Fecal microbiota transplantation from duodenal light stimulation-conditioned donors is associated with improved glucose tolerance and intestinal incretin-related remodeling in diabetic Goto-Kakizaki rats.

Background: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by impaired glucose homeostasis and β-cell dysfunction. Emerging evidence suggests that the gut microbiota-incretin axis may contribute to metabolic regulation. However, whether microbiota from duodenal light stimulation (DLS)-conditioned donors can influence metabolic phenotypes via fecal microbiota transplantation (FMT) remains unclear. Methods: We evaluated whether FMT from DLS-conditioned donors was associated with metabolic and intestinal changes in diabetic GK (Goto-Kakizaki) rats. Recipients received FMT from week -2 to week 0 and were then followed for 7 weeks after the final FMT dose. Metabolic phenotyping, intestinal histology, short-chain fatty acid (SCFA) profiling, and shotgun metagenomic profiling of bacterial and viral communities were performed. Results: FMT recipients showed within-group improvement in OGTT glucose profiles, without significant changes in fasting glucose levels. Total glucose AUC0-120 was significantly reduced within the FMT group in the within-group (period) comparison; however, the group × period interaction was not significant, indicating no statistically significant longitudinal between-group treatment effect. Early GLP-1 responses showed a modest increasing trend in FMT recipients, whereas total GLP-1 AUC0-120 was not significantly changed. HOMA-β (homeostatic model assessment of β-cell function) increased within the FMT group, and pancreatic insulin-positive area was greater in FMT recipients than in controls at the study endpoint. Intestinal remodeling was evident, including an increased villus:crypt ratio and increased colonic GLP-1-positive cells. FMT was associated with fecal bacteriome differences, including one FDR-significant taxon and several nominally associated taxa, such as Conclusion: FMT from DLS-conditioned donors was associated with improved glucose tolerance, intestinal incretin-related remodeling, increased pancreatic insulin-positive area, and fecal bacteriome differences in diabetic GK rats based on within-group longitudinal changes for the glucose- and β-cell-related outcomes, for which the group × period interactions were not significant, whereas the histological and microbiome differences reflect cross-sectional between-group comparisons at the study endpoint. These findings support a hypothesis-generating link between donor-conditioned FMT, intestinal remodeling, and microbiome-associated metabolic regulation, while further studies are required to define DLS-specific and donor-derived effects.