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 M. Greiling; Carina Dehner; Martin A. Kriegel

doi:10.1016/j.chom.2018.11.009

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 M. Greiling, Carina Dehner, Martin A. Kriegel

Research output: Contribution to journal › Article › peer-review

194 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 language	English (US)
Pages (from-to)	113-127.e6
Journal	Cell Host and Microbe
Volume	25
Issue number	1
DOIs	https://doi.org/10.1016/j.chom.2018.11.009
State	Published - Jan 9 2019
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

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10.1016/j.chom.2018.11.009

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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. M., 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

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title = "A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity",

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.",

keywords = "Clostridiaceae, Clostridiales, Lactobacillus, Lactobacillus reuteri, gut microbiota, human SLE microbiome, interferon, plasmacytoid dendritic cells, resistant starch, systemic lupus erythematosus",

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AU - Zegarra-Ruiz, Daniel F.

AU - El Beidaq, Asmaa

AU - Iñiguez, Alonso J.

AU - Lubrano Di Ricco, Martina

AU - Manfredo Vieira, Silvio

AU - Ruff, William E.

AU - Mubiru, Derek

AU - Fine, Rebecca L.

AU - Sterpka, John

AU - Greiling, Teri M.

AU - Dehner, Carina

AU - Kriegel, Martin A.

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N2 - 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.

AB - 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.

KW - Clostridiaceae

KW - Clostridiales

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KW - Lactobacillus reuteri

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KW - human SLE microbiome

KW - interferon

KW - plasmacytoid dendritic cells

KW - resistant starch

KW - systemic lupus erythematosus

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

Abstract

Keywords

ASJC Scopus subject areas

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