Clinical and experimental rheumatology · 2026
Gut microbiota dysbiosis exacerbates microscopic polyangiitis via toll-like receptor 7.
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Yang Binglan, Chu Liepeng, Lu Shurong, Tang Wenglv, Xue Chao
Аннотация
OBJECTIVES: Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is closely associated with factors such as genetic predisposition, environmental pollution, medications, and infections. Some bacteria have been definitively linked to AAV. Although gut microbiota dysbiosis has been confirmed in individuals with AAV, the specific role of this dysbiosis and the associated mechanisms contributing to AAV pathogenesis remain unexplored. The most common type of AAV in China is microscopic polyangiitis (MPA).
METHODS: We used propylthiouracil/phorbol 12-myristate 13-acetate (PMA/PTU) to establish a rat model of MPA. We then administered ceftriaxone sodium to induce dysbiosis of the rat intestinal microflora. We determined differences in gut microbiota using 16sRNA analysis, the degree of kidney and lung injury in rats using haematoxylin-eosin staining, the level of inflammatory factors in peripheral blood using an enzyme-linked immunosorbent assay, the distribution of splenic lymphocyte subpopulations using flow cytometry, the expression of Toll-like receptor 7 (TLR7) in the colon using Western blotting, and the release of neutrophil extracellular traps (NETs) from kidneys using immunofluorescence to assess the impact of gut dysbiosis on MPA.
RESULTS: The results showed that the MPA rat model displayed characteristics consistent with those of human MPA patients. The gut microbiota in rats in the gut dysbiosis group significantly differed from that in rats in the MPA group. Gut microbiota dysbiosis triggered increased release of renal NETs through activation of TLR7 protein, exacerbated microinflammation, increased peripheral blood Interleukin-1β, interleukin-6, C-reactive protein, and tumour necrosis factor-α, disrupted immune homeostasis, and increased the number of CD4+ T cells, CD8+ T cells, and Th17 cells through TLR7 signalling.
CONCLUSIONS: Our findings show that microbiota dysbiosis led to increased release of NETs, more severe microinflammation, disruption of immune homeostasis, and exacerbated organ damage in the kidneys of MPA rats through activation of TLR7.
METHODS: We used propylthiouracil/phorbol 12-myristate 13-acetate (PMA/PTU) to establish a rat model of MPA. We then administered ceftriaxone sodium to induce dysbiosis of the rat intestinal microflora. We determined differences in gut microbiota using 16sRNA analysis, the degree of kidney and lung injury in rats using haematoxylin-eosin staining, the level of inflammatory factors in peripheral blood using an enzyme-linked immunosorbent assay, the distribution of splenic lymphocyte subpopulations using flow cytometry, the expression of Toll-like receptor 7 (TLR7) in the colon using Western blotting, and the release of neutrophil extracellular traps (NETs) from kidneys using immunofluorescence to assess the impact of gut dysbiosis on MPA.
RESULTS: The results showed that the MPA rat model displayed characteristics consistent with those of human MPA patients. The gut microbiota in rats in the gut dysbiosis group significantly differed from that in rats in the MPA group. Gut microbiota dysbiosis triggered increased release of renal NETs through activation of TLR7 protein, exacerbated microinflammation, increased peripheral blood Interleukin-1β, interleukin-6, C-reactive protein, and tumour necrosis factor-α, disrupted immune homeostasis, and increased the number of CD4+ T cells, CD8+ T cells, and Th17 cells through TLR7 signalling.
CONCLUSIONS: Our findings show that microbiota dysbiosis led to increased release of NETs, more severe microinflammation, disruption of immune homeostasis, and exacerbated organ damage in the kidneys of MPA rats through activation of TLR7.