Gut Microbiota and Associated Mucosal Immune Response in Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Niccolai, Elena; Bettiol, Alessandra; Baldi, Simone; Silvestri, Elena; Gloria, Leandro Di; Bello, Federica; Nannini, Giulia; Ricci, Francesca; Nicastro, Maria; Ramazzotti, Matteo; Vaglio, Augusto; Bartolucci, Gianluca; Emmi, Giacomo; Amedei, Amedeo; Prisco, Domenico

doi:10.3390/biomedicines10061227

Cited by 6 publications

(3 citation statements)

References 50 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, an enrichment of potential pathobionts (Enterobacteriacee and Streptococcaceae) was found in Eosinophilic Granulomatosis with Polyangiitis ( 23 )., particularly in patients with active disease, while lower levels were found in patients on immunosuppression, compared with non-immunosuppressed ones. Significantly lower amounts of hexanoic acid were found in patients, compared to controls.…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota and immune mediation: a Mendelian randomization study on granulomatosis with polyangiitis

Chen,

Tang

2023

Front. Immunol.

View full text Add to dashboard Cite

BackgroundThe gut microbiota plays a pivotal role in influencing various health outcomes, including immune-mediated conditions. Granulomatosis with Polyangiitis (GPA) is one such condition, and its potential associations with gut microbiota remain underexplored.MethodUsing a two-sample Mendelian randomization approach, we investigated the causal links between gut microbiota and GPA. We sourced our data from multiple cohorts and consortiums, including the MiBioGen consortium. Our study design incorporated both direct associations and mediation effects of immune traits on the relationship between gut microbiota and GPA.ResultsOur analysis revealed significant associations between 1 phylum, 1 family 9 genus microbiota taxa and GPA. Furthermore, we identified several immune cell traits that mediated the effects of gut microbiota on GPA. For instance, the family Defluviitaleaceae and genus Defluviitaleaceae UCG011 influenced GPA through CD11c in granulocytes. The mediation effect proportions further elucidated the complex dynamics between gut microbiota exposures, immune markers, and their combined influence on GPA.ConclusionOur findings underscore the intricate relationship between gut microbiota, immune markers, and GPA. The identified associations and mediation effects provide valuable insights into the potential therapeutic avenues targeting gut microbiota to manage GPA.

show abstract

Section: Discussionmentioning

confidence: 99%

Gut microbiota and immune mediation: a Mendelian randomization study on granulomatosis with polyangiitis

Chen,

Tang

2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…A recent study demonstrated an association between occupational exposures to organic solvents, silica, and farming and the risk of EGPA [22], while tobacco exposure resulted protective particularly in ANCA-negative EGPA, by suppressing the immune system at mucosal level. The role of mucosal disfunction in EGPA is also supported by the evidence of an imbalance in gut mucosal immune response secondary to an enrichment of intestinal pathobionts [23].…”

Section: Eosinophilic Granulomatosis With Polyangiitis Pathophysiologymentioning

confidence: 89%

Biologics for eosinophilic granulomatosis with polyangiitis

Caminati

Maule

Bello

et al. 2022

Current Opinion in Allergy &Amp; Clinical Immunology

Self Cite

View full text Add to dashboard Cite

Purpose of reviewThe link between severe asthma and eosinophilic granulomatosis with polyangiitis (EGPA) in terms of pathophysiological background, clinical manifestations and disease evolution has leaded to investigate the relevance of anti T2 monoclonal antibodies licensed for severe asthma patients as a treatment option for EGPA. The present review aimed to provide un update on EGPA pathophysiology and to critically summarize the most robust evidence coming from trials and real-life setting on the use of anti T2 biologics in EGPA patients.Recent findingsMepolizumab, an anti-interleukin-5 monoclonal antibody, is the only biologic drug targeting eosinophilic inflammation currently approved for EGPA treatment at the dose of 300 mg/4 weeks. Its use is restricted by the American College of Rheumatology guidelines to specific diseases phases and severity grades. However the most appropriate mepolizumab positioning and dose is still under investigation in the real life practice, which is providing an increasing amount of evidence confirming its efficacy, alone or in combination with other options in different disease stages. The relevance of other monoclonal antibodies interfering with T2 inflammation, including omalizumab and benralizumab, is under investigation but the evidence is still scarceSummaryTaking into account the suboptimal medium-long term safety profile of conventional EGPA treatments, the opportunity of selectively targeting eosinophilic inflammation certainly represents a revolutionary approach. However, further real-word evidence is required to effectively position the new treatments in the light of the disease complexity, including different immunological drivers, and individual variability.

show abstract

“…Recent research is now suggesting the existence of a two-way association between microbiota and the variability of many human traits. Indeed, dysbiosis—defined as an imbalance in microbiota profiles—has been associated with a range of complex diseases, including metabolic, immune, neurodegenerative, and neurological diseases [ 8 , 9 , 10 , 11 ]. Nonetheless, the underlying mechanisms of the reciprocal influence among individual or communities of microorganisms and human health are puzzling and need to be further clarified.…”

mentioning

confidence: 99%