Abstract
Common variable immunodeficiency (CVID) is a clinically and genetically heterogeneous disorder with inadequate antibody responses and low levels of immunoglobulins including IgA that is involved in the maintenance of the intestinal homeostasis. In this study, we analyzed the taxonomical and functional metagenome of the fecal microbiota and stool metabolome in a cohort of six CVID patients without gastroenterological symptomatology and their healthy housemates. The fecal microbiome of CVID patients contained higher numbers of bacterial species and altered abundance of thirty-four species. Hungatella hathewayi was frequent in CVID microbiome and absent in controls. Moreover, the CVID metagenome was enriched for low-abundance genes likely encoding nonessential functions, such as bacterial motility and metabolism of aromatic compounds. Metabolomics revealed dysregulation in several metabolic pathways, mostly associated with decreased levels of adenosine in CVID patients. Identified features have been consistently associated with CVID diagnosis across the patients with various immunological characteristics, length of treatment, and age. Taken together, this initial study revealed expansion of bacterial diversity in the host immunodeficient conditions and suggested several bacterial species and metabolites, which have potential to be diagnostic and/or prognostic CVID markers in the future.
Highlights
The human gut microbiome is a complex microbial ecosystem significantly contributing to the host physiology
Despite the above-mentioned limitations, this study shows a detailed intestinal Common variable immunodeficiency (CVID) microbiome composition with minimalized effect of environment and CVID-related intestinal complications
We have identified increased bacterial diversity in conditions of host immunodeficiency, especially at the level of bacterial species and encoded variable nonessential gene functions
Summary
The human gut microbiome is a complex microbial ecosystem significantly contributing to the host physiology. A number of factors including host genetics, age, diet, and antibiotic exposure can change the composition of the gut microbiota. Since the gut microbiota modulates the host immune system, a microbial dysbiosis was found in immune conditions including allergy, asthma, atherosclerosis, and multiple sclerosis. CVID includes clinically and genetically heterogeneous disorders characterized by a defect in B cell differentiation leading to inadequate antibody responses and low levels of immunoglobulin G (IgG) and IgA, and, inconsistently, IgM. The current therapy is based on administration of IgG and, in some patients, immunosuppression, in order to manage the infectious and autoimmune complications, respectively [reviewed in [5,6,7,8,9]]
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