Determining effects of microbial metabolite, Urolithin A on colon epithelial cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA453152 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7059080.fastq.gz | Fastqsanger.gz | |||
| SRR7059081.fastq.gz | Fastqsanger.gz | |||
| SRR7059082.fastq.gz | Fastqsanger.gz | |||
| SRR7059083.fastq.gz | Fastqsanger.gz | |||
| SRR7059084.fastq.gz | Fastqsanger.gz |
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Project description:Numerous studies signify that diets rich in phytochemicals reduce the risk of inflammatory bowel diseases (IBDs). However, their effects are often not uniform among individuals, possibly due to inter-individual variation in gut microbiota. The host indigenous gut microbiota and their metabolites have emerged as factors that greatly influence the efficacy of dietary interventions. The biological activities, mechanisms of actions and the specific targets of several microbial metabolites are unknown. Urolithin A (UroA) is one such natural microbial metabolite, which showed (including our recent study) anti-carcinogenic, anti-oxidative and anti-inflammatory activities. The goal of the experiment to determine if Urolithin A blocks the genes induced by lipopolysaccharide (mimicking bacterial effects on colon) as well as determine effects of Urolithin A alone.
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Project description:Briefly, this is a 28-day dietary intervention study participants will be asked to eat 2 ounces (52 grams) of walnuts every day for 3 weeks, and at the end of the study period they will come in for a colonoscopy. Participants will first start a 1-week run-in period where they will be asked to avoid foods high in ellagic acid. In addition, they will be asked to complete food surveys and two sets of 3-day dietary records, and to provide colon biopsies for this study during their routine colonoscopy, as well as a blood, and two urine and stool samples. Urine samples will be used for analysis of urolithin, ellagic acid metabolites. Stool samples will be used to assess gut microbiota changes after walnut consumption. Dietary records will be used for compliance and Food Frequency Questionnaire will be used to assess dietary habits. Lastly, the biopsy samples will be used for analysis of biomarkers and anti-inflammatory in the colon, as well as adherent microbiome to the colonic tissue. Data will be analyzed based on the urolithin phenotypes.
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Project description:To investigate the effect of Uroltihin A on T cell differentiation and gene expression, we treated purified CD3+ cells with DMSO or Urolithin A
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Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with learning, memory, and cognitive deficits. Neuroinflammation and lysosomal dysfunction are thought to play key roles in the progression of AD pathology. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Urolithin A (UA) is a gut microbial metabolite of ellagic acid shown to stimulate mitophagy and acts as a potent anti-inflammatory and anti-oxidant agent. However, long-term safety and the potential role of UA in altering pathology of AD is still largely unclear. In this study, we investigated the underlying mechanisms for the beneficial effects of UA in multiple mouse models of AD. We report that long-term UA treatment significantly improves learning and memory, olfactory function, and synaptic function of neurons in AD transgenic mice. We demonstrate that UA decreases soluble and insoluble Ab1-42, total Tau, and Tau phosphorylation. Furthermore, alterations in lysosomal cathepsins, particularly upregulation of cathepsin Z, was observed in the AD mice brains and normalized by UA treatment. Notably, UA treatment also ameliorates neuroinflammation, DNA damage, mitochondrial dysfunction, and restores lysosomal functions in AD mice brains. Collectively, these results provide new insights into the role of UA in regulating lysosomal dysfunction, cathepsins, and suggests that UA may have a potential therapeutic application for AD. To understand what metabolism-related gene expression changes are induced by Urolithin A, WT (C57BL6/J), 3xTgAD and 3xTgAD/PolB+/- mice were treated with water or Urolithin A (200mg/kg/day) by oral gavage for 5 months starting when the mice were 12m of age, thereafter hippocampi tissues was collected from each mouse and subjected to RNA isolation.
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Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with learning, memory, and cognitive deficits. Neuroinflammation and lysosomal dysfunction are thought to play key roles in the progression of AD pathology. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Urolithin A (UA) is a gut microbial metabolite of ellagic acid shown to stimulate mitophagy and acts as a potent anti-inflammatory and anti-oxidant agent. However, long-term safety and the potential role of UA in altering pathology of AD is still largely unclear. In this study, we investigated the underlying mechanisms for the beneficial effects of UA in multiple mouse models of AD. We report that long-term UA treatment significantly improves learning and memory, olfactory function, and synaptic function of neurons in AD transgenic mice. We demonstrate that UA decreases soluble and insoluble Ab1-42, total Tau, and Tau phosphorylation. Furthermore, alterations in lysosomal cathepsins, particularly upregulation of cathepsin Z, was observed in the AD mice brains and normalized by UA treatment. Notably, UA treatment also ameliorates neuroinflammation, DNA damage, mitochondrial dysfunction, and restores lysosomal functions in AD mice brains. Collectively, these results provide new insights into the role of UA in regulating lysosomal dysfunction, cathepsins, and suggests that UA may have a potential therapeutic application for AD. To understand what gene expression changes are induced by Urolithin A, WT (C57BL6/J), 3xTgAD and 3xTgAD/PolB+/- mice were treated with water or Urolithin A (200mg/kg/day) by oral gavage for 5 months starting when the mice were 12m of age. Thereafter, hippocampi tissue was collected from each mouse and subjected to RNA isolation.
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Project description:The identification of new agents that may modulate the progression of cancer cell growth is of great interest. In this regard, dietary agents can be utilized to identify molecular targets to be used as part of a chemopreventive strategy. Walnuts contain several bioactive compounds, including pedunculagin, a polyphenol metabolized by microbiota to form urolithins, namely urolithin A (UA). We performed a genomic analysis to study the effect of UA on androgen-dependent LNCaP prostate adenocarcinoma cells. Cells were incubated with 40µM UA for 24 hours, then, RNA was extracted. RNA samples were processed in the automated Biomek FX System (Beckman Coulter), where aRNA was produced, and labeled with Biotin, purified , fragmented and hybridized onto HG U219-24 Array, using the GeneChip HT 3âIVT Express Kit . Afterwards, the GeneTitan® Multi-Channel (MC) Instrument (Affymetrix) was used to hybridize, wash , stain , and scan the arrays. Microarray results were analyzed using the GeneSpring GX v13.0 software. LNCaP cells were plated in 35mm wells, the following day they were treated with 40µM urolithin A (UA) for 24 hours, after incubation Total RNA was extracted using Qiagen RNAeasy minikit. The Affymetrix Human Genome U219 array plate was used, which measures gene expression of more than 36 000 transcripts and variants per sample, which represent more than 20 000 genes.
2016-07-27 | E-GEOD-65527 | biostudies-arrayexpress