The novel duodenal isolate Streptococcus salivarius AGIRA0003 promotes barrier dysfunction and IgG responses in functional dyspepsia
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Background and aims
Functional dyspepsia (FD) is a highly prevalent disorder of gut-brain interaction (DGBI) that is associated with an altered duodenal microbiota, unexplained low grade duodenal inflammation and altered intestinal permeability. This study aimed to investigate if novel FD-derived bacterial isolates elicited immune responses in FD and the capacity of an immune-stimulating isolate, AGIRA0003 to breach the duodenal epithelial barrier.
Methods
Bacterial lysates were investigated for immune reactivity using immunoblotting of patient plasma. Immunoblots were probed with plasma from FD patients (n=44, 46.6±17.5 years, 79.6% female) or controls (n=30, 48.9±15.7 years, 63.3% female). Peripheral gut-homing T cells were quantified by flow cytometry and histological analysis used to investigate duodenal biopsies. Polarised Caco-2 cells and FD duodenal spheroids (n=4 lines) were exposed to Streptococcus salivarius AGIRA0003 at a multiplicity of infection of 10 bacterial cells to 1 mammalian cell for 6 hours.
Results
The presence of plasma IgG antibodies against S. salivarius AGIRA0003 was significantly associated with FD (χ 2 15.7, 1, p <0.0001). Patients with these IgG antibodies had increased gut-homing lymphocytes (0.33±0.77% vs 1.00±1.46%, p =0.046). Strain AGIRA0003, but not related commensal strains, disrupted tight junction proteins in Caco-2 monolayers, and decreased claudin 1 (CLDN1; 0.49±0.11, p =0.03), desmocollin 2 (DSC2; 0.64±0.33, p =0.03) and desmoglein 2 (DSG2; 0.30±0.12, p =0.03) in spheroid monolayers. In addition, DSC2 (2.19±0.97 vs 1.48±0.85, p =0.02) and DSG2 (23.22±15.92 vs 12.38±7.34, p =0.04) protein levels were decreased in IgG + FD biopsies compared to controls.
Conclusions
S. salivarius AGIRA0003 is a potential pathobiont capable of impairing duodenal epithelial barrier defences that elicits an immune response in FD patients.
