Kudzu root-derived carbon dots modulate gut microbiota and metabolites for pan-organ targeted macrophage polarization in synergistic diabetes therapy.
- 2026-06
- Biomaterials 329
- Jianing Yi
- Yuanyu Tang
- Yilin Chen
- Liang Chen
- Dongxue Geng
- Luyao Liu
- Jie Yu
- Lianhong Zou
- Jie Zeng
- Minhuan Lan
- Wenjie Gao
- Ming Gao
- PubMed: 41494302
- DOI: 10.1016/j.biomaterials.2025.123967
Study Design
- Population
- high-fat diet/streptozotocin-induced diabetic mice
- Methods
- Treatment with kudzu root-derived carbon dots (KRCDs), multi-omics analyses, fecal microbiota transplantation
- Funding
- Unclear
- Animal Study
Type 2 diabetes is a systemic disorder characterized by metabolic dysfunction and chronic inflammation, yet strategies that address both aspects remain limited. Here, we present kudzu root-derived carbon dots (KRCDs) as a natural nanomaterial that reprograms the gut microbiota-metabolite-immune axis to restore systemic homeostasis. KRCDs exhibit nanoscale crystallinity, abundant O/N functional groups, and strong antioxidant activity. In high-fat diet/streptozotocin-induced diabetic mice, KRCDs significantly lowered fasting glucose, improved glucose tolerance and insulin sensitivity, corrected lipid profiles, and reduced hepatic steatosis without detectable toxicity. Multi-omics analyses revealed increased microbial diversity, enrichment of beneficial genera such as Anaerostipes, and remodeling of fecal metabolites with a marked rise in indole-3-carboxaldehyde (I3A). This metabolite correlated with enhanced M2-like macrophage polarization across adipose tissue, intestine, kidney, liver, and pancreas, as confirmed by flow cytometry and immunofluorescence. Fecal microbiota transplantation from KRCDs-treated donors reproduced both the metabolic improvements and the organ-wide M2 polarization, confirming a microbiota-dependent mechanism. By establishing a gut microbiota-metabolite-macrophage polarization pathway, KRCDs act as safe, plant-based nanoplatforms that simultaneously correct metabolic and immune imbalance, offering a promising strategy for multi-target intervention in diabetes.