A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity

Area of Science:

• Immunology
• Microbiology
• Gastroenterology

Background:

• Western lifestyles are associated with increased autoimmune and metabolic diseases.
• Diet and gut microbiota composition play crucial roles in disease pathogenesis.
• Systemic lupus erythematosus (SLE) is an autoimmune disease with complex triggers.

Purpose of the Study:

• To investigate the impact of diet on gut microbiota and autoimmunity in a mouse model of SLE.
• To determine the role of Lactobacillus reuteri in driving autoimmune responses.
• To evaluate the therapeutic potential of resistant starch (RS) in mitigating L. reuteri-induced autoimmunity.

Main Methods:

• Utilized Toll-like receptor 7 (TLR7)-dependent mouse models of SLE.
• Analyzed gut microbiota composition using 16S rDNA sequencing.
• Assessed bacterial translocation via organ culture.
• Quantified immune cell populations (e.g., plasmacytoid dendritic cells) and interferon signaling pathways.

Main Results:

• Lactobacillus reuteri was identified as a driver of autoimmunity in SLE models.
• TLR7-dependent translocation of L. reuteri was observed in mice and linked to SLE patients.
• Resistant starch (RS) suppressed L. reuteri abundance and translocation through short-chain fatty acids.
• RS ameliorated autoimmune manifestations, including reduced pDCs, interferon signaling, organ involvement, and mortality.

Conclusions:

• Resistant starch (RS) demonstrates a beneficial effect in lupus-prone hosts by suppressing the pathobiont L. reuteri.
• RS mitigates autoimmunity by inhibiting L. reuteri growth and translocation, thereby reducing interferon pathway activation.
• Dietary interventions targeting gut microbiota may offer novel therapeutic strategies for autoimmune diseases like SLE.