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

Daniel F. Zegarra-Ruiz, Asmaa El Beidaq, Alonso J. Iñiguez, Martina Lubrano Di Ricco, Silvio Manfredo Vieira, William E. Ruff, Derek Mubiru, Rebecca L. Fine, John Sterpka, Teri Greiling, Carina Dehner, Martin A. Kriegel

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)113-127.e6
JournalCell Host and Microbe
Volume25
Issue number1
DOIs
StatePublished - Jan 9 2019
Externally publishedYes

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Keywords

  • Clostridiaceae
  • Clostridiales
  • gut microbiota
  • human SLE microbiome
  • interferon
  • Lactobacillus
  • Lactobacillus reuteri
  • plasmacytoid dendritic cells
  • resistant starch
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

Cite this

Zegarra-Ruiz, D. F., El Beidaq, A., Iñiguez, A. J., Lubrano Di Ricco, M., Manfredo Vieira, S., Ruff, W. E., Mubiru, D., Fine, R. L., Sterpka, J., Greiling, T., Dehner, C., & Kriegel, M. A. (2019). A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity. Cell Host and Microbe, 25(1), 113-127.e6. https://doi.org/10.1016/j.chom.2018.11.009