The gastrointestinal tract forms a robust line of defense against invading pathogens through the production of endogenous antimicrobial peptides (AMPs), which are crucial molecules of the innate defense system. Tryptophan could modulate intestinal immunity through promoting the expression of AMPs. However, the precise mechanism needs to be further clarified. In this study, we show that treatment with tryptophan for 24 h triggers (p < 0.05) the expression of porcine β-defensin (pBD) 1 (62.67 ± 3.10 pg/mL) and pBD2 (74.41 ± 1.33 pg/mL) in the porcine intestinal epithelial cells (IPEC-J2) though calcium-sensing receptor (CaSR)-tryptophan metabolic pathways. Meanwhile, tryptophan alleviates (p < 0.05) intestinal inflammation induced by lipopolysaccharide (LPS) through induction of the defensins and activation of the CaSR-AMP-activated protein kinase (AMPK) pathways in vitro and in vivo. Moreover, the activation of CaSR induces the expression of defensins and decreases the levels of IL-1β (75.26 ± 2.74 pg/mL) and TNF-α (449.8 ± 23.31 pg/mL) induced by LPS (p < 0.05). Importantly, tryptophan maintains kynurenine homeostasis through the activation of CaSR during the inflammatory response. To that end, the work identifies a regulatory circuit between CaSR signaling and tryptophan metabolic pathways involved in the tryptophan-trigged AMP expression, which contributes to improving intestinal immune defense.

Sodium butyrate alleviates LPS-induced intestinal inflammation in rats by regulating intestinal injury, inflammatory cytokine levels, and intestinal flora.

Host defense peptides (HDPs) are primary components of the innate immune system with diverse biological functions, such as antibacterial ability and immunomodulatory function. HDPs are produced and released by immune and epithelial cells against microbial invasion, which are widely distributed in humans, animals, plants, and microbes. Notably, there are great differences in endogenous HDP distribution and expression in humans and animals. Moreover, HDP expression could be regulated by exogenous substances, such as nutrients, and different physiological statuses in health and disease. In this review, we systematically assessed the regulation of expression and mechanism of endogenous HDPs from nutrition and disease perspectives, providing a basis to identify the specificity and regularity of HDP expression. Furthermore, the regulation mechanism of HDP expression was summarized systematically, and the differences in the regulation between nutrients and diseases were explored. From this review, we provide novel ideas targeted the immune regulation of HDPs for protecting host health in nutrition and practical and effective new ideas using the immune regulation theory for further research on protecting host health from pathogenic infection and excessive immunity diseases under the global challenge of the antibiotic-abuse-induced series of problems, including food security and microbial resistance.

Defensins represent an integral part of the innate immune system to ward off potential pathogens. The study used a rat model to investigate mechanisms by which sodium butyrate (NaB) regulates β-defensin to inhibit lipopolysaccharide (LPS)-induced nephrotoxicity. We found that NaB alleviated LPS-induced renal structural damage, as judged by reduced renal lesions and improved glomerular vascular structure. In addition, elevated levels of indicators of kidney damage creatinine and blood urine nitrogen, inflammatory mediators TNFα, and IL-6 dropped after NaB administration. Rat β-defensin 2 (rBD2), as estimated by mRNA level, was significantly higher in LPS-treated kidneys, whereas the changes of rBD2 reduced in NaB-treated kidneys. In addition, NaB alleviated LPS-induced increase in TLRs mRNA expression. Mechanistically, the present study indicates that NaB has nephroprotective activity resulting from modulation of TLR2/4 to regulate rBD2 expression hence curbing inflammation. Practical applicationsIn practice, adding NaB to diet can improve animal performance. Our results suggest that dietary supplementation of NaB increases animal feed intake and improves the body's defense ability to relieve inflammation caused by bacteria. Especially in the age of resistance prohibition, sodium butyrate can partially replace antibiotics to induce the expression of body defensin. It may become a health care product to enhance the body's immunity.