# A Combined Probiotic-Morus alba Strategy Enhances Glucose Homeostasis in an In Vitro Gut-Pancreas-Liver Axis Model: A Preliminary Mechanistic Screening Study

## TL;DR

A combination of a probiotic and mulberry leaf extract improves glucose control in a lab model of the gut-pancreas-liver system, suggesting potential for diabetes treatment.

## Contribution

This study demonstrates a novel synergistic effect of a probiotic and plant extract on metabolic pathways relevant to T2DM in an in vitro multi-organ model.

## Key findings

- The combination treatment improved intestinal barrier integrity and increased transepithelial electrical resistance (TEER).
- The treatment reduced pancreatic β-cell dysfunction and increased insulin secretion by 1.7-fold compared to mulberry extract alone.
- The combination modulated key glucose metabolism pathways in liver cells, including IRS1, AKT, AMPK, and PGC-1α.

## Abstract

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder linked to gut microbiota dysbiosis and impaired inter-organ metabolic signalling. This study investigated the combined effects of the probiotic Lactiplantibacillus plantarum TJA7 and Mulberry Leaf extract (Morus alba) on cellular processes relevant to T2DM-related metabolic dysfunction. An advanced in vitro gut–pancreas–liver axis model, using Caco-2, EndoC-βH5, and HepG2 cells, was employed under hyperglycemic and oxidative stress conditions. The combined treatment consistently outperformed the individual components by improving intestinal barrier integrity, as indicated by increased transepithelial electrical resistance (TEER), and by enhancing butyrate translocation across the intestinal layer. Metabolites derived from the combination attenuated pancreatic β-cell dysfunction, reducing reactive oxygen species (ROS) levels and increased insulin secretion (1.7-fold compared with Mulberry Leaf extract alone). At the hepatic level, co-administration modulated key glucose metabolism pathways, including Insulin Receptor Substrate 1 (IRS1), Protein Kinase B (AKT), AMP-Activated Protein Kinase (AMPK), and Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 Alpha (PGC-1α), suggesting improved cellular glucose handling. Collectively, these findings support a positive dose-specific interaction under the tested conditions and provide a biologically plausible, hypothesis-generating framework for probiotic–phytochemical cooperation along the gut–pancreas–liver axis. Further in vivo and clinical studies are required to establish causality and translational relevance.