The gut microbiota plays a pivotal role in the onset and development of diabetes and its complications. Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite of certain nutrients, is associated with type 2 diabetes and its complications. Diabetic kidney disease (DKD) is one of the most serious microvascular complications. However, whether TMAO accelerates the development of DKD remains unclear. We tested the hypothesis that TMAO accelerates the development of DKD. A high-fat diet/low-dose streptozotocin-induced diabetes rat model was established, with or without TMAO in the rats’ drinking water. Compared to the normal rats, the DKD rats showed significantly higher plasma TMAO levels at the end of the study. TMAO treatment not only exacerbated the kidney dysfunction of the DKD rats, but also renal fibrosis. Furthermore, TMAO treatment activated the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome and resulted in the release of interleukin (IL)-1β and IL-18 to accelerate renal inflammation. These results suggested that TMAO aggravated renal inflammation and fibrosis in the DKD rats, which provides a new perspective to understand the pathogenesis of DKD and a potential novel target for preventing the progression of DKD.

The gut microbiota and its metabolites have become a hotspot of recent research. Trimethylamine N-oxide (TMAO) metabolized by the gut microbiota is closely related to many diseases such as cardiovascular disease, chronic kidney disease, type 2 diabetes, etc. Chronic kidney disease (CKD) is an important contributor to morbidity and mortality from non-communicable diseases. Recently, increasing focus has been put on the role of TMAO in the development and progress of chronic kidney disease. The level of TMAO in patients with chronic kidney disease is significantly increased, and a high level of TMAO deteriorates chronic kidney disease. This article describes the relationship between TMAO and chronic kidney disease and the research progress of drugs targeted TMAO, providing a reference for the development of anti-chronic kidney disease drugs targeted TMAO.