Modulation of gut microbiota, up-regulation of ZO-1, and promotion of metabolism as therapeutic mechanisms of indole-3-carbinol against obesity in mice

Background: Indole-3-carbinol (I3C) is a compound derived from Cruciferous vegetables. We aim to ascertain whether I3C mediates the relations between mouse gut microbiota, intestinal barrier function, and metabolism to treat obesity in mice.

Methods: The experimental analyses focused on the changes in lipid distribution, inflammatory cytokines, glucose tolerance, gut microbiota composition, and serum metabolomics of 60 C57BL/6N mice.

Results: The experimental results demonstrated that I3C reduced body weight, hepatic steatosis, and systemic inflammation and improved insulin resistance in mice on a high-fat diet (HFD). Furthermore, I3C remarkably enhanced the enrichment of probiotics Akkermansia and Ligilactobacillus as well as SCFA-producing bacteria (Eubacterium, Lactococcus, and Coprococcus), while reducing the abundance of Eisenbergiella and Rikenellaceae_RC9_gut_group. Also, I3C notably up-regulated the levels of Claudin4, Occludin, and ZO-1 proteins and modulated the metabolism of argininosuccinic acid and galactose.

Conclusion: The aforementioned findings suggest that I3C exerts a significant anti-obesity effect in mice by regulating abnormal gut microbiome, enhancing intestinal barrier function, and improving metabolic disorders.