Dietary tyramine promotes colon cancer risk and development via increased DNA damage and enhanced inflammation [ApcMin/+]
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ABSTRACT: High consumption of dietary red or processed meat and fat are linked to increased risk of colorectal cancer (CRC). A number of potential mechanisms have been reported, such as the presence of dietary carcinogenic compounds, and elevated gut microbial degradation of proteins and glycoproteins. Tyramine is a commonly found biogenic amine in processed food and can also be produced by the gut microbiota from the dietary amino acid tyrosine. The role of tyramine in intestinal mucosal health and CRC tumorigenesis has not been well studied. Therefore, we used the human colorectal HCT116 cell line and the ApcMin/+ mouse model to investigate the role of tyramine in CRC.
Project description:High dietary consumption of red or processed meat is associated with increased risk of colorectal cancer (CRC), likely through the presence of dietary carcinogens. Tyramine is a biogenic amine commonly found in processed food and can be produced by the gut bacteria from tyrosine. However, the role of tyramine in intestinal mucosal health has not been studied. Therefore, we used the human colonic HCT116 cell line to investigate the role of tyramine in modulating CRC risk and development
Project description:The goal of this study is to compare the RNA expression profile of wild-type C. elegans nematodes to mutants defective in the synthesis of the biogenic amine neurotransmitters dopamine, serotonin, tyramine, and octopamine in day 2 adults.
Project description:Previously we reported that Salmonella can proliferate by deriving energy from two metabolites that naturally occur in the host as gut microbial metabolic byproducts, namely, tyramine (TYR, an aromatic amine) and D-glucuronic acid (DGA, a hexuronic acid). Salmonella Pathogenicity Island 13 (SPI-13) plays a critical role in the ability of Salmonella to derive energy from TYR and DGA, however the catabolism of these two micronutrients in Salmonella are poorly defined. The objective of this study was to identify the specific genetic components and the regulatory circuits for the construction of the TYR and DGA catabolic pathways in Salmonella. To accomplish this, we employed TYR and DGA-induced global transcriptional profiling and gene functional network analysis.
Project description:Colorectal cancer (CRC) is closely related to gut dysbiosis. We investigated the effects of imbalanced gut microbiota on the progression of intestinal adenoma in Apcmin/+ mice model using fecal microbiota transplantation (FMT). Administration of feces from CRC patients increased tumor proliferation and decreased apoptosis in tumor cells. Abnormal expression of genes related to Wnt-protein binding and lipid metabolic process was observed.
Project description:Inflammatory bowel disease (IBD) is characterized by dysbiosis of the gut microbiota and dysfunction of in testinal stem cells (ISCs). However, the direct interactions between IBD microbial factors and ISCs are unde scribed. Here, we identify α2A-adrenergic receptor (ADRA2A) as a highly expressed GPCR in ISCs. Through PRESTO-Tango screening, we demonstrate that tyramine, primarily produced by Enterococcus via tyrosine decarboxylase (tyrDC), serves as a microbial ligand for ADRA2A. Using an engineered tyrDC deficient Enterococcus faecalis strain and intestinal epithelial cell-specific Adra2a knockout mice, we show that Enterococcus-derived tyramine suppresses ISC proliferation, thereby impairing epithelial regeneration and exacerbating DSS-induced colitis through ADRA2A. Importantly, blocking the axis with an ADRA2A antagonist, yohimbine, disrupts tyramine-mediated suppression on ISCs and alleviates colitis.Our findings highlight a microbial ligand-GPCR pair in ISCs, revealing a causal link between microbial regulation of ISCs and colitis exacerbation and yielding a targeted therapeutic approach to restore ISC function in colitis.
Project description:Biogenic amine-producing bacteria are responsible for the production of basic nitrogenous compounds, such as histamine, cadaverine, tyramine and putrescine, after foods spoil due to microorganisms. In the present work, we applied a shotgun proteomics approach to quickly and easily characterize 15 different foodborne strains of biogenic amine-producing bacteria. A total of 10673 peptide spectrum matches (PSMs) belonging to 4081 nonredundant peptides and corresponding to 1811 annotated proteins were identified. With the results, relevant functional pathways were determined and the strains were differentiated into different Euclidean hierarchical clusters. Moreover, a predicted protein‒protein interaction network of biogenic amine foodborne strains was created. The whole confidence network contains 260 nodes and 1973 interactions. Most of the identified proteins were related to pathways and networks of energy, putrescine metabolism and host‒virus interaction. In addition, a total of 556 nonredundant peptides were identified as virulence factors, and most of these peptides corresponded to functions such as toxins, antimicrobial compound production, antimicrobial resistance, additional resistances and tolerances, host colonization and immune evasion, ABC transporters, phage proteins, and alternative virulence factors and proteins involved in horizontal transfer. Potential species-specific peptide biomarkers were screened. Thus, 77 species-specific peptide biomarkers belonging to 64 different proteins were proposed to identify 10 species (Enterobacter aerogenes, Enterobacter cloacae, Hafnia alvei, Klebsiella oxytoca, Morganella morganii, Proteus mirabilis, Proteus penneri, Proteus vulgaris, Raoutella planticola, Stenotrophomonas maltophilia). All of these results constitute the first major dataset of peptides and proteins of seafood biogenic amine-producing strains. This repository may be useful for further studies, for the development of new therapeutic treatments for food intoxication and for tracking microbial sources in foodstuffs.
Project description:The goal of this project was to understand the functional consequences of plasma biogenic amine serotonin (5-HT) elevation in megakaryocytes by measuring gene expression
Project description:The goal of this project was to understand the functional consequences of plasma biogenic amine serotonin (5-HT) elevation in megakaryocytes by measuring gene expression Total RNA was extracted from the megakaryocytes of mice treated with either 5-HT or saline and global gene expression was measured.
Project description:We identified certain members of the gut microbiota associated with a lower tumor burden in mouse models of colorectal cancer (CRC). Orally applied, a mix of four Clostridiales strains (CC4) prevented and even successfully treated CRC as a stand-alone therapy.