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

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PubMed ID: 30581114

Imagen Publicación

Zegarra-Ruiz DF, El Beidaq A, Iñiguez AJ, Lubrano Di Ricco M, Manfredo Vieira S, Ruff WE, Mubiru D, Fine RL, Sterpka J, Greiling TM, Dehner C, Kriegel MA

Cell Host Microbe. 01 2019

COMMENT: This paper is focused in the analysis of the influence of gut microbiome in autoimmunity, specifically in the Systemic Lupus Erythematosus (SLE) pathogenesis and evolution. As in many other pathologies related with gut-microbiome, the impairment of gut barrier integrity appears to be crucial. The authors demonstrate that the translocation of Lactobacillus reuteri exacerbates TLR7-dependent lupus. Based on these findings the authors design a resistant starch (RS) rich diet that get to ameliorate SLE disease manifestations and improve lupus outcome in mouse models of lupus.

MAIN RESULTS:

We set out to test the role of diet and the microbiota in TLR7- dependent mouse models of lupus and dissect its mechanisms. Using antibiotics and germ-free (GF) mice, we demonstrate that gut microbiota depletion ameliorates the IFN pathway and autoimmunity in these models. 

In addition, we characterized the gut and tissue microbiota and identified specific bacterial taxa that were linked to lupus development and associated with human SLE microbiomes. The autoimmune phenotype was transferable via the gut microbiota and gavage of a single commensal identified by these studies, Lactobacillus reuteri, drove the pathogenesis in the gnotobiotic setting. Finally, using RS as a dietary approach to modulate autoimmunity via the gut microbiota, we demonstrate that RS prevented IFN pathways, disease manifestations, and mortality in these models. L. reuteri abundance was inhibited by RS in vivo and its growth by SCFAs in vitro and in vivo, thus providing a mechanistic link between diet, the microbiota, and its effects on an autoimmune host 

CONCLUSIONS:

In summary, the current study highlights the relevance of diet-microbiota-host interactions in the development of autoimmunity and defines a link between pathobiont outgrowth and disease manifestations. Mechanistically, the pathobiont instigates the pDC-IFN axis in lupus-prone animals with excessive TLR7 signaling that results in impaired gut barrier integrity.

Contributor

Raquel Tobes