Pathophysiology of the gut–eye axis in a Sjögren's disease‐like dry eye mouse model: An exploratory evaluation of dietary heat‐treated Enterococcus faecalis FK‐23

Abstract

Sjögren's disease is an autoimmune disease characterized by severe dry eye, but its pathophysiology remains unclear. Non‐obese diabetic (NOD) mice develop Sjögren's disease‐like dry eye prior to the onset of diabetes. Although intestinal immune abnormalities precede diabetes in NOD mice, their relationship to dry eye remains poorly understood. This study investigated pathological changes in the lacrimal gland (LG) and small intestine of NOD mice and evaluated the potential effects of dietary heat‐treated Enterococcus faecalis FK‐23 (FK‐23). Four‐week‐old male NOD mice were fed either a standard diet or a diet containing 3% FK‐23 for 2 weeks. BALB/c mice served as controls. Tear secretion was measured following pilocarpine administration. LG and small intestine tissues were analysed histologically, and intestinal lymphocytes were evaluated by flow cytometry and next‐generation sequencing. At 4 weeks of age, NOD mice exhibited normal tear secretion and no apparent LG inflammation but showed reduced small intestinal crypt granules and decreased proportions of ILC3 and T helper 17 cells. At 6 weeks, NOD mice demonstrated reduced tear secretion, inflammatory cell infiltration in the LG, and loss of crypt granules and goblet cells in the small intestine. Dietary FK‐23 administration showed trends towards attenuating tear secretion decline, LG inflammation and intestinal pathological changes. Development of LG inflammation and dry eye in NOD mice was associated with intestinal immune and epithelial abnormalities. These findings suggest potential involvement of the gut–eye axis in Sjögren's disease‐like dry eye pathogenesis and indicate that modulation of intestinal homeostasis might represent a therapeutic strategy.