Dietary xylo-oligosaccharides alleviates LPS-induced intestinal injury via endoplasmic reticulum-mitochondrial system pathway in piglets.

ABSTRACT

The beneficial effects of xylo-oligosaccharides (XOS) on the intestine have been widely reported, including anti-inflammation, antioxidant, maintenance of intestinal epithelial barrier, and treatment of intestinal injury. However, the specific mechanism of XOS in mitigating intestinal injury in weaned piglets remains unclear. Therefore, this study aimed to explore the specific mechanism of XOS in mitigating intestinal injury. The study is a complete randomized design with 24 weaned piglets in a 2 × 2 factorial arrangement that includes diet treatments (basal diet vs. 0.02% XOS) and immunological challenge [saline vs. lipopolysaccharide (LPS)]. All piglets were fed a basal diet or a XOS diet for 21 d. On day 22, all piglets received an injection of LPS or saline. In this study, dietary XOS increased jejunal villus height, reduced crypt depth and oxidative stress, and enhanced the gene and protein expression of Claudin-1, Occludin, and zonula occludens 1 (P < 0.05). The piglets fed the XOS diet had lower serum Diamine oxidase activity and d-lactic acid content (P < 0.05). In addition, dietary XOS regulates endoplasmic reticulum (ER)-mitochondria system function and the expression of key molecules, including mitochondrial dynamics dysfunction [mitofusin (Mfn)-1, optic atrophy 1, fission 1, and dynamin-related protein 1], ER stress [activating transcription factor 4 (ATF4), ATF6, C/EBP-homologous protein, eukaryotic initiation factor 2α, glucose-regulated protein (GRP) 78, GRP94, and protein kinase R-like ER kinase] and the mitochondria-associated ER membranes (MAM) disorders (Mfn2, GRP75, and voltage-dependent anion channel 1) (P < 0.05). Therefore, the findings to indicate that dietary XOS is effective against LPS-induced jejunal injury may be attributed to its ability to alleviate mitochondrial dynamics dysfunction, ER stress, and MAM disorders.

Intestinal injury can have a range of negative impacts on weaned piglets. Xylo-oligosaccharides are known for their beneficial effects on the gut, including anti-inflammatory and antioxidant properties, and also help maintain the intestinal epithelial barrier and reduce intestinal injury. However, the exact mechanism by which xylo-oligosaccharides reduce intestinal injury in piglets remains unclear. The endoplasmic reticulum­mitochondrial system, endoplasmic reticulum and mitochondria, along with the mitochondria-associated endoplasmic reticulum membranes that connect them, plays a crucial role in mediating intestinal injury in piglets. Therefore, this study aimed to investigate whether xylo-oligosaccharides affect intestinal injury in piglets through the endoplasmic reticulum, mitochondria, and the mitochondria-associated endoplasmic reticulum membranes. The results of this study indicate that xylo-oligosaccharides mitigate intestinal injury in piglets by alleviating endoplasmic reticulum stress, mitochondrial dynamics dysfunction, and mitochondria-related endoplasmic reticulum membrane disorders, providing a theoretical basis for the treatment of intestinal injury with xylo-oligosaccharides.