SAT-577 - Targeting the gut-kidney-bone axis in diabetes with sorghum bicolor.

Background:
Diabetic nephropathy (DN) is a major cause of end-stage renal disease worldwide and is associated with increased mortality among individuals with diabetes. Despite its growing burden, effective therapeutic options remain limited. Emerging evidence suggests that gut dysbiosis contributes to renal injury; however, the underlying mechanisms are not fully understood. This study aimed to investigate the role of gut-derived metabolites in diabetic kidney disease (DKD) and to evaluate the protective potential of methanolic crude extract of Sorghum bicolor (red sorghum; great millet) using in vitro models representing the gut–kidney–bone axis.

Methods:
Metabolomic profiling of stool and urine samples from patients with type 2 diabetes mellitus (T2DM), DN, and healthy controls was performed using GC–MS analysis. Differential metabolites were identified through statistical and ROC curve analyses. Selected candidate metabolites were evaluated for their effects on cytotoxicity, oxidative stress, and apoptosis in HEK-293 (kidney) and MG-63 (osteosarcoma) cell lines. Co-treatment experiments were conducted using the red sorghum seed extract to assess its protective effects.

Results:
Distinct metabolomic signatures were observed across study groups. Five candidate biomarkers— hydroxyphenyllactic acid, hydroxy isovaleric acid, Isocitric acid lactone, stearic acid, and propionic acid —demonstrated significant induction of reactive oxygen species (ROS) in both HEK-293 and MG-63 cell lines, with effects comparable to the positive control (H₂O₂). Notably, co-treatment with red sorghum seed extract significantly attenuated ROS generation and reduced apoptosis in both cell lines.

Conclusion:
Our findings underscore the role of gut-derived microbial metabolites in mediating multi-organ dysfunction, supporting the concept of a gut–kidney–bone axis in diabetes-related complications. Furthermore, Sorghum bicolor seed extract exhibits protective effects against metabolite-induced oxidative stress and apoptosis, highlighting its potential as a novel therapeutic candidate for diabetic nephropathy.

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