Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway

Shunfen Zhang; Shanlong Tang; Zhengqun Liu; Huiyuan Lv; Xueying Cai; Ruqing Zhong; Liang Chen; Hongfu Zhang

doi:10.1016/j.phrs.2024.107194

Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway

Pharmacol Res. 2024 Apr 23:204:107194. doi: 10.1016/j.phrs.2024.107194. Online ahead of print.

Authors

Shunfen Zhang¹, Shanlong Tang², Zhengqun Liu³, Huiyuan Lv⁴, Xueying Cai⁵, Ruqing Zhong⁶, Liang Chen⁷, Hongfu Zhang²

Affiliations

¹ State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
² State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
³ State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; Tianjin Key Laboratory of Animal Molecular Breeding and Biotechnology, Tianjin Engineering Research Center of Animal Healthy Farming, Institute of Animal Science and Veterinary, Tianjin Academy of Agricultural Sciences, Tianjin 300381, China.
⁴ College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; Beijing Centre Biology Co., Ltd., Daxing District, Beijing 102218, China.
⁵ Department of Critical Care, Hangzhou First People's Hospital, Hangzhou 310003, China.
⁶ State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address: zhongruqing@caas.cn.
⁷ State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address: chenliang01@caas.cn.

PMID: 38663526
DOI: 10.1016/j.phrs.2024.107194

Abstract

Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p < 0.05) and deterioration of jejunum intestinal morphology, alongside an increase in antibiotic-resistant bacteria such as Staphylococcus, Dolosicoccus, Escherichia-Shigella, and Raoultella. In contrast, baicalin treatment resulted in body weights, intestinal morphology, and microbial profiles that closely resembled those of the control group (p > 0.05), with a significant increase in norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group colonization compared with lincomycin group (p < 0.05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norank_Muribaculaceae and Akkermansia (p < 0.05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.

Keywords: Baicalin; Calcium signaling pathway; Energy metabolism; Intestinal damage; MAPK signaling pathway.