Data Availability StatementThe data used to aid the findings of the research are available through the corresponding writer upon request. the only protein source in this study. Fourteen piglets (7.98 0.14?kg, weaned at 28?d) were randomly allotted to two dietary treatments: a control group (Cont, containing 17% casein) and a high protein group (HP, containing 30% casein). The experiment lasted for two weeks and all animals were free to eat and drink water ad libitum. The diarrhea score (1 = normal; 3 = watery?diarrhea) and growth performance were recorded daily. The results showed that this piglets in HP group had persistent diarrhea during the whole study, while no diarrhea was noticed in the control groups. Also, the feed intake and body weights were reduced in the HP Wortmannin cell signaling groups compared with the other group ( 0.05). The diarrhea-related mRNA abundances were analyzed by real-time PCR; the results showed that HP treatment markedly decreased the expression of aquaporin (AQP, 0.05) and the tight junction protein (P 0.05), but increased inflammatory cytokines ( 0.01) than those in control group. In addition, the Adenosine 5-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway ( 0.01) was inhibited in the HP group. Intestinal microbiota was tested by 16S sequencing, and we found that the HP group had a low diversity compared the other group. In conclusion, despite being highly digestible, a high casein diet induced postweaning diarrhea and reduced the growth performance of the postweaning piglets. Meanwhile, AQP, tight junction protein, and Wortmannin cell signaling intestinal immune were compromised. Thus, the mechanism of how a highly digestible protein diet induces diarrhea might be associated with the AMPK signaling pathway and intestinal microbiome. 1. Introduction In many countries, folks are attempting against infections still, allergy, and too little powerful dietary control for the infantile diarrhea [1]. Infantile diarrhea is normally distinguished as severe for diarrhea carrying on exist for approximately 14 days or acting being a chronic disease if the diarrhea will last beyond 14 days [2]. Diarrhea disease induces great mortality and morbidity in kids younger than five years [3]. Speaking Generally, gastrointestinal T illnesses certainly are a main reason behind infantile diarrhea, which induces serious morbidity and mortality among small children. Further, most gastrointestinal illnesses are connected with gut microbiota and their products [4] carefully. The composition from the gastrointestinal microbiota is certainly affected by nutritional nutrition intake, for instance, the three primary nutritional elements, proteins, sugars, and extra fat [5]. Proteins may be the many important element of tissue in human beings and pets, and, unlike sugars, high concentrations of eating proteins intakes you could end up many deleterious metabolites in the gut [6]. Levels of studies that targeted at figure out the consequences of proteins on infantile and model pets have showed the fact that concentration and resources of eating protein are potential factors behind diarrhea in mammals [7]. People from the aquaporins (AQP) family members act as drinking water and ion transporters and full the rapid transport of drinking water through membranes in the digestive tract in Wortmannin cell signaling the human body; water, via sensitive AQPs, is essential in the migration via diarrhea. While as Zonula occluden-1(ZO-1) and occludin can dynamically affect intercellular permeability. We selected these markers to illustrate the characteristics of diarrhea. To better understand nutritional control around the development of an Wortmannin cell signaling individual infantile diarrhea, piglets’ model has been chosen as an experimentally analog to human diets. The chosen animal model has been indicated the effects of high protein levels in daily diets on diarrhea, including reduced growth performance, severely watery feces, and gastrointestinal dysfunction. In this work, we have investigated two postweaning piglets’ diets that reflected protein’s effects on diarrhea. These diets included a control group (Cont, made up of 17% casein) and a high protein group (HP, made up of 30% casein) that led to an excessive intake of protein compared to that shown.