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We studied the effect of early pathogenic  Escherichia coli  infection on newborn calves’ intestinal barrier and immune function. A total of 64 newborn Holstein male calves (40–43 kg) were divided into two groups: normal (NG) and test (TG), each with 32 heads. At the beginning of the experiment, the TG calves were orally administered pathogenic  E. coli  O1 (2.5 × 10 11  CFU/mL, 100 mL) to establish a calf diarrhea model. In contrast, the NG calves were given the same amount of normal saline. During the 30 d trial period, the feeding and management of the two groups remained constant. Enzyme-linked immunosorbent assay, quantification PCR, and high-throughput 16S rRNA sequencing technology were used to detect indicators related to the intestinal barrier and immune function in the calf serum and tissues. Pathogenic  E. coli  O1 had a significant effect on calf diarrhea in the TG; it increased the bovine diamine oxidase ( P  &amp;lt; 0.05) and endotoxin levels in the serum and decreased ( P  &amp;lt; 0.05) the intestinal trefoil factor ( P  &amp;lt; 0.05),  Occludin, Claudin-1 , and  Zonula Occludens 1 (ZO-1)  levels in the colon tissue, as well as downregulated the mRNA expression of  Occludin, Claudin-1 ,and  ZO-1  in the colon mucosa, leading to increased intestinal permeability and impaired intestinal barrier function. Additionally, pathogenic  E. coli  had a significant impact on the diversity of colonic microbial flora, increasing the relative abundance of Proteobacteria at the phylum level and decreasing the levels of Firmicutes and Bacteroides. At the genus level, the relative abundance of  Escherichia  and  Shigella  in the TG increased significantly ( P  &amp;lt; 0.05), whereas that of Bacteroides,  Butyricicoccus , Rikenellaceae_RC9_gut_group,  Blautia , and  Lactobacillus  was significantly decreased ( P  &amp;lt; 0.05). In addition, the level of IL-6 in the serum of the TG calves was significantly increased ( P  &amp;lt; 0.05), whereas the IL-4 and IL-10 levels were significantly decreased ( P  &amp;lt; 0.05), compared to those in the NG calves. Thus, pathogenic  E. coli  induced diarrhea early in life disrupts intestinal barrier and impairs immune function in calves.

Effect of Early Pathogenic Escherichia coli Infection on the Intestinal Barrier and Immune Function in Newborn Calves