In Vitro Detoxification Studies of p-Cresol by Intestinal Bacteria Isolated from Human Feces.

Abstract

p-Cresol is a neurotoxic and nephrotoxic carcinogenic aromatic substance produced as a result of microbial fermentation in the intestine. The derivatives of p-cresol (p-cresyl sulphate or p-cresyl glucuronide) have a deleterious effect on renal failure patients undergoing hemodialysis. Human gut seems to be inhabited with a diverse microbial population capable of detoxifying many aromatic compounds. However, the knowledge on the role of gut microbes in metabolizing p-cresol is limited. Hence, the present study aims to investigate p-cresol detoxification by intestinal bacteria isolated from human feces. Three potential p-cresol tolerant isolates were selected and identified as Enterococcus faecalis strains (UTD-1, UTD-2 and UTD-3) by 16SrRNA gene sequencing. All three E. faecalis isolates decreased the p-cresol concentration (30µg/ml) at a higher rate with extracellular extracts (2.58-9.53µg/ml) as compared to intracellular (0.55-5.28µg/ml) extract. These three potential isolates also exhibited tolerance to gastrointestinal conditions for up to 60min. Added to its potential, the expression of virulent genes (esp, gelE, and cyl) was found to be suppressed when subjected to bile stress under in vitro conditions. HPLC analysis displayed transformed products from extracellular extract treated samples were comparable to the metabolite standard of the p-cresol degradation pathway. Infrared spectral analysis too showed the spectrum similarity with metabolite standard. Thus, conclusively, intestinal isolates E. faecalis (UTD-1, UTD-2 and UTD-3) might be a promising candidate for mitigating p-cresol detoxification in uremic patients.