Microbial Dysbiosis in Common Variable Immune Deficiencies: Evidence, Causes, and Consequences

Berbers, Roos-Marijn; Nierkens, Stefan; Laar, Jacob M van; Bogaert, Debby; Leavis, Helen L.

doi:10.1016/j.it.2016.11.008

Cited by 50 publications

(54 citation statements)

References 76 publications

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“…Previous studies have shown that immunodeficiency reshapes the native microbiome [72,73], and the microbiota plays a significant role in immunodeficiency diseases such as common variable immunodeficiency [74], which increases the host's susceptibility to infections. Additionally, ABT is able to modulate immune responses in mice (e.g., ref.…”

Section: Discussionmentioning

confidence: 99%

Selective colonization ability of human fecal microbes in different mouse gut environments

et al. 2018

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Mammalian hosts constantly interact with diverse exogenous microbes, but only a subset of the microbes manage to colonize due to selective colonization resistance exerted by host genetic factors as well as the native microbiota of the host. An important question in microbial ecology and medical science is if such colonization resistance can discriminate closely related microbial species, or even closely related strains of the same species. Using human-mouse fecal microbiota transplantation and metagenomic shotgun sequencing, we reconstructed colonization patterns of human fecal microbes in mice with different genotypes (C57BL6/J vs. NSG) and with or without an intact gut microbiota. We found that mouse genotypes and the native mouse gut microbiota both exerted different selective pressures on exogenous colonizers: human fecal Bacteroides successfully established in the mice gut, however, different species of Bacteroides selectively enriched under different gut conditions, potentially due to a multitude of functional differences, ranging from versatility in nutrient acquisition to stress responses. Additionally, different clades of Bacteroides cellulosilyticus strains were selectively enriched in different gut conditions, suggesting that the fitness of conspecific microbial strains in a novel host environment could differ.

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Section: Discussionmentioning

confidence: 99%

Selective colonization ability of human fecal microbes in different mouse gut environments

et al. 2018

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“…While T FH provide most of their function within germinal centers, it is notable that their increase is associated with germinal center enlargement and disorganization in CVID patients with autoimmunity (45). This increased T FH development has been linked with greater IgA deficiency and resultant endotoxemia, presumably due to bacterial translocation from mucosal surfaces in the absence of IgA (46). Expansion of T H17 cells has also been associated with autoimmunity in patients with CVID (47,48).…”

Section: Immunophenotypic Markers Associated With Autoimmunity In CVImentioning

confidence: 99%

“…The majority of cases may be polygenic, or perhaps better defined as simply multifactorial, with environmental, epigenetic, or other factors contributing. Over the past decade, the microbiome has been implicated in the manifestation of immune dysregulation (100), and has been explored in the pathogenesis of CVID complications (46).…”

Section: Microbiome In Cvid and Autoimmunitymentioning

confidence: 99%

Current Understanding and Recent Developments in Common Variable Immunodeficiency Associated Autoimmunity

Gereige

Maglione

2019

Front. Immunol.

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Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency and comprises a group of disorders with similar antibody deficiency but a myriad of different etiologies, most of which remain undefined. The variable aspect of CVID refers to the approximately half of patients who develop non-infectious complications in addition to heightened susceptibility to infection. The pathogenesis of these complications is poorly understood and somewhat counterintuitive because these patients that are defined by their immune futility simultaneously have elevated propensity for autoimmune disease. There are numerous aspects of immune dysregulation associated with autoimmunity in CVID that have only begun to be studied. These findings include elevations of T helper type 1 and follicular helper T cells and B cells expressing low levels of CD21 as well as reciprocal decreases in regulatory T cells and isotype-switched memory B cells. Recently, advances in genomics have furthered our understanding of the fundamental biology underlying autoimmunity in CVID and led to precision therapeutic approaches. However, these genetic etiologies are also associated with clinical heterogeneity and incomplete penetrance, highlighting the fact that continued research efforts remain necessary to optimize treatment. Additional factors, such as commensal microbial dysbiosis, remain to be better elucidated. Thus, while recent advances in our understanding of CVID-associated autoimmunity have been exciting and substantial, these current scientific advances must now serve as building blocks for the next stages of discovery.

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“…It is more likely that patients within the colonized cohort may not be able to mount a full host defense against infections, although there were no significant differences in the length of immunosuppressive therapy between the 2 groups. One underlying disorder may be microbial dysbiosis, 34 for which MDRO colonization could be a surrogate marker that results from previous loss of microbiotal diversity, or vice versa, for which MDRO colonization could be a predisposing factor that paves the way for the overgrowth of certain bacteria species. Recently, the role of gut microbiota in the HSCT setting has received increasing attention, and it has been demonstrated that HSCT strongly alters the composition of gut microbiota.…”

Section: Discussionmentioning

confidence: 99%

Clinical impact of colonization with multidrug‐resistant organisms on outcome after allogeneic stem cell transplantation in patients with acute myeloid leukemia

Scheich

Lindner

Koenig

et al. 2017

Cancer

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Microbial Dysbiosis in Common Variable Immune Deficiencies: Evidence, Causes, and Consequences

Cited by 50 publications

References 76 publications

Selective colonization ability of human fecal microbes in different mouse gut environments

Selective colonization ability of human fecal microbes in different mouse gut environments

Current Understanding and Recent Developments in Common Variable Immunodeficiency Associated Autoimmunity

Clinical impact of colonization with multidrug‐resistant organisms on outcome after allogeneic stem cell transplantation in patients with acute myeloid leukemia

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