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

Cell Host Microbe. 2019 Jan 9;25(1):113-127.e6. doi: 10.1016/j.chom.2018.11.009. Epub 2018 Dec 20.


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 16S 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.

Keywords: Clostridiaceae; Clostridiales; Lactobacillus; Lactobacillus reuteri; gut microbiota; human SLE microbiome; interferon; plasmacytoid dendritic cells; resistant starch; systemic lupus erythematosus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity*
  • Clostridiaceae
  • DNA, Ribosomal / genetics
  • Dendritic Cells / metabolism
  • Diet Therapy
  • Diet*
  • Disease Models, Animal
  • Fatty Acids, Volatile / antagonists & inhibitors
  • Fatty Acids, Volatile / metabolism
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome
  • Germ-Free Life
  • Glomerulonephritis / pathology
  • Humans
  • Hypersensitivity*
  • Interferon Type I / metabolism
  • Kidney / pathology
  • Lactobacillus / drug effects
  • Lactobacillus / genetics
  • Lactobacillus / pathogenicity*
  • Lactobacillus reuteri
  • Lupus Erythematosus, Systemic / microbiology*
  • Lupus Erythematosus, Systemic / mortality
  • Lupus Erythematosus, Systemic / pathology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Ribosomal, 16S / genetics
  • Starch
  • Survival Rate
  • Toll-Like Receptor 7 / metabolism*


  • DNA, Ribosomal
  • Fatty Acids, Volatile
  • Interferon Type I
  • Membrane Glycoproteins
  • RNA, Ribosomal, 16S
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Starch