Determining effects of microbial metabolite, Urolithin A on colon epithelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE113581 | GEO | 2019/10/07
REPOSITORIES: GEO
Similar Datasets
Project description:Gut microbiota is an unignored target in maintaining intestinal homeostasis due to its regulatory effects on intestinal health through multiple mechanisms, including enhancing intestinal barriers, modulating microbial diversity, secreting various metabolites, etc. Bacteriocins produced by probiotics have been gradually proved vital for intestinal diseases intervention, however, the corresponding mechanisms have received less attention and the whole story of their regulative activities are hard to be fully uncovered. The two-peptide Plantaricin NC8 (PLNC8), coded by gene plnc8, is a bacteriocin ubiquitously produced by Lactobacillus plantarum, has been regarded as the potential vital bacteriocin for the anti-inflammatory effects of Lactobacillus plantarum. This study exploited CRISPR-cas9 and prokaryotic gene overexpression techniques to construct the plnc8 strains for the anti-inflammatory mechanism investigation. Based on the metagenomics, transcriptomics and metabolomics analysis, the anti-enteritis mechanism of PLNC8 systematically in DSS-induced enteritis models were comprehensively revealed. PLNC8 induced alterations in the composition of gut microbiota composition, promoting the alterations of multiple probiotics such as Eubacterium plexicaudatum, Doreasp.5-2, Enterococcus cecorum and Prevotella oulorum. Besides, various metabolites produced by the gut microbiota were influenced, and the key metabolites of xanthine, hypoxanthine, and L-histidine were regulated via purine and histidine metabolic pathways. These metabolites further inhibited p38 MAPK phosphorylation of enterocytes induced by DSS. Ultimately, the intestinal barrier repairment and anti- enteritis were achieved, proving the anti-enteritis effects of PLNC8 via microbe-metabolites-enterocyte axis.
2024-08-20 | GSE274981 | GEO
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.
2024-07-01 | GSE214416 | GEO
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.
2024-07-01 | GSE214406 | GEO
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.
| 2314530 | ecrin-mdr-crc
Project description:Recent studies in both mice and human have suggested that the gut microbiota could modulate tumor response to chemotherapeutic agents or immunotherapies. However, the underlying mechanism has not been well characterized. Here, we found that disruption of the intestinal microbiota with antibiotics impaired the anti-cancer efficacy of oxaliplatin, which was correlated with the reduction of lots of the intestinal microbial metabolites including butyrate, one of the short chain fatty acids. Re-supplementation of either the whole intestinal microbial metabolites or butyrate could rescue the therapeutic responses of oxaliplatin in the microbiota-destroyed tumor-bearing mice by modulating CD8+ T cell function in the tumor microenvironment. Further experiments showed butyrate boosted the anti-tumor cytotoxic CD8+ T cell responses through ID2, a key transcription regulator highly expressed by tumor-infiltrating CD8+ T cells. Butyrate induced ID2 expression in CD8+ T cells, while ID2 further promoted the proliferation and function of CD8+ T cells through IL-12 signaling. Together, our findings suggest that gut microbial metabolite butyrate could promote the anti-tumor therapeutic efficacy through the ID2-dependent regulation of CD8+ T cell immunity.
2021-03-24 | GSE115283 | GEO
Project description:Recent studies in both mice and human have suggested that the gut microbiota could modulate tumor response to chemotherapeutic agents or immunotherapies. However, the underlying mechanism has not been well characterized. Here, we found that disruption of the intestinal microbiota with antibiotics impaired the anti-cancer efficacy of oxaliplatin, which was correlated with the reduction of lots of the intestinal microbial metabolites including butyrate, one of the short chain fatty acids. Re-supplementation of either the whole intestinal microbial metabolites or butyrate could rescue the therapeutic responses of oxaliplatin in the microbiota-destroyed tumor-bearing mice by modulating CD8+ T cell function in the tumor microenvironment. Further experiments showed butyrate boosted the anti-tumor cytotoxic CD8+ T cell responses through ID2, a key transcription regulator highly expressed by tumor-infiltrating CD8+ T cells. Butyrate induced ID2 expression in CD8+ T cells, while ID2 further promoted the proliferation and function of CD8+ T cells through IL-12 signaling. Together, our findings suggest that gut microbial metabolite butyrate could promote the anti-tumor therapeutic efficacy through the ID2-dependent regulation of CD8+ T cell immunity.
2021-03-24 | GSE115426 | GEO
Project description:To investigate the effects of ppIAPP-GFP expression and urolithin B treatment in the gene expression of Saccharomyces cerevisiae cells, we compared different cells: cells expressing the empty vector, cells expressing ppIAPP-GFP, cells expressing the empty vector treated with urolithin B, cells expressing ppIAPP-GFP treated with urolithin B
2022-11-24 | GSE218152 | GEO
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
Project description:The effect of oral microbiota on the intestinal microbiota has garnered growing attention as a mechanism linking periodontal diseases to systemic diseases. However, the salivary microbiota is diverse and comprises numerous bacteria with a largely similar composition in healthy individuals and periodontitis patients. Thus, the systemic effects of small differences in the oral microbiota are unclear. In this study, we explored how health-associated and periodontitis-associated salivary microbiota differently colonized the intestine and their subsequent systemic effects by analyzing the hepatic gene expression and serum metabolomic profiles. The salivary microbiota was collected from a healthy individual and a periodontitis patient and gavaged into C57BL/6NJcl[GF] mice. Samples were collected five weeks after administration. Gut microbial communities were analyzed by 16S ribosomal RNA gene sequencing. Hepatic gene expression profiles were analyzed using a DNA microarray and quantitative polymerase chain reaction. Serum metabolites were analyzed by capillary electrophoresis time-of-flight mass spectrometry. The gut microbial composition at the genus level was significantly different between periodontitis-associated microbiota-administered (PAO) and health-associated oral microbiota-administered (HAO) mice. The hepatic gene expression profile demonstrated a distinct pattern between the two groups, with higher expression of Neat1, Mt1, Mt2, and Spindlin1, which are involved in lipid and glucose metabolism. Disease-associated metabolites such as 2-hydroxyisobutyric acid and hydroxybenzoic acid were elevated in PAO mice. These metabolites were significantly correlated with Bifidobacterium, Atomobium, Campylobacter, and Haemophilus, which are characteristic taxa in PAO mice. Conversely, health-associated oral microbiota were associated with higher levels of beneficial serum metabolites in HAO mice. The multi-omics approach used in this study revealed that periodontitis-associated oral microbiota is associated with the induction of disease phenotype when they colonized the gut of germ-free mice.
2022-08-17 | GSE198570 | GEO
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.
2024-07-01 | GSE212972 | GEO