Dataset Information

Alterations of the Gut Microbiota Associated With Promoting Efficacy of Prednisone by Bromofuranone in MRL/lpr Mice.

ABSTRACT: Gut microbiota played an important role in systemic lupus erythematosus (SLE) and glucocorticoids were prone to cause alterations in gut microbiota. This study addressed the effect of bromofuranone on the treatment of SLE with prednisone, since bromofuranone could regulate gut microbiota by inhibiting the AI-2/LuxS quorum-sensing. Remarkably, bromofuranone did not alleviate lupus but promoted the efficacy of prednisone in the treatment of lupus. The alterations in the gut microbiota, including decreased Mucispirillum, Oscillospira, Bilophila and Rikenella, and increased Anaerostipes, were associated with prednisone treatment for SLE. In addition, the increase of Lactobacillus, Allobaculum, Sutterella, and Adlercreutzia was positively associated with the bromofuranone-mediated promotion for the treatment of lupus. This was the first study demonstrating that the efficacy of glucocorticoids could be affected by the interventions in gut microbiota.

SUBMITTER: He Z

PROVIDER: S-EPMC6504707 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Alterations of the Gut Microbiota Associated With Promoting Efficacy of Prednisone by Bromofuranone in MRL/lpr Mice.

He Zhixing Z Kong Xiangyu X Shao Tiejuan T Zhang Yun Y Wen Chengping C

Frontiers in microbiology 20190501

Gut microbiota played an important role in systemic lupus erythematosus (SLE) and glucocorticoids were prone to cause alterations in gut microbiota. This study addressed the effect of bromofuranone on the treatment of SLE with prednisone, since bromofuranone could regulate gut microbiota by inhibiting the AI-2/LuxS quorum-sensing. Remarkably, bromofuranone did not alleviate lupus but promoted the efficacy of prednisone in the treatment of lupus. The alterations in the gut microbiota, including d ...[more]

PMID: 31118928

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Project description:Microbiome composition and function have been implicated as contributing factors in the pathogenesis of autoimmune diseases (ADs), including systemic lupus erythematosus (SLE), rheumatoid arthritis and autoimmune hepatitis (AIH). Furthermore, dysbiosis of gut microbiome is associated with impaired barrier function and mucosal immune dysregulation. However, mechanisms by which gut microbiome contributes to the ADs and whether antioxidant treatment can restore gut homeostasis and ameliorate the disease outcome are not known. This study was, therefore, focused on examining the involvement of gut microbiome and host responses in the pathogenesis of SLE using unique female mouse models (C57BL/6, MRL+/+ and MRL/lpr) of 6 and 18 weeks with varying degrees of disease progression. Fecal microbiome diversity and composition, gut oxidative stress (OS), barrier function and inflammation, as well as systemic autoimmunity were determined. Interestingly, each mouse strain had distinct bacterial community as revealed by β-diversity. A lower Firmicutes/Bacteroidetes ratio in 6-week-old MRL/lpr mice was observed, evidenced by decrease in Peptostreptococcaceae under Firmicutes phylum along with enrichment of Rikenellaceae under Bacteroidetes phylum. Additionally, we observed increases in colonic OS [4-hydroxynonenal (HNE)-adducts and HNE-specific immune complexes], permeability changes (lower tight junction protein ZO-2; increased fecal albumin and IgA levels) and inflammatory responses (increased phos-NF-κB, IL-6 and IgG levels) in 18-week-old MRL/lpr mice. These changes were associated with markedly elevated AD markers (antinuclear and anti-smooth muscle antibodies) along with hepatic portal inflammation and severe glomerulonephritis. Notably, antioxidant N-acetylcysteine treatment influenced the microbial composition (decreased Rikenellaceae; increased Akkeransiaceae, Erysipelotrichaceae and Muribaculaceae) and attenuated the systemic autoimmunity in MRL/lpr mice. Our data thus show that gut microbiome dysbiosis is associated with increased colonic OS, barrier dysfunction, inflammatory responses and systemic autoimmunity markers. These findings apart from delineating a role for gut microbiome dysbiosis, also support the contribution of gut OS, permeability changes and inflammatory responses in the pathogenesis of ADs.

Dataset Information

Alterations of the Gut Microbiota Associated With Promoting Efficacy of Prednisone by Bromofuranone in MRL/lpr Mice.

Publications

Alterations of the Gut Microbiota Associated With Promoting Efficacy of Prednisone by Bromofuranone in MRL/lpr Mice.

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