Influence of Proteus sp. on Trimethylamine N- Oxide production via the Choline Metabolism Pathway and the Formulation of a Predictive Model to Assess the Risk of Coronary Artery Disease in Indian Patients

Abstract

Background and Aim: Proteus bacteria, a key contributor to several gastrointestinal diseases, is known to survive in the wide pH range offered by different locations of the GI tract. The bacterial enzyme Choline TMA Lyase found in several opportunistic gut commensals catalyzes choline conversion to trimethylamine, a precursor of the pro-atherosclerotic metabolite trimethylamine N oxide. This study evaluates the pathogenic potential of Proteus gut bacteria in patients with coronary artery disease. We also sought to create a simple predictive model for assessing risk factors of coronary artery disease using a sample of Indian patients. Materials and Methods: The study included 14 patients with coronary artery disease and 6 controls. Optimal conditions were devised, and standardized protocols were followed to culture Proteus bacteria in vitro and isolate the protein of interest, Choline TMA Lyase. FTIR analysis and UV spectrophotometry were employed to quantify choline and trimethylamine N oxide levels, respectively. Finally, receiver operating characteristic analysis and multivariate logistic regression established the predictive power of the entire model and trimethylamine N oxide. Results: The findings demonstrated an optimum activity of this protein and the bacterial growth in the pH range of 7.4 - 9. Quantitative analysis showed trimethylamine N oxide levels to be significantly higher in coronary artery disease patients (1.81 µM) than in controls (0.86 µM). Conclusion: Optimum activity in the alkaline condition indicates the strong pathological potential of Proteus bacteria in the progression of coronary artery disease. The prediction model can serve as a helpful tool within the medical community to assess the risk factors for coronary artery disease. et al. Influence of Proteus spp. on Trimethylamine N- Oxide production via the Choline Metabolism Pathway and the Formulation of a Predictive