Effects of Sargassum plagiophyllum kombucha on insulin sensitivity and inflammation markers in diabetic rats

This study evaluated the physicochemical characteristics, microbial composition, bioactive metabolites, and functional effects of Sargassum plagiophyllum kombucha in diabetic rats. Kombucha was produced through a 16-day SCOBY fermentation, during which pH and sugar content decreased, while 14 metabolites were identified by liquid chromatography-mass spectrometry (LC–MS). The Prediction of Activity Spectra for Substances (PASS) online tool predicted that several identified metabolites, including polydatin and swertiamarin, have potential antihyperglycaemic and anti-inflammatory activities. Five probiotic species were detected, with Weissella cibaria being dominant. Male Wistar rats were divided into normal controls, diabetic controls, and diabetic rats receiving S. plagiophyllum kombucha (1 ml per administration) once, twice, or three times daily following streptozotocin induction. After 4 weeks of intervention, kombucha demonstrated dose-dependent improvements in fasting glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and the expression of glucose transporter type 4 (GLUT4) and Ras-related protein Rab-13 (Rab13), with twice-daily administration having the most favourable metabolic outcomes. Pro-inflammatory cytokines (TNF-α, IL-1β) in CD4 cells were markedly reduced, and IL-4 levels were significantly increased in the twice-daily group. Three-times-daily administration was associated with attenuated metabolic responses compared with twice-daily administration. The observed antihyperglycaemic and anti-inflammatory effects of S. plagiophyllum kombucha are likely to be mediated by the combined contributions of multiple fermentation-derived metabolites and probiotic activity, rather than by a single dominant compound. These findings suggest that moderate kombucha intake (twice daily) provides the most effective metabolic and inflammatory improvements in this experimental model.