Originally posted by Pooka1
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2) This needs to replicated a few times for confirmation.
However they didn't simply show that a resistant starch diet ameliorated lupus. Although that would have been an interesting find it wouldn't necessarily explain the cause of the disease.
In this study the first thing they did was show that Lupus was a direct result of harmful stomach bacteria. After explaining the cause of the disease they modified its course with diet. That's what makes this stand out.
The Gut Microbiota Exacerbates Lupus-Related Mortality and Pathogenesis
The TLR7/IFN pathway is central in the pathogenesis of human SLE (Crow, 2014). Thus, we used a TLR7-dependent spontaneous and inducible mouse model to study the role of the microbiota in systemic autoimmunity. Lupus-prone TLR7.1 Tg C57BL/6 mice exhibit an 8- to 16-fold increase in TLR7 expression and spontaneously develop systemic signs of SLE starting at 6 weeks of age (Deane et al., 2007). To induce lupus-like disease in mice not genetically prone to excessive TLR7 signaling, we used topical imiquimod (IMQ), a TLR7 agonist, which was applied to the skin three times a week to 8-week-old wild-type (WT) C57BL/6 mice (Yokogawa et al., 2014). To assess the role of the gut microbiota, we suppressed its growth in both models using broad-spectrum antibiotics (ABX) or a GF state (Figure S1A). These interventions led to significantly increased survival (Figure 1A), decreased splenomegaly and hepatomegaly (Figure 1B), and decreased type I IFN gene expression in ileum and spleen as well as type I IFN secretion in the blood (Figures 1C and 1D). Consistent with systemic IFN levels, pDCs accumulated in spleen, mesenteric lymph nodes (MLN), and Peyer’s patches (PP) in both models and were also suppressed by antibiotics or a GF state (Figures 1E and 1F).
Blood disorders (anemia and leukocytosis) were normalized in antibiotic-treated mice and in the GF setting, suggesting that particularly these manifestations are microbiota dependent (Figure S1B). Antibiotics decreased bone marrow cellular depletion, and restored granulocyte-monocyte and megakaryocyte-erythrocyte progenitor populations (Figures S1C–S1E), thereby preventing IFN-dependent emergency myelopoiesis (Buechler et al., 2013). Finally, depletion of the gut microbiota decreased renal injury due to immune cell infiltration and nephritis (Figures 1G, 1H, and S1F) and improved renal physiology by decreasing proteinuria (Figure 1I).
These data indicate that the gut microbiota is needed for TLR7-dependent systemic autoimmunity. We next defined the gut microbial community structure in both models in order to identify potential pathobionts driving lupus pathogenesis.
The TLR7/IFN pathway is central in the pathogenesis of human SLE (Crow, 2014). Thus, we used a TLR7-dependent spontaneous and inducible mouse model to study the role of the microbiota in systemic autoimmunity. Lupus-prone TLR7.1 Tg C57BL/6 mice exhibit an 8- to 16-fold increase in TLR7 expression and spontaneously develop systemic signs of SLE starting at 6 weeks of age (Deane et al., 2007). To induce lupus-like disease in mice not genetically prone to excessive TLR7 signaling, we used topical imiquimod (IMQ), a TLR7 agonist, which was applied to the skin three times a week to 8-week-old wild-type (WT) C57BL/6 mice (Yokogawa et al., 2014). To assess the role of the gut microbiota, we suppressed its growth in both models using broad-spectrum antibiotics (ABX) or a GF state (Figure S1A). These interventions led to significantly increased survival (Figure 1A), decreased splenomegaly and hepatomegaly (Figure 1B), and decreased type I IFN gene expression in ileum and spleen as well as type I IFN secretion in the blood (Figures 1C and 1D). Consistent with systemic IFN levels, pDCs accumulated in spleen, mesenteric lymph nodes (MLN), and Peyer’s patches (PP) in both models and were also suppressed by antibiotics or a GF state (Figures 1E and 1F).
Blood disorders (anemia and leukocytosis) were normalized in antibiotic-treated mice and in the GF setting, suggesting that particularly these manifestations are microbiota dependent (Figure S1B). Antibiotics decreased bone marrow cellular depletion, and restored granulocyte-monocyte and megakaryocyte-erythrocyte progenitor populations (Figures S1C–S1E), thereby preventing IFN-dependent emergency myelopoiesis (Buechler et al., 2013). Finally, depletion of the gut microbiota decreased renal injury due to immune cell infiltration and nephritis (Figures 1G, 1H, and S1F) and improved renal physiology by decreasing proteinuria (Figure 1I).
These data indicate that the gut microbiota is needed for TLR7-dependent systemic autoimmunity. We next defined the gut microbial community structure in both models in order to identify potential pathobionts driving lupus pathogenesis.
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