The dietary source of trimethylamine N-oxide and clinical outcomes: an unexpected liaison

The profile of gut microbiota can vary according to host genetic and dietary characteristics, and be influenced by disease state and environmental stressors. The uremic dysbiosis results in a loss of biodiversity and overgrowth of microorganisms that may cause elevation of metabolic solutes such as trimethylamine N-oxide (TMAO), inducing pathogenic effects on its host. In patients with chronic kidney disease (CKD), TMAO levels are elevated because of a decreased clearance and an increased production from the uremic gut dysbiosis with a disrupted intestinal barrier and elevated enzymatic hepatic activity. Dietary precursors of TMAO are abundant in animal-derived foods such as red meat, egg yolk and other full-fat dietary products. TMAO is also found naturally in fish and certain types of seafood, with the TMAO content highly variable according to the depth of the sea where the fish is caught, as well as processing and storage. Although evidence points towards TMAO as being an important link to vascular damage and adverse cardiovascular outcomes, the evidence in CKD patients has not been consistent. In this review we discuss the potential dietary sources of TMAO and its actions on the intestinal microbiome as an explanation for the divergent results. We further highlight the potential of a healthy diet as one feasible therapeutic opportunity to prevent gut dysbiosis and reduce uremic toxin levels in patients with CKD. Lay Summary There is a link between the intestinal microbiota and human health. Patients with chronic kidney disease have an altered microbiota, with accumulation (because of decreased renal clearance) and increased production of toxins such as trimethylamine-N-oxide (TMAO). Elevated TMAO may induce cardiovascular and kidney damage. Dietary precursors of TMAO are found in animal-derived foods (red meat, egg, fish) and full-fat dietary products. In this review we discuss the potential dietary sources of TMAO, and its actions on the intestinal microbiome and association with worse clinical outcomes. We further highlight the potential of a healthy diet as one feasible therapeutic opportunity to prevent dysbiosis and reduce toxin levels in patients with chronic kidney disease.