Porcine and Chicken Intestinal Epithelial Cell Models for Screening Phytogenic Feed Additives—Chances and Limitations in Use as Alternatives to Feeding Trials

Abstract

Numerous bioactive plant additives have shown various positive effects in pigs and chickens. The demand for feed additives of natural origin has increased rapidly in recent years to support the health of farm animals and thus minimize the need for antibiotics and other drugs. Although only in vivo experiments can fully represent their effect on the organism, the establishment of reliable in vitro methods is becoming increasingly important in the goal of reducing the use of animals in experiments. The use of cell models requires strict control of the experimental conditions so that reliability and reproducibility can be achieved. In particular, the intestinal porcine epithelial cell line IPEC-J2 represents a promising model for the development of new additives. It offers the possibility to investigate antioxidative, antimicrobial, anti- or pro-proliferative and antiviral effects. However, the use of IPEC-J2 is limited due to its purely epithelial origin and some differences in its morphology and functionality compared to the in vivo situation. With regard to chickens, the development of a reliable intestinal epithelial cell model has attracted the attention of researchers in recent years. Although a promising model was presented lately, further studies are needed to enable the standardized use of a chicken cell line for testing phytogenic feed additives. Finally, co-cultivation of the currently available cell lines with other cell lines and the development of organoids will open up further application possibilities. Special emphasis was given to the IPEC-J2 cell model. Therefore, all publications that investigated plant derived compounds in this cell line were considered. The section on chicken cell lines is based on publications describing the development of chicken intestinal epithelial cell models.

Olive Mill Waste-Water Extract Enriched in Hydroxytyrosol and Tyrosol Modulates Host–Pathogen Interaction in IPEC-J2 Cells

“…This cell line has been employed in studies focused on pigs' innate immune response to dietary treatments [60], which can be regarded as a reference for in vitro studies of innate immunity in neonatal intra-epithelial cells after dietary stimuli [48,60]. These cells showed high morphological and functional similarities to porcine enterocytes in vivo; therefore, they were employed to evaluate the effects of phytogenic feed additives on swine intestinal epithelium [61]. In recent years, various plant-feed additives have demonstrated antioxidant, antimicrobial, and anti-inflammatory actions and other supporting barrier functions in IPEC-J2 cells [62][63][64][65].…”

Beneficial Effects of Phytogenic Feed Additives on Epithelial Barrier Integrity in an In Vitro Co-Culture Model of the Piglet Gut

“…PFAs are subject to various in vivo and in vitro studies across species, shedding light on diverse areas of potential activity [ 5 , 6 , 7 , 11 , 12 , 21 ] such as immunological status and inflammation [ 16 , 21 , 22 , 23 , 24 , 25 ], gastrointestinal health and barrier integrity [ 16 , 22 , 23 , 24 , 25 , 26 , 27 ], protective effects against pathogens and toxins of various kinds [ 23 , 24 , 25 , 27 ], as well as overall animal growth and performance [ 15 , 21 , 24 , 26 , 27 ]. In general, suitable in vitro models are of significant importance and many available in vitro studies assess specific subprocesses of gut functionality and interactions.…”

“…A typical example are the gut barrier integrity models, for which the Caco-2 cell line is often described as “the gold standard”, even for animals, although it is derived from a human colorectal carcinoma [ 28 , 29 ]. However, similar models have also been described using species-specific cell lines, such as IPEC-J2, an intestinal epithelial cell line derived from the jejunum of a neonatal piglet [ 23 , 28 , 30 , 31 , 32 ]. More complex models employ direct or indirect co-culture of different cell types, e.g., epithelial and immune cells, in order to better approximate the multilayers of in vivo gut processes.…”

“…Furthermore, a limited number of in vitro trials related to intestinal processes with multiple, co-cultured porcine cell lines are available. These trials usually focus on the investigation of the negative effects of toxins and pathogens on the intestinal epithelium [ 23 , 37 , 38 , 39 ]. Recently, a co-culture model of the piglet gut has been described, which utilizes both intestinal porcine epithelial cells from the jejunum of a neonate piglet (IPEC-J2) and peripheral blood mononuclear cells (PBMC) isolated from porcine blood [ 40 ].…”

Alternatives to the Use of Antibiotics in Animal Production

“…It is pivotal to search for naturally occurring, available, low cost and effective growth promoters as substitutes to AGPs in livestock diets, particularly in territories in which antibiotics were banned. Hence, researchers in recent times have been working increasingly on natural alternatives that could replace the use of antibiotics in livestock production for food safety, health, and environmental reasons [8]. Antibiotic alternatives are natural, organic ingredients that could be utilized as feed additives, resulting in promoting growth and the animal's health, primarily exerting their influence on the gastrointestinal tract [9].…”