Dietary Modulation of Gut Barrier Function in Streptozotocin-Induced Diabetic Mice: A Comparison of Ketogenic, Short-Chain Fatty Acid-Supplemented, and Iso-caloric Control Diets — ASN Events
  1. Schedule
  2. Joint Poster Session
  3. Dietary Modulation of Gut Barrier Function in Streptozotocin-Induced Diabetic Mice: A Comparison of Ketogenic, Short-Chain Fatty Acid-Supplemented, and Iso-caloric Control Diets

Dietary Modulation of Gut Barrier Function in Streptozotocin-Induced Diabetic Mice: A Comparison of Ketogenic, Short-Chain Fatty Acid-Supplemented, and Iso-caloric Control Diets (#321)

Yousun An 1 2 , Nicholas Norris 1 2 , Johnson Li 1 2 , Jenny Gunton 1 2 3
  1. Centre for Diabetes, Obesity and Endocrinology, Westmead Institute for Medical Research, Westmead, NSW, Australia
  2. Faculty of Medicine & Health, University of Sydney, Sydney , NSW
  3. Department of Diabetes and Endocrinology, Westmead Hospital , Westmead, NSW

 

Intestinal barrier dysfunction contributes to systemic inflammation and metabolic impairment in diabetes. Although ketogenic diets (KD) and short-chain fatty acids (SCFAs) have been shown to improve metabolic health, their comparative effects on gut barrier integrity and the gut–immune axis remain poorly understood. We investigated the effects of isocaloric dietary interventions on gut permeability and metabolic outcomes in streptozotocin (STZ)-induced diabetic mice.

Female C57BL/6J mice were fed an isocaloric control diet, a ketogenic diet, or an SCFA-supplemented diet (2% sodium butyrate and 2% sodium acetate) for five weeks before STZ. Testing included body weight, body composition, blood glucose and ketone measurements, glucose tolerance testing (GTT), and in vivo glucose-stimulated insulin secretion (GSIS) tests. Intestinal permeability was assessed using a FITC-dextran assay. Ileal and colonic tissues were analysed by Alcian Blue/PAS staining to assess mucus barrier integrity. GLP-1 immunohistochemistry evaluated the abundance of enteroendocrine L-cells. Together, these analyses were designed to determine whether dietary interventions preserve gut mucosal integrity and enteroendocrine function, thereby potentially influencing intestinal immune homeostasis and diabetes progression.

Preliminary findings demonstrate distinct metabolic adaptations across dietary groups. KD-fed mice developed sustained nutritional ketosis, whereas SCFA supplementation produced a different metabolic profile despite equivalent caloric intake. Early analyses indicate diet-dependent differences in intestinal barrier integrity following STZ treatment. Histological, inflammatory, and microbiome analyses are ongoing. STZ treatment significantly increased FITC-dextran gut leakiness by >5-fold.

These findings support the concept that dietary interventions influence diabetes not only through metabolic regulation but also through modulation of the gut–immune axis. Preservation of intestinal barrier integrity may attenuate intestinal inflammation and reduce systemic immune activation.