Trimethylamine N-oxide as a key microbial mediator in the progression of diabetic kidney disease

Table 2 Global diabetes trends that intensify trimethylamine N-oxide -associated fibrotic pathways[2,11-13]

Epidemiologic trend	Underlying biological mechanism	Implication for the TMAO pathway
Increasing consumption of processed foods	Higher dietary intake of choline and carnitine	Greater availability of substrates for microbial trimethylamine formation
Rapid urbanisation	Westernisation of gut microbial composition	Expansion of microbial taxa capable of producing TMA
High proportion of undiagnosed diabetes	Delayed identification of renal injury and prolonged metabolic stress	Increased susceptibility of the kidney to TMAO-mediated fibrotic responses
Rising diabetes prevalence in low- and middle-income regions	Nutritional transition with reduced fibre intake and altered microbial ecology	Amplification of dysbiosis favouring TMA-generating microbiota
Increasing premature mortality in diabetes	Heightened oxidative and inflammatory burden	Lowered threshold for TMAO-driven ROS generation and Smad activation

TMA: Trimethylamine; TMAO: Trimethylamine-N-oxide; ROS: Reactive oxygen species.