Study 1
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB17660 | ENA |
REPOSITORIES: ENA
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Project description:The molecular mechanisms by which dietary fruits and vegetables confer cardiometabolic benefits remain poorly understood. Historically, these beneficial properties have been attributed to the antioxidant activity of flavonoids. Here, we reveal that the host metabolic benefits associated with flavonoid consumption actually hinge on gut microbial metabolism. However, flavonoids are consumed in a largely glycosylated form, rendering them poorly available for small intestinal absorption and subjecting them to microbial metabolism in the colon. We show that a single gut microbial flavonoid catabolite is sufficient to reduce diet-induced cardiometabolic disease burden in mice. Dietary supplementation with elderberry extract attenuated obesity and continuous delivery of the catabolite 4-hydroxphenylacetic acid was sufficient to reverse hepatic steatosis. Analysis of human gut metagenomes revealed that under one percent contains a flavonol catabolic pathway, underscoring the rarity of this process. Our study will impact the design of dietary and probiotic interventions to complement traditional cardiometabolic treatment strategies.
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Project description:Analysis of the gut single cell and spacial sequencing after skin HA digestion as a model of skin inflammation
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Project description:Reprogramming in vivo using OCT4, SOX2, KLF4 and MYC (OSKM) triggers cell dedifferentiation, which is considered of relevance for tissue repair and regeneration. However, little is known about the metabolic requirements of this process. We found that antibiotic depletion of the gut microbiota abolished in vivo reprogramming. Analysis of bacterial metagenomes from stool samples of wild type (WT) and OSKM mice treated with doxycycline led us to identify vitamin B12 as a key factor for in vivo reprogramming, which is partly supplied by the microbiome. We report that B12 demand increases during reprogramming due to enhanced expression of enzymes in the methionine cycle, and supplementing B12 levels both in vitro and in vivo enhances the efficiency of OSKM reprogramming.
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Project description:Patients diagnosed with cutaneous and/or gastrointestinal aGvHD provide a unique opportunity to perform an in-depth comparison of activated human CD8+ T cells homing to the gut and skin, in some cases even within the same host, at the same time, acting as key players in the same human disease, and exerting their effector functions in these two tissue environments. This study aims at the identification of novel biomarkers associated with skin- and gut-homing CD8+ T cells in general, and CD8+ T cell markers possibly linked to CTL-mediated skin- and gut damage in aGvHD in particular.
2018-11-01 | GSE103569 | GEO
Project description:The human gut is inhabited by a complex ecosystem of microorganisms, encompassing bacteria, viruses, protozoa, and fungi. Recent research has illuminated the significance of the gut fungal microbiota (mycobiota) in shaping host immunity and influencing the onset and progression of various human diseases. While most investigations into gut microbiota have centered on bacteria, accumulating evidence has underscored the role of mycobiota in the development of inflammatory bowel diseases (IBD), including both ulcerative colitis (UC) and Crohn's disease (CD). In this study, we present the isolation of the live Malassezia globosa strains from the intestinal mucosa of UC patients for the first time. We provide a comprehensive analysis of the characteristics and virulence of this fungus. Malassezia, primarily known to inhabit human skin, prompted us to compare the genomes, transcriptomes, and virulence of M. globosa gut isolates with those of M. globosa strains isolated from the skin. This comparative analysis aimed to discern potential niche-specific adaptations of the fungus. Our findings reveal a striking disparity in the pathogenicity of M. globosa isolated from the gut compared to its skin counterpart. In a mouse model, gut-isolated M. globosa exhibited a more pronounced exacerbation of DSS-induced colitis and elevated production of inflammatory cytokines. Additionally, transcriptome analysis indicated that gut isolates of M. globosa display heightened sensitivity to normoxia compared to their skin-isolated counterparts, suggesting adaptation to the hypoxic conditions prevalent in the intestinal mucosal environment
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