Understanding the impact of protein fermentation end-products on pig intestinal metabolic health to optimize its barrier function (ProBarrier)


Pig health relies critically on well-functioning intestinal epithelium. Epithelial dysfunction causes disruption of the gut barrier resulting in inflammation, diarrhea, mal-absorption of nutrients, and, consequently, reduced growth. After weaning, gut barrier function is often compromised due to prolonged periods of low feed intake. In addition, delayed adaptation to the digestion of vegetable proteins leads to proteins escaping digestion in the proximal small intestine and an subsequent fermentation these can be fermented in the distal small intestine or colon. The end-products of fermentation contribute to the impaired barrier function and thus to the occurrence of post-weaning diarrhea. Intestinal epithelial cells require a vast amount of energetic substrates to power cellular processes that preserve its barrier function. Mitochondria not only generate most of the energy from these energetic substrates, they also form a platform that controls metabolic and immunological and metabolic function of the cell. We postulate that optimal functioning of mitochondria is crucial for maintaining pig gut barrier function. In the proposed research, we analyze the effects of protein fermentation end-products on intestinal epithelial mitochondrial metabolism and signaling in pigs using innovative metabolic and transcriptomic approaches. Furthermore, we will perform high-throughput functional screening of fermentation products on cellular metabolic health and validate whether nutritional compounds that activate mitochondria can protect barrier function from identified adverse protein fermentation products. Finally, we will analyze whether these mito-active compounds, when supplemented in milk before weaning, can support intestinal pig barrier function and protect weaned pigs from post-weaning diarrhea.


Project number


Main applicant

Prof. dr. ir. J. Keijer

Affiliated with

Wageningen University & Research, Dierwetenschappen, Fysiologie van Mens & Dier (HAP)

Team members

Ir. A.F. Bekebrede, Dr. V.C.J. de Boer, J.J.M. Swarts


15/10/2017 to 01/10/2020