Alleviating effects of Lactobacillus rhamnosus on microcystin-LR-induced hepatotoxicity in zebrafish through regulation of intestinal metabolism: Insights into the gut-liver axis and hypothalamic-pituitary-thyroid axis.

Microcystin-LR (MC-LR) is a highly toxic cyanobacterial metabolite whose potent hepatotoxicity is well recognized. Probiotic Lactobacillus rhamnosus (LGG) has been demonstrated to adjust intestinal microecology and alleviate multi-organ toxicity in fish induced by environmental water pollutants. However, its potential in alleviating MC-LR-induced hepatotoxicity remains poorly explored. This study assessed the benefits of LGG on zebrafish liver after MC-LR exposure and explored the key role of intestinal metabolism within it. Histopathology and liver damage marker results showed that LGG dietary supplementation significantly alleviated liver damage in zebrafish exposed to MC-LR (0, 2.2, and 22 μg/L) for 28 days. Liver transcriptomic analysis confirmed that LGG mitigated liver inflammation and oxidative stress, which are closely related to liver damage. Furthermore, gut metabolomic analysis revealed that LGG restored disorders of lipid and organic acid metabolism induced by MC-LR. This restoration contributes to relieving hepatotoxicity through the gut-liver axis. The improvement of intestinal metabolism by LGG also helps maintain the homeostasis of the hypothalamic-pituitary-thyroid axis, affecting the levels of thyroid hormones and their specific receptors to effectively regulate liver health. This study offers scientific validation for utilizing probiotics to address MC-LR-related environmental pollution and protect aquatic organisms.