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Atorvastatin improved ulcerative colitis in association with gut microbiota-derived tryptophan metabolism

ABSTRACT: Atorvastatin improved ulcerative colitis in association with gut microbiota-derived tryptophan metabolism

PROVIDER: PRJNA1181541 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31208800_1.fastq.gz	Fastqsanger.gz
	SRR31208800_2.fastq.gz	Fastqsanger.gz
	SRR31208801_1.fastq.gz	Fastqsanger.gz
	SRR31208801_2.fastq.gz	Fastqsanger.gz
	SRR31208802_1.fastq.gz	Fastqsanger.gz

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Atorvastatin improved ulcerative colitis in association with gut microbiota-derived tryptophan metabolism

Project description:Aims: Atorvastatin is a commonly used cholesterol-lowering drug that possesses non-canonical anti-inflammatory properties. However, the precise mechanism underlying its anti-inflammatory effects remains unclear. Materials and methods: The acute phase of ulcerative colitis (UC) was induced using a 5 % dextran sulfate sodium (DSS) solution for 7 consecutive days and administrated with atorvastatin (10 mg/kg) from day 3 to day 7. mRNA-seq, histological pathology, and inflammatory response were determined. Intestinal microbiota alteration, tryptophan, and its metabolites were analyzed through 16S rRNA sequencing and untargeted metabolomics. Key findings: Atorvastatin relieved the DSS-induced UC in mice, as evidenced by colon length, body weight, disease activity index score and pathological staining. Atorvastatin treatment reduced the level of pro_x0002_inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Atorvastatin also relieved the intestinal microbiota disorder caused by UC and decreased the proliferation of pernicious microbiota such as Akkermansia and Bacteroides. Atorvastatin dramatically altered tryptophan metabolism and increased the fecal contents of tryptophan, indolelactic acid (ILA), and indole-3-acetic acid (IAA). Furthermore, atorvastatin enhanced the expression level of aryl hydrocarbon receptor (AhR) and interleukin-22 (IL-22) and further promoted the expression level of intestinal tight junction proteins, such as ZO-1 and occludin, in colitis mice. Significance: These findings indicated that atorvastatin could alleviate UC by regulating intestinal flora disorders, promoting microbial tryptophan metabolism, and repairing the intestinal barrier.

2024-11-04 | GSE280960 | GEO

Testing Atorvastatin to Lower Colon Cancer Risk in Longstanding Ulcerative Colitis

Project description:This phase II trial studies the effect of atorvastatin in treating patients with ulcerative colitis who have a dominant-negative missense P53 mutation and are at risk of developing large intestinal cancer. Patients with ulcerative colitis are known to have an increased risk of developing large intestinal cancer. Better ways to control ulcerative colitis and more knowledge about how to prevent colon cancer are needed. Atorvastatin is a drug used to lower the amount of cholesterol in the blood and to prevent stroke, heart attack, and angina (chest pain). It blocks an enzyme that helps make cholesterol in the body. It also causes an increase in the breakdown of cholesterol. The information gained from this study may help doctors learn more about atorvastatin as an agent in cancer prevention, and may help to improve public health.

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Ulcerative colitis gene expressions file

Project description:Ulcerative colitis related gene expressions analysis in colonic biopsy samples from control and ulcerative colitis patients

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Methylation profiling in Ulcerative colitis

Project description:The series was designed to identify the different methylated single CpGs involved in the pathophysiology of ulcerative colitis. A cohort of n=20 monozygotic twins, discordant for ulcerative colitis was selected. Illumina and Nimblegen platforms were used.

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