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Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer III

ABSTRACT: Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer III

PROVIDER: PRJNA831823 | ENA |

REPOSITORIES: ENA

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Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer III

Project description:Epidemiological studies have indicated an association between statin use and reduced incidence of colorectal cancer (CRC), and work in preclinical models has demonstrated a potential chemopreventive effect. Statins are also associated with reduced dysbiosis in the gut microbiome, yet the role of the gut microbiome in the protective effect of statins in CRC is unclear. Here we validated the chemopreventive role of statins by retrospectively analysing a cohort of patients who underwent colonoscopies. This was confirmed in preclinical models and patient cohorts, and we found that reduced tumour burden was partly due to statin modulation of the gut microbiota. Specifically, the gut commensal Lactobacillus reuteri was increased as a result of increased microbial tryptophan availability in the gut after atorvastatin treatment. Our in vivo studies further revealed that L. reuteri administration suppressed colorectal tumorigenesis via the tryptophan catabolite, indole-3-lactic acid (ILA). ILA exerted anti-tumorigenic effects by downregulating the IL-17 signalling pathway. This microbial metabolite inhibited T helper 17 cell differentiation by targeting the nuclear receptor, RAR-related orphan receptor γt (RORγt). Together, our study provides insights into an anti-cancer mechanism driven by statin use and suggests that interventions with L. reuteri or ILA could complement chemoprevention strategies for CRC.

2023-02-17 | GSE201452 | GEO

Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer II

2023-02-17 | GSE201449 | GEO

Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer I

2023-02-17 | GSE201448 | GEO

Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer

Project description:Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer

| PRJNA831814 | ENA

Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer II

Project description:Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer II

| PRJNA831811 | ENA

Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer I

Project description:Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer I

| PRJNA831812 | ENA

Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-02-15 | GSE201453 | GEO

Proteomic characterization of the cellular effects of AHR activation by microbial tryptophan catabolites in endotoxin-activated human macrophages

Project description:Sensing of microbial tryptophan catabolites by the aryl hydrocarbon receptor (AhR) plays a pivotal role in host-microbiome homeostasis by modulating the host immune response. Thereby the involved cellular processes triggered by the metabolites are largely unknown. We analyzed proteomic changes in macrophages trough 24h after treatment with the tryptophan metabolites indole-3-acetic acid (I3AA) or indole-3-aldehyde (IAld), as well as the prototypic AhR-ligand Benzo(a)pyrene (BaP) in the absence and presence of LPS to identify affected processes and pathways.

2021-11-03 | PXD025022 | Pride

Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways

Project description:Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways

| PRJNA637035 | ENA

Statins affect gene expression in pancreatic cancer

Project description:The statin family of cholesterol-lowering drugs was shown to influence the risk of multiple types of cancers. However, the anti-tumor effects of statins in pancreatic cancer and their efficacy differs among the individual statins, are not currently well-defined. Thus, the aim of the present study was to identify the biological pathways affected by individual statins in human pancreatic cancer. The study was performed on human pancreatic cancer cell linesMiaPaCa-2 and PANC-1, exposed to three statins (Lovastatin, Fluvastatin and Simvastatin). mRNA-seq were performed (Sequenced with PE150, and 20M reads were generated.)

2020-04-30 | GSE149566 | GEO

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