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- W4311447780 abstract "Abstract Background: The interaction between gut microbiota and innate immunity plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Myeloid differentiation factor 88 (MyD88) is the core adaptor for Toll-like receptors (TLRs) defending against microbial invasion and initiating downstream immune response during microbiota-host interaction. However, the role of MyD88 in the pathogenesis of IBD is controversial. This study aims to investigate the impact of MyD88 on intestinal inflammation and the underlying mechanism. Methods: MyD88 inhibitor (TJ-M2010-5, TJ5) were used to investigate the effect of MyD88 suppression on acute DSS-induced colitis. Disease activity index, colon length, histological score and inflammatory cytokines were examined to evaluate the colitis severity. The RNA transcriptome analysis and 16S rDNA sequencing were used to detect the potential mechanism. Results: In the acute DSS-colitis model, the colitis severity was not alleviated in TJ5-treated mice, though the significantly lower of MyD88 expression and NF-κB activation were exhibited compared with control mice. Meanwhile, the 16S rDNA sequencing and RNA transcriptome analysis showed a higher abundance of intestinal Proteobacteria and an up-regulation of NOD-like receptors (NLRs) signaling pathway in colitis mice after MyD88 suppression. Further blockade of the NLR signaling pathway or elimination of gut microbiota with broad-spectrum antibiotics in DSS-induced colitis mice treated with TJ5 ameliorated the disease severity that was not improved by solely MyD88 inhibition. The downregulated NLR signaling pathway after broad-spectrum antibiotics treatment suggested that the MyD88 suppressionassociated dysbiosis may stimulate intestinal inflammation via NLR signaling pathway. Conclusion: Our study revealed that the suppression of MyD88 may be associated with unfavorable changes in the gut microbiota composition and lead to immune activation mediated by NLRs, which may play an important role in modulating intestinal inflammation." @default.
- W4311447780 created "2022-12-26" @default.
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- W4311447780 date "2022-12-14" @default.
- W4311447780 modified "2023-10-17" @default.
- W4311447780 title "Suppression of MyD88 disturbs gut microbiota and activates NLRs pathway hence fails to ameliorate DSS-induced colitis" @default.
- W4311447780 doi "https://doi.org/10.21203/rs.3.rs-2361141/v1" @default.
- W4311447780 hasPublicationYear "2022" @default.
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