Gut Microbiota and Associated Mucosal Immune Response in Eosinophilic Granulomatosis with Polyangiitis (EGPA)
Elena Niccolai,
Alessandra Bettiol,
Simone Baldi,
Elena Silvestri,
Leandro Di Gloria,
Federica Bello,
Giulia Nannini,
Federica Ricci,
Maria Nicastro,
Matteo Ramazzotti,
Augusto Vaglio,
Gianluca Bartolucci,
Giacomo Emmi,
Amedeo Amedei,
Domenico Prisco
Affiliations
Elena Niccolai
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Alessandra Bettiol
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Simone Baldi
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Elena Silvestri
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Leandro Di Gloria
Department of Biomedical, Experimental and Clinical Sciences “Mario Serio” University of Florence, 50134 Florence, Italy
Federica Bello
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Giulia Nannini
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Federica Ricci
Core Research Laboratory, Institute for Cancer Research and Prevention (ISPRO), 50139 Florence, Italy
Maria Nicastro
Department of Medicine and Surgery, University of Parma and Unit of Occupational Medicine and Industrial Toxicology, University Hospital of Parma, 43121 Parma, Italy
Matteo Ramazzotti
Department of Biomedical, Experimental and Clinical Sciences “Mario Serio” University of Florence, 50134 Florence, Italy
Augusto Vaglio
Department of Biomedical, Experimental and Clinical Sciences “Mario Serio” University of Florence, 50134 Florence, Italy
Gianluca Bartolucci
Department of Neurosciences, Psychology, Drug Research and Child Health Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, 50139 Florence, Italy
Giacomo Emmi
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Amedeo Amedei
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Domenico Prisco
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A genome-wide association study showed a correlation between ANCA-negative EGPA and variants of genes encoding proteins with intestinal barrier functions, suggesting that modifications of the mucosal layer and consequent gut dysbiosis might be involved in EGPA pathogenesis. Here, we characterized the gut microbiota (GM) composition and the intestinal immune response in a cohort of EGPA patients. Faeces from 29 patients and 9 unrelated healthy cohabitants were collected, and GM and derived metabolites’ composition were compared. Seven intestinal biopsies from EGPA patients with gastrointestinal manifestations were analysed to assess the T-cell distribution and its correlation with GM and EGPA clinical and laboratory features. No significant differences in GM composition, nor in the total amount of faecal metabolites, emerged between patients and controls. Nevertheless, differences in bacterial taxa abundances and compositional GM-derived metabolites profile were observed. Notably, an enrichment of potential pathobionts (Enterobacteriacee and Streptococcaceae) was found in EGPA, 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. The analysis of the immune response in the gut mucosa revealed a high frequency of IFN-γ/IL-17-producing T lymphocytes, and a positive correlation between EGPA disease activity and intestinal T-cell levels. Our data suggest that an enrichment in potential intestinal pathobionts might drive an imbalanced inflammatory response in EGPA.
