Zn glycine mitigates the LPS-induced hepatic injury and inflammation through NrF2/NFκB signaling in geese.

Abstract

Gram-negative bacteria like Escherichia coli have an outer membrane that contains lipopolysaccharide (LPS), which is a powerful inducer of systemic inflammation. It is often associated with gut dysbiosis, intestinal barrier dysfunction, and liver damage. Despite increasing recognition of the gut-liver axis as a critical mediator in systemic inflammation and hepatic pathology, the efficacy of nutritional strategies targeting this pathway remains inadequately defined. This study evaluated the protective effects of zinc glycine (Zn_Gly), a highly bioavailable organic zinc chelate, against LPS-induced gut barrier disruption and liver damage in meat geese. Zn_Gly supplementation @ 80mg/kg of diet significantly attenuated LPS-induced impairments in growth performance, gut morphology, intestinal permeability and liver damage. Zn_Gly reduced considerably (p < 0.01) the levels of LPS in the both liver and ceca, and significantly increased (p<0.01) the expression of tight junction proteins (ZO-1, CLDN-1), thereby mitigating LPS translocation and systemic inflammation (IL-1&#x3b2;, IL-18 and TNF-&#x3b1;) by increasing IL-10 production. Notably, Zn_Gly reversed LPS-mediated oxidative stress by enhancing hepatic antioxidant enzyme activities (SOD, CAT, GSH-Px, T-AOC; p<0.01) and reducing oxidative markers (ROS, MDA, TBARS). Crucially, Zn_Gly mitigated the adverse effects of LPS on liver health by improving ALT, AST, IgG and IgA significantly (p<0.01) leading to reduced Ishaq pathology score and disease related histological parameters. Zn_Gly also improved the hepatic liver metabolism through increasing &#x3b2;-oxidation. Concurrently, Zn_Gly promoted antioxidant defense mechanism NrF2 through upregulation of markers (H0-1, NQO-1 & GCLM). In terms of mechanism, these effects were brought about by blocking the NF-&#x3ba;B signaling pathway, which is essential for the inflammatory liver damage caused by LPS. These findings elucidate Zn_Gly as a promising nutritional modulator of the gut-liver axis, attenuating systemic inflammation and conferring protection against inflammation-induced liver damage. This underscores its therapeutic potential for improving animal health and guiding translational strategies in metabolic disorders associated with gut and hepatic dysfunction.