The Effect of Lacticaseibacillus paracasei on the Severity of Epstein-Barr Virus DNA-Exacerbated Arthritis in a Mouse Model

Abstract

Epstein-Barr virus (EBV) infection is known to have periods of latency and reactivation accompanied by the shedding of EBV DNA; this may induce proinflammatory immune responses leading to the development of autoimmune diseases such as rheumatoid arthritis (RA). RA is an autoinflammatory disease that causes destruction in the joints and could lead to disability and early death. Previous studies conducted in out laboratory have shown that EBV DNA aggravates the severity of arthritis and changes the composition of the gut microbiota, specifically within the Lactobacillaceae family in the collagen-induced arthritis (CIA) mouse model. With evidence that the viral DNA affects the gut-joint axis in RA and considering the immunomodulatory ability of probiotics, the current study sought to determine the effects of Lacticaseibacillus paracasei (L. paracasei) on the severity of EBV DNA-exacerbated arthritis in a CIA mouse model.

Female C57BL/6J mice, 10 weeks of age, were treated with either type II chicken collagen, collagen and EBV DNA, collagen and EBV DNA in combination with L. paracasei, or collagen and L. paracasei. Arthritis severity was evaluated by measurements of hind paw thickness, clinical scoring, and grip strength. The colon length, as an indicator of systemic inflammation, was measured during the sacrifice. Histopathological scoring was carried out on footpad, ankle joint, and colon sections. Ankle joint, footpad, and colon tissues were stained for interleukin-17A (IL-17A), interferon-gamma (IFN-γ), and Forkhead box P3 (FOXP3) and quantified using immunofluorescence and confocal microscopy.

A significant reduction in paw thickness, clinical arthritis scores, and histological scores, alongside a marked improvement in grip strength, was observed in the groups that received EBV DNA, collagen, and L. paracasei, as compared to mice treated with EBV DNA and collagen. In addition, the colon length of L. paracasei-treated groups was significantly increased compared to controls. Moreover, L. paracasei-treated groups had a statistically significant reduction in the number of pathogenicity-associated IL-17A+IFN-γ+ and 17A+IFN-γ+ FOXP3+ foci in footpad, ankle joint, and colon sections.

This study reveals that L. paracasei can significantly reduce the severity of EBV DNA-exacerbated arthritis in a CIA mouse model, resulting in reduced joint inflammation, intestinal damage, and detection of pathogenicity-associated markers.