to explore possible associations between gut microbiota composition and disease phenotype. We revealed less diverse and significantly altered bacterial but not fungal gut microbiota in CVID patients, which additionally appeared to be associated with a more severe disease phenotype. The factor of sharing the same household impacted both bacterial and fungal microbiome data significantly, although not as strongly as CVID diagnosis in bacterial assessment. Overall, our results suggest that gut bacterial microbiota is altered in CVID patients and may be one of the missing environmental drivers contributing to some of the symptoms and disease severity. Paired samples serving as controls will provide a better resolution between disease-related dysbiosis and other environmental confounders in future studies.

Altered Microbiota, Impaired Quality of Life, Malabsorption, Infection, and Inflammation in CVID Patients With Diarrhoea

“…Also, CVID patients in general had a lower alpha diversity than healthy controls (21). This was also observed by Fiedorova et al (25). In our study, a significant difference in alpha diversity could be shown between CVID patients and healthy donors as well as between CVID patients with non-infectious diarrhoea and those without diarrhoea.…”

“…So far, only few investigations of the CVID microbiome have been published (21)(22)(23)(24)(25)(26). The diversity of microbiota within one individual or its sample (alpha diversity) and the differences in distribution of different microbiota among samples or individuals (beta diversity) can be described.…”

Gut Microbiota–Host Interactions in Inborn Errors of Immunity

“…Non-infectious complications of CVID are mainly caused by immune dysregulation. This chronic and aberrant systemic immune activation seems to be, at least in part, a consequence of increased microbial translocation [ 61 , 124 , 125 ]. Jørgensen et al investigated gut microbiota composition in 44 CVID patients, 45 patients with IBD and 263 healthy controls [ 126 ].…”

Histopathology of Celiac Disease. Position Statements of the Italian Group of Gastrointestinal Pathologists (Gipad-Siapec)

“…Other reported conditions associated with an increased number of IELs include Hashimoto thyroiditis, Graves' disease, rheumatoid arthritis, psoriasis, multiple sclerosis, and systemic lupus erythematosus. Common variable immune deficiency also causes intestinal mucosal damage due to inflammation and/or infections [36]. Furthermore, chronic inflammatory bowel diseases and collagenous and lymphocytic colitis have been concurrently associated with proximal small intestinal intraepithelial lymphocytosis.…”