Colon-targeting potential and metabolic effects of sodium butyrate-loaded CPC microspheres in type 2 diabetic mice
Year: 2026
Type: article
Abstract: Background Oral sodium butyrate (SB) is rapidly absorbed in the proximal small intestine, limiting its colonic availability and local metabolic effects. We evaluated the in vitro release characteristics of chitosan-protocatechualdehyde/calcium alginate microspheres loaded with SB (CPC/SB), together with metabolic and microbial outcomes in mice with high-fat diet/streptozotocin-induced diabetes. Methods CPC/SB release was measured in separate simulated gastric, intestinal, and colonic fluids. Thirty-five male C57BL/6J mice were assigned to seven groups: normal control and six diabetic groups receiving vehicle, unloaded CPC, free SB, CPC/SB, metformin, or metformin plus CPC/SB for 4 weeks (34 completed). Endpoints included gastrointestinal and fecal butyrate; blood glucose, homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein cholesterol (LDL-C), and interleukin-6 (IL-6); and fecal microbiota assessed by 16S rRNA gene sequencing and PICRUSt2. Results Relative butyrate release was 0.91%, 8.53%, and 94.17% in simulated gastric, intestinal, and colonic fluids, respectively. After CPC/SB administration, colonic butyrate exceeded gastric and small-intestinal levels, and fecal butyrate increased versus the model group (0.0523 ± 0.0121 vs. 0.0180 ± 0.0068 μg/mg; p < 0.0001). Random blood glucose decreased to 18.64 mmol/L at week 4 ( p < 0.0001 vs. baseline and model). CPC/SB also reduced HOMA-IR (3.14 ± 0.43 vs. 4.81 ± 1.30; p = 0.046) and serum IL-6 (85.82 ± 1.90 vs. 93.55 ± 4.10 pg./mL; p = 0.008); LDL-C and α-diversity were unchanged. Exploratory 16S analyses suggested taxonomic and predicted pathway differences, but none survived Benjamini-Hochberg correction. Conclusion At the tested dose, CPC/SB increased fecal butyrate, improved glycemic indices, and reduced serum IL-6 relative to the diabetic model group. SB, carrier, and delivery-related effects could not be separated, and in vivo targeting efficiency was not demonstrated.
Source: Frontiers in Nutrition
Authors: Qinqin Zhang, Gaiqi Yao
Institution: Peking University Third Hospital
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7224116241
