Xia Yang, Sumei Wei, Shiqi Su, Ying Su, Liancheng Lan, Xiuqi Chen, Ting Huang, Qingwen Shan
These findings demonstrate that ZnG exhibits therapeutic potential for AAC through modulation of gut microbiota, enhancement of gut barrier, and regulation of immune responses.
OBJECTIVE: This study aimed to investigate the protective effects of zinc gluconate (ZnG) against antibiotics and peptidoglycan (PGN) induced intestinal injury by targeting gut barrier integrity, macrophage, and gut microbiota homeostasis.
METHODS: Twenty four C57BL/J mice were randomly divided into four groups: normal group (NC), antibiotic cocktail group (ABX), model group (ABX+PGN), and ZnG treatment group (ZnG+ABX/PGN). An antibiotic associated dysbiosis model was established via oral gavage of an antibiotic cocktail, followed by intraperitoneal injection of PGN (10 mg/kg) to simulate Gram positive (G+) bacteria associated challenge in antibiotic associated colitis (AAC) after microbiota disruption. Subsequently, ZnG was administered for therapeutic intervention. Parameters assessed included general condition of mice, intestinal permeability, barrier integrity, macrophage polarization, and gut microbiota composition.
RESULTS: The results indicated that ZnG significantly increased the body weight of the mice treated with ABX and PGN. It also markedly alleviated pathological and ultrastructural damage in the colon. ZnG improved intestinal permeability by reducing serum diamine oxidase (DAO) levels and restored intestinal integrity by upregulating tight junction proteins (TJs), including zonula occludens-1 (ZO-1), Occludin, and mucin 2 (MUC2). In addition, ZnG modulated the macrophage immunity by regulating the expression of polarization associated proteins (iNOS/ARG-1) and inhibited activation of the TLR2-NF-κB signaling pathway. Microbiota analysis revealed that ZnG increased gut microbial diversity while modulating the microbial community structure and its predicted functional potential in mice.
CONCLUSIONS: These findings demonstrate that ZnG exhibits therapeutic potential for AAC through modulation of gut microbiota, enhancement of gut barrier, and regulation of immune responses.