Circulating microbiome and its clinical implications in diabetes mellitus: Mechanistic insights and therapeutic perspectives

Table 1 The relationship between key microbial components/metabolites (lipopolysaccharide, short-chain fatty acids, trimethylamine-N-oxide) and their associated clinical outcomes in diabetes[200-202]

No.	Microbial component/metabolite	Source/mechanism	Key biological effects	Clinical outcomes in diabetes	Ref.
1	Lipopolysaccharide	Outer membrane of gram-negative bacteria; translocates into circulation during gut barrier dysfunction	Activates TLR4; drives systemic inflammation, insulin resistance, and β-cell stress	Chronic low-grade inflammation (“metabolic endotoxemia”)	Kim and Sears[200]
	Worsened insulin resistance
	Increased risk of type 2 diabetes
	Endothelial dysfunction and cardiovascular complications
2	Short-chain fatty acids (acetate, propionate, butyrate)	Fermentation of dietary fibre by beneficial gut bacteria	Regulate gut barrier integrity, GLP-1 secretion, energy homeostasis, and immune tolerance	Improved insulin sensitivity	Nogal et al[201]
	Enhanced glycemic control
	Reduced inflammation
	Butyrate deficiency linked to dysbiosis and impaired metabolic regulation
3	TMAO	Produced by gut microbial metabolism of choline/carnitine converted to TMAO in liver	Promotes inflammation, oxidative stress, and vascular dysfunction	Increased risk of type 2 diabetes	Brunt et al[202]
	Higher incidence of atherosclerotic cardiovascular disease
	Elevated diabetic nephropathy progression risk

TMAO: Trimethylamine-N-oxide; TLR: Toll-like receptor; GLP-1: Glucagon-like peptide-1.