Weaning piglets usually are burdened with gastrointestinal infections, mainly enterotoxigenic Escherichia coli (ETEC) diarrhea, which is involved in the death of approximately 17% of piglets born in Europe [1]. ETEC is an important cause of many diseases in piglets, including neonatal diarrhea, post-weaning diarrhea, edema, and sepsis [2,3]. ETEC has a minimum 6-month survival life in the environment [4]. E. coli F4 (K88) has a specific type of fimbriae which allows it to colonize the small intestine and release enterotoxins heat-labile toxin (LT), heat-stable toxin type I (STa), and heat-stable toxin type II (STb), which induce the secretion of fluid into the intestinal lumen by epithelial cells and lead to diarrhea [5].

Tryptophan (Trp) is a limiting amino acid for pigs. Trp intake 10 times higher than the minimum requirement can promote growth [6,7]. Trp participates in protein synthesis, promotes growth, regulates the secretion of animal gastric growth hormone to promote feed intake, stimulates insulin release, and promotes glycogen synthesis in liver and muscle cells [8]. Trp is the precursor of a variety of biologically active compounds, including kynurenine (Kyn) and 5-HT. It has been suggested that most of the dietary Trp may be metabolized via the kynurenine pathway and that Trp has reduced in the blood of patients with major depressive disorder, bipolar disorder, and schizophrenia. This reflects the relative importance of its possible involvement in the pathophysiology of mental disorders [9]. It also has an immunomodulatory effect. Supplementing Trp increases interferon-γ (IFN-γ), IgG, and IgM levels in the body [10], increases sow lactation [11], and promotes differentiation and proliferation of lymphocytes and T cells [12], [13], [14].

BD is a type of cationic polypeptide primarily expressed in skin and mucosal epithelial cells [15]. BD has direct bactericidal, fungicidal, and virucidal activities [16]. Accordingly, recombinant pig BD-2 has been successfully used as a feed supplement for weaned piglets to increase growth and lessen postweaning diarrhea [17]. Also, oral administration of synthetic BD reduced the colonization of enterotoxic E. coli F4 in the intestine [18]. Trp directly activated mTOR and bioactives to play important physiological functions [19]. Intestinal epithelial cells expressed BD more frequently when Trp was present [20].

Our previous work found that Trp and its metabolite Kyn facilitated the BD production in the jejunal mucosa of piglets, whereas 5-HT had no discernible impact on the BD expression [21]. Our earlier work also observed that a diet based on corn and soybean meal with 0.35% Trp reduced the rate of diarrhea and improved growth performance, intestinal mucosal development, and microbial ecology in the hindgut as shown by the rising levels of ADG and FCR, as well as the intestine antibacterial peptides (porcine BD-2) were upregulated [7]. The increase of beneficial microorganisms in the small intestine of weaned piglets, the activation of mTOR signaling, and the Trp metabolites were all linked to these advantageous effects of 0.35% Trp. However, it was not clear whether adequate provision of Trp had protective effects on growth and the function of intestinal epithelial barrier in weaned piglets exposed to porcine ETEC. Therefore, in this study we investigated the protective effects of dietary Trp on growth and gut epithelial barrier performance in weaned piglets infected with porcine E. coli F4. To further validate Trp is a functional nutrient that contributes to the maintenance of intestinal homeostasis, and to provide reference data on the dose of Trp added to diets, the function of Trp metabolism, and defense mechanisms in young animals.