Highlights
•
L.
reuteri colonizes lupus-prone hosts and translocates to MLN, liver, and spleen
•
L.
reuteri exacerbates TLR7-dependent lupus in conventional and germ-free mice
• Resistant starch ameliorates pDCs, type I IFN pathways, and lupus-related mortality
• Starch diet-derived short-chain fatty acids suppress
L.
reuteri in vitro and
in vivo
Summary
Western lifestyle is linked to autoimmune and metabolic diseases, driven by changes in diet and
gut microbiota composition. Using
Toll-like receptor 7 (TLR7)-dependent mouse models of
systemic lupus erythematosus (SLE), we dissect dietary effects on the gut microbiota and find that
Lactobacillus reuteri can drive
autoimmunity but is ameliorated by dietary resistant
starch (RS). Culture of internal organs and 16
S rDNA sequencing revealed TLR7-dependent translocation of
L. reuteri in mice and fecal enrichment of
Lactobacillus in a subset of SLE patients.
L.
reuteri colonization worsened autoimmune manifestations under specific-pathogen-free and
gnotobiotic conditions, notably increasing
plasmacytoid dendritic cells (pDCs) and
interferon signaling.
However, RS suppressed the abundance and translocation of
L.
reuteri via short-chain fatty acids, which inhibited its growth. Additionally, RS decreased pDCs, interferon pathways, organ involvement, and mortality. Thus, RS exerts beneficial effects in lupus-prone hosts through suppressing a pathobiont that promotes interferon pathways implicated in the pathogenesis of human autoimmunity.
