Butyrate Mitigates Lipopolysaccharide-Induced Intestinal Morphological Changes in Weanling Piglets by Regulating the Microbiota and Energy Metabolism, and Alleviating Inflammation and Apoptosis

Butyrate provides energy for colonocytes and is a functional metabolite that mitigates weanling piglet stress. However, its effects and mechanisms remain largely unknown. We established a lipopolysaccharide (LPS)-induced inflammatory stress piglet model to examine how butyrate mechanisms impacted piglet intestinal histology, microbiota, and inflammation. We randomly assigned 18 crossbred male piglets to three treatment groups: CON, LPS, and BT-LPS. Coated butyrate was supplemented in the BT-LPS feed for 21 days. On days 19 and 21, piglets in LPS and BT-LPS groups were challenged with LPS at 100 μg/kg body weight. Dietary butyrate improved LPS-injured intestinal histology by significantly increasing jejunal and ileal villus height, villus height to crypt depth ratios, and decreasing histological scores. LPS challenge activated hypoxia-inducible factor 1α and nuclear factor-κB, and enhanced interleukins (IL-1β, IL-6, IL-12), tumor necrosis factor-α, and also downstream inducible nitric oxide synthase and cyclooxygenase 2, but decreased anti-inflammatory cytokines (IL-10, IL-13). Most molecule levels were significantly reversed by butyrate administration. When compared with the CON or LPS groups, the BT-LPS group had a higher relative abundance of jejunal Firmicutes, Bacteroidetes, Clostridiaceae, Lactobacillus, and Prevotella but a lower abundance of Proteobacteria, Enterobacteriaceae, and Escherichia–Shigella. Phylogenetic investigation of communities by reconstruction of unobserved states and correlation analyses suggested these bacteria contributed to butyrate-alleviating jejunal inflammation and infectious diseases. Butyrate-based diets significantly reduced apoptosis via mitochondrial pathways by downregulating apoptotic caspase 3 mRNA levels. Diets also altered enterocyte metabolism in the jejunum by upregulating peroxisome-proliferator-activated receptor α expression but downregulating carnitine palmitoyltransferase 1 level when compared with CON or LPS groups. Butyrate supplementation improved immunity homeostasis, generated beneficial shifts in microbial communities, improved enterocyte energy metabolism, and prevented apoptosis to protect intestinal histology from LPS-induced injury.