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.

Automated summary

The composition of gut microbiota can be influenced by host genetic and dietary characteristics, as well as disease state and environmental stressors. Uremic dysbiosis, characterized by a loss of biodiversity and overgrowth of microorganisms, can lead to the elevation of metabolic solutes such as TMAO, which may have pathogenic effects on the host. TMAO levels are elevated in patients with chronic kidney disease due to decreased clearance and increased production from uremic dysbiosis. Dietary precursors of TMAO can be found in animal-derived foods and certain types of seafood. Although TMAO has been linked to vascular damage and adverse cardiovascular outcomes, the evidence in CKD patients is inconsistent. This review explores the potential dietary sources of TMAO and its effects on the intestinal microbiome, as well as the role of a healthy diet in preventing dysbiosis and reducing toxin levels in CKD patients.