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

Table 3 Evaluation of interventions that are experimental vs clinically applicable[203-205,207-210,212]

No.	Category	Intervention	Clinical status	Key rationale (with citations)	Ref.
1	Clinically applicable	Dietary modification (high-fibre, Mediterranean-style diet)	Clinically recommended	Improves glycaemic control, reduces inflammation, increases SCFA-producing taxa; supported by clinical and mechanistic evidence summarized in reviews	Salas-Salvadó et al[205]
2		Lifestyle interventions (exercise, weight loss)	Clinically established	Proven metabolic benefits with beneficial shifts in microbiome composition; supported by human observational and mechanistic summaries	Amerkamp et al[212]
3		Commercial probiotics (adjunctive, strain-specific)	Limited clinical applicability	Human studies show modest, strain-dependent metabolic improvements; discussed in multiple review articles as adjuncts rather than stand-alone therapies	Kocsis et al[204]
4	Experimental/research-stage	Fecal microbiota transplantation	Investigational	Pilot RCTs show transient improvements but inconsistent outcomes; safety and standardization concerns limit clinical use	Wu et al[203]
5		TLR antagonists (TLR4/TLR9 inhibitors)	Preclinical/early translational	Reduce metabolic inflammation in models; minimal human data and ongoing safety concerns	Yehualashet[208]
6		TMA/TMAO pathway inhibitors	Preclinical/early translational	Lower TMAO and inflammatory signaling in animal models; no large human trials	Jaworska et al[209]
7		Next-generation or engineered probiotics	Early clinical/experimental	Promising metabolic effects in early translational studies; require larger clinical trials	Kocsis et al[204]
8		SCFA/butyrate supplementation	Experimental	Mechanistically beneficial but limited robust human evidence; diet-induced endogenous SCFA remains preferred	Arora and Tremaroli[210]
9		Antibiotic-based microbiota depletion	Experimental	Mechanistically informative but clinically unsuitable due to resistance, dysbiosis risk and lack of durable benefits	Mikkelsen et al[207]

TLR: Toll-like receptor; TMAO: Trimethylamine-N-oxide; TMA: Trimethylamine; SCFA: Short-chain fatty acid; RCT: Randomized controlled trial.