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.

چکیده اصلی

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 Akkermansia muciniphila and Xylanibacter rodentium. No significant global shift in fecal virome composition was observed, although selected viral taxa showed nominal group-associated differences that did not remain significant after FDR correction. Exploratory network analysis suggested group-specific bacteriome-virome association patterns after FMT. 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.

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