Weizmannia coagulans BC2000 Plus Ellagic Acid Inhibits High-Fat-Induced Insulin Resistance by Remodeling the Gut Microbiota and Activating the Hepatic Autophagy Pathway in Mice

(1) Background: Ellagic acid (EA) acts as a product of gut microbiota transformation to prevent insulin resistance, which is limited by high-fat diet (HFD)-induced dysbiosis. The aim of this study was to investigate the synergistic effects and mechanisms of supplementation with the probiotic Weizmannia coagulans (W. coagulans) on the prevention of insulin resistance by EA; (2) Methods: C57BL/6J mice were divided into five groups (n = 10/group): low-fat-diet group, high-fat-diet group, EA intervention group, EA + W. coagulans BC77 group, and EA + W. coagulans BC2000 group; (3) Result: W. coagulans BC2000 showed a synergistic effect on EA’s lowering insulin resistance index and inhibiting high-fat diet-induced endotoxemia. The combined effect of BC2000 and EA activated the autophagy pathway in the mouse liver, a urolithin-like effect. This was associated with altered β-diversity of gut microbiota and increased Eggerthellaceae, a potential EA-converting family. Ellagic acid treatment alone and the combined use of ellagic acid and W. coagulans BC77 failed to activate the hepatic autophagy pathway; (4) Conclusions: W. coagulans BC2000 can assist EA in its role of preventing insulin resistance. This study provides a basis for the development of EA-rich functional food supplemented with W. coagulans BC2000.