Microbiota-metabolites interaction associated with glycemic improvement following a dietary herbal intervention in...

Type 2 diabetes (T2D) is a global metabolic disorder characterized by chronic hyperglycemia and disruption of the gut microbiome. Nutritional and microbiota-targeted interventions have emerged as promising strategies for glycemic management, yet longitudinal clinical evidence integrating microbial and metabolic mechanisms remains limited. This study investigated microbiota-metabolites alterations during a standardized dietary herbal intervention (QingYun7, QY7) and explored their relationship with glycemic regulation across both animal study and clinical settings.

The metabolic and microbial effects of QY7 were first evaluated in diabetic rats through measurements of blood glucose, and gut microbiota composition. Subsequently, a prospective cohort of 385 patients with T2D received QY7, with longitudinal monitoring of fasting, random, and 2-h postprandial glucose, gut microbiota, and serum metabolites across multiple time points. Fecal microbiota transplantation (FMT) from patients before and after intervention into antibiotic-treated mice was performed to evaluate the causal contribution of the gut microbiome to glycemic improvement. Mediation analyses were conducted to delineate potential pathways linking gut microbes, serum metabolites, and glucose outcomes.

In diabetic rats, QY7 administration significantly reduced blood glucose, and restored gut microbial composition. In the clinical cohort, the intervention was associated with rapid and sustained reductions in fasting, random, and postprandial glucose levels, accompanied by consistent remodeling of the gut microbiome and serum metabolite profile. FMT experiments demonstrated that microbiota derived from post-intervention patients conferred improved glycemic responses in recipient mice, supporting a causal role of gut microbiota in metabolic regulation. Serum metabolomic profiling revealed significant alterations, including enrichment of branched-chain amino acid related pathways. Mediation analyses identified key metabolites, phenyllactic acid, 3-methyl-2-oxobutanoic acid, and anandamide, as mediators linking specific bacterial taxa (Alistipes shahii and Limosilactobacillus mucosae) to fasting and postprandial glucose levels.

This study provides translational evidence that a dietary herbal intervention associated with glycemic improvement in T2D through microbiota-mediated metabolic reprogramming. Gut microbiome alterations induced by the intervention exerted causal effects on blood glucose regulation, with serum metabolites acting as potential key intermediaries. These findings highlight the mechanistic insight in nutrition-based microbiome modulation strategy in T2D.