Lactobacillus acidophilus and propionate attenuate Sjögren’s syndrome by modulating the STIM1-STING signaling pathway

Abstract

Background Sjögren’s syndrome (SS) is an autoimmune disease characterized by inflammation of the exocrine gland. An imbalance of gut microbiota has been linked to SS. However, the molecular mechanism is unclear. We investigated the effects of Lactobacillus acidophilus (L. acidophilus) and propionate on the development and progression of SS in mouse model. Methods We compared the gut microbiomes of young and old mice. We administered L. acidophilus and propionate up to 24 weeks. The saliva flow rate and the histopathology of the salivary glands were investigated, and the effects of propionate on the STIM1-STING signaling pathway were evaluated in vitro. Results Lactobacillaceae and Lactobacillus were decreased in aged mice. SS symptoms were ameliorated by L. acidophilus. The abundance of propionate-producing bacterial was increased by L. acidophilus. Propionate ameliorated the development and progression of SS by inhibiting the STIM1-STING signaling pathway. Conclusions The findings suggest that Lactobacillus acidophilus and propionate have therapeutic potential for SS.

Insights into Microbiota in Sjögren’s Syndrome

“…Dysbiosis of the intestinal microbiota induces SS by enhancing lymphocyte infiltration into the salivary glands and by stimulating stromal interaction molecule type 1—the interferon gene stimulator-type I interferon axis (STIM1-STING-IFN axis). These results provide support for the idea that Lactobacillus acidophilus and propionate have a therapeutic potential for the treatment of SS [ 66 ]. Several studies have shown that commensal oral and intestinal bacteria are cross-reactive with SSA/Ro60, and this is critical for the development of SS.…”

Over-activation of STING Induces Endoplasmic Reticulum Stress and Apoptosis via Binding Affinity with IP3R in Salivary Gland Cells of Sjögren's Syndrome

“…Excessive activation of STING can lead to numerous autoimmune or in ammatory diseases, such as SLE, experimental autoimmune encephalomyelitis (EAE, mouse model of multiple sclerosis), and Aicardi-Goutières syndrome (31,32). Additionally, studies have suggested that Lactobacillus reuteri and propionate alleviate SS symptoms by modulating the STING signaling pathway (33,34). Therefore, the potential value of STING as a therapeutic target warrants further research and exploration.…”