Naturally- and anthropogenically-produced cresols could pose serious risks to fish health. In this study, three piscine CYP isoforms were investigated for their abilities to interact with p-cresol. Therefore, the activity of 7-ethoxyresorufin-O-deethylase (EROD), 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase (BFCOD), and p-nitrophenol hydroxylase (PNPH) were evaluated in the hepatic microsomes of juvenile rainbow trout. Results showed that EROD activity was inhibited in a competitive manner, BFCOD activity was inhibited in presence the highest tested p-cresol concentration and PNPH activity was not affected. These results indicate that p-cresol might affect the ability of fish to metabolize numerous aromatic hydrocarbons and dioxin compounds, which are present in the aquatic environment.
p-Cresol and indole are volatile biologically active products of the bacterial degradation of tyrosine and tryptophan respectively. They are typically produced by bacteria in animal intestines, soil and various sediments. Here, we demonstrate that the free-living eukaryote Mastigamoeba balamuthi and its pathogenic relative Entamoeba histolytica produce significant amounts of indole via tryptophanase activity. Unexpectedly, M. balamuthi also produces p-cresol in concentrations that are bacteriostatic to non-p-cresol-producing bacteria. The ability of M. balamuthi to produce p-cresol, which has not previously been observed in any eukaryotic microbe, was gained due to the lateral acquisition of a bacterial gene for 4-hydroxyphenylacetate decarboxylase (HPAD). In bacteria, the genes for HPAD and the S-adenosylmethionine-dependent activating enzyme (AE) are present in a common operon. In M. balamuthi, HPAD displays a unique fusion with the AE that suggests the operon-mediated transfer of genes from a bacterial donor. We also clarified that the tyrosine-to-4-hydroxyphenylacetate conversion proceeds via the Ehrlich pathway. The acquisition of the bacterial HPAD gene may provide M. balamuthi a competitive advantage over other microflora in its native habitat.
- MeSH
- Archamoebae genetics MeSH
- Bacteria genetics MeSH
- Genes, Bacterial * MeSH
- Indoles metabolism MeSH
- Carboxy-Lyases MeSH
- Cresols metabolism MeSH
- Operon MeSH
- Gene Transfer, Horizontal * MeSH
- S-Adenosylmethionine metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
Endophytic fungi are rich sources of structurally complex chemical scaffolds with interesting biological activities. However, their metabolome is still unknown, making them appealing for novel compound discovery. To maximize the number of secondary metabolites produced from a single microbial source, we used the "OSMAC (one strain-many compounds) approach." In potato dextrose medium, M. phaseolina produced phomeolic acid (1), ergosterol peroxide (2), and a volatile compound 1,4-benzene-diol. Incorporating an epigenetic modifier, sodium valproate, affected the metabolite profile of the fungus. It produced 3-acetyl-3-methyl dihydro-furan-2(3H)-one (3) and methyl-2-(methyl-thio)-butyrate (4), plus volatile chemicals: butylated hydroxy toluene (BHT), di-methyl-formamide, 3-amino-1-propanol, and 1,4-benzenediol, 2-amino-1-(O-methoxyphenyl) propane. The structure of compounds 1-4 was established with the help of spectroscopic data. This study revealed first-time compounds 1-4 in the fungus M. phaseolina using a classical and epigenetic manipulation approach.
- MeSH
- Ascomycota * metabolism MeSH
- Benzene metabolism MeSH
- Brugmansia * MeSH
- Butylated Hydroxytoluene metabolism MeSH
- Butyrates metabolism MeSH
- Endophytes chemistry MeSH
- Epigenesis, Genetic MeSH
- Formamides metabolism MeSH
- Furans metabolism MeSH
- Glucose metabolism MeSH
- Valproic Acid metabolism MeSH
- Propane metabolism MeSH
- Toluene metabolism MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Antioxidants pharmacology MeSH
- Biflavonoids pharmacology MeSH
- Butylated Hydroxytoluene pharmacology MeSH
- Rats MeSH
- Ascorbic Acid pharmacology MeSH
- Plants, Medicinal chemistry MeSH
- Cerebral Cortex metabolism drug effects MeSH
- In Vitro Techniques MeSH
- Iron metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
Background and Aim: Plant-based diets are associated with potential health benefits, but the contribution of gut microbiota remains to be clarified. We aimed to identify differences in key features of microbiome composition and function with relevance to metabolic health in individuals adhering to a vegan vs. omnivore diet. Methods: This cross-sectional study involved lean, healthy vegans (n = 62) and omnivore (n = 33) subjects. We assessed their glucose and lipid metabolism and employed an integrated multi-omics approach (16S rRNA sequencing, metabolomics profiling) to compare dietary intake, metabolic health, gut microbiome, and fecal, serum, and urine metabolomes. Results: The vegans had more favorable glucose and lipid homeostasis profiles than the omnivores. Long-term reported adherence to a vegan diet affected only 14.8% of all detected bacterial genera in fecal microbiome. However, significant differences in vegan and omnivore metabolomes were observed. In feces, 43.3% of all identified metabolites were significantly different between the vegans and omnivores, such as amino acid fermentation products p-cresol, scatole, indole, methional (lower in the vegans), and polysaccharide fermentation product short- and medium-chain fatty acids (SCFAs, MCFAs), and their derivatives (higher in the vegans). Vegan serum metabolome differed markedly from the omnivores (55.8% of all metabolites), especially in amino acid composition, such as low BCAAs, high SCFAs (formic-, acetic-, propionic-, butyric acids), and dimethylsulfone, the latter two being potential host microbiome co-metabolites. Using a machine-learning approach, we tested the discriminative power of each dataset. Best results were obtained for serum metabolome (accuracy rate 91.6%). Conclusion: While only small differences in the gut microbiota were found between the groups, their metabolic activity differed substantially. In particular, we observed a significantly different abundance of fermentation products associated with protein and carbohydrate intakes in the vegans. Vegans had significantly lower abundances of potentially harmful (such as p-cresol, lithocholic acid, BCAAs, aromatic compounds, etc.) and higher occurrence of potentially beneficial metabolites (SCFAs and their derivatives).
- Publication type
- Journal Article MeSH
- MeSH
- Adult MeSH
- Hippurates urine MeSH
- Cresols urine MeSH
- Rats MeSH
- Humans MeSH
- Mixed Function Oxygenases metabolism MeSH
- Occupational Exposure MeSH
- Sparteine metabolism urine MeSH
- Cytochrome P-450 Enzyme System MeSH
- Toluene blood metabolism urine MeSH
- Animals MeSH
- Check Tag
- Adult MeSH
- Rats MeSH
- Humans MeSH
- Animals MeSH
