(PTFS12-07-23) Alkaline Mineral Complex (AMC) Drives Intestinal Epithelial Regeneration To Prevent Diarrhea by Brain-Microbe-Gut Axis

Objectives: Diarrhea is the fourth-highest mortality rate of all diseases that causes a large number of infant deaths each year. The maternally separated (MS) piglet (Newly weaned piglet) is an excellent model to investigate the treatment of diarrhea in infant. Drinking alkaline mineral water exerts a potential therapeutic efficacy in gastrointestinal disorders, especially diarrhea, but the supportive evidence from system studies and the mechanism involved remain unreported. The aim of this study was to determine whether drinking alkaline mineral water confers diarrhea resistance in MS piglets under weaning stress, and what are the underlying mechanisms involved.

Methods: MS piglets were used to create stress-induced intestinal disorder-diarrhea model. An alkaline mineral complex (AMC) water was employed, and its effect on hypothalamus-pituitary-adrenocortical (HPA) axis, gut microbe, gut morphology, intestinal epithelial cell (IEC) proliferation and differentiation were studied using a range of experimental methods.

Results: AMC water reduced diarrhea rate in MS piglets by inhibiting HPA axis, ameliorating gut microbiota structure and stimulating IEC proliferation and differentiation. Apparently, the brain-microbe-gut axis is linked with AMC water conferring diarrhea resistance in piglets. Mechanistically, AMC water decreased stress hormones (COR and Hpt) secretion by suppressing HPA axis, which then increased the abundance of beneficial gut microbe; accordingly, maintained the proliferation of IEC and promoted the differentiation of intestinal stem cells (ISC) into goblet cell and Paneth cell by activating the Wnt/β-catenin signaling pathway. In the absence of gut microbiota (in vitro), AMC activated the LPS-induced Wnt/β-catenin pathway inhibition in IPEC-J2 cells and significantly increased the number of Lgr5+ cells, whereas did not affect the differentiation of IPEC-J2.

Conclusions: Drinking alkaline mineral water confers diarrhea resistance in MS piglets by maintaining intestinal epithelial regeneration via the brain-microbe-gut axis; thus, this study provides a potential prevention strategy for young mammals at risk of diarrhea.

Funding Sources: This study has received assistance from National Natural Science Foundation of China (No. 32172932).
*Corresponding author: Prof. Jin-Long Li. E-mail address: Jinlongli@neau.edu.cn