A diet-sensitive commensal Lactobacillus strain mediates TLR7-dependent systemic autoimmunity.

Autoimmune host-microbiota interactions modulated by diet remain ill defined. We dissected dietary resistant starch effects on the gut microbiota in a spontaneous and inducible lupus model dependent on toll-like receptor 7 (TLR7). Resistant starch decreased lupus-related plasmacytoid dendritic cells, interferon pathways, organ involvement and mortality. Culture of internal organs and 16S rDNA sequencing revealed TLR7-dependent translocation of Lactobacillus reuteri. L. reuteri gavage worsened autoimmune manifestations under specific-pathogen-free and gnotobiotic conditions. Resistant starch suppressed the abundance and translocation of L. reuteri via ileal short-chain fatty acids, which inhibited L. reuteri growth. In summary, resistant starch exerts beneficial effects in lupus-prone hosts through suppression of a pathobiont that mediates type I interferon pathways implicated in the pathogenesis of human autoimmune diseases. This study provides mechanistic insights into diet-host-microbiota interactions and links a gut pathobiont to TLR7-dependent systemic inflammation, which may aid in the development of functional diets to treat autoimmune diseases.