Gut Microbiome and Common Variable Immunodeficiency: Few Certainties and Many Outstanding Questions

Abstract

Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody immunodeficiency, characterized by reduced serum levels of IgG, IgA, and/or IgM. The vast majority of CVID patients have polygenic inheritance. Immune dysfunction in CVID can frequently involve the gastrointestinal tract and lung. Few studies have started to investigate the gut microbiota profile in CVID patients. Overall, the results suggest that in CVID patients there is a reduction of alpha and beta diversity compared to controls. In addition, these patients can exhibit increased plasma levels of lipopolysaccharide (LPS) and markers (sCD14 and sCD25) of systemic immune cell activation. CVID patients with enteropathy exhibit decreased IgA expression in duodenal tissue. Mouse models for CVID unsatisfactorily recapitulate the polygenic causes of human CVID. The molecular pathways by which gut microbiota contribute to systemic inflammation and possibly tumorigenesis in CVID patients remain poorly understood. Several fundamental questions concerning the relationships between gut microbiota and the development of chronic inflammatory conditions, autoimmune disorders or cancer in CVID patients remain unanswered. Moreover, it is unknown whether it is possible to modify the microbiome and the outcome of CVID patients through specific therapeutic interventions.

Early Weaning and Milk Substitutes Affect the Gut Microbiome, Metabolomics, and Antibody Profile in Goat Kids Suffering From Diarrhea

“…We proposed that the decrease in IgG and IgM in DK could be caused by weaning as it decreases the antibody titer in lambs ( Napolitano et al, 1995 ). Diarrhea also could decrease circulating immunoglobulins lost through epithelial exudation in the area of gut mucosal damage ( Varricchi et al, 2021 ). Moreover, the greater relative abundance of Firmicutes and Firmicutes-to-Bacteroidetes ratio was identified in the DK group, and both were negatively correlated with IgG and IgM levels ( Shen et al, 2018 ).…”

Recurrent Campylobacter jejuni Infection in an Immunodeficient Patient Treated with Repeated Faecal Microbiota Transplant (FMT)—A Case Report

“…Nevertheless, this cannot fully explain the increased propensity, as patients with selective IgA deficiency alone are not at significantly increased risk. In addition, CVID patients are liable to develop more serious complications, including bacteraemia, as they lack bactericidal activity derived from plasma IgM [ 5 ] and have increased intestinal permeability, making bacterial translocation more likely [ 6 ].…”

Holistic Approach to Immune Checkpoint Inhibitor-Related Adverse Events

“…A clinical trial is prospectively analyzing the intestinal microbiome as predictor of ICI-associated irAEs (NCT04107311). Fecal microbiota transplant (FMT), which transfers an entire microbiome from a healthy donor to a recipient, is a therapeutic tool with several potential applications but numerous caveats ( 267 ). FMT may be a potential mechanism for treating ICI-induced colitis ( 258 ).…”