Simple SummaryWeaning is a critical period in sow production and induces oxidative damage, which is closely associated with diarrhea, intestinal metabolic disorders, and infections. Probiotics as substitutes for antibiotics play a beneficial role in decreasing diarrhea and improving the growth of weaning piglets. The intraperitoneal injection of lipopolysaccharides (LPS) has been used for inducing oxidative damage and intestinal injury in piglets. In the present study, we investigated the effects of dietaryBacillus licheniformis(BL) on production performance, serum antioxidant capacity, ileal morphology, intestinal short-chain fatty acids (SCFAs), and colonic microflora in piglets challenged with LPS. The results showed that BL supplementation improved growth performance, increased serum catalase activity, decreased malondialdehyde concentration, and increased colonic major SCFAs. Moreover, metagenome analysis showed thatPrevotellaspecies were the predominant bacteria in BL- and CBL-treated piglets. In summary, a basal diet supplemented with 1010CFU BL improved production performance, serum antioxidative capacity, and ileal morphology, and modulated the colonic microflora. This experiment offers theoretical support for dietary probiotic utilization in piglets to decrease weaning stress in the sow industry.AbstractThe aim of the present study was to investigate the effects ofBacillus licheniformis(BL) on the growth performance, antioxidant capacity, ileal morphology, intestinal fecal short-chain fatty acids, and microflora of weaned piglets challenged with lipopolysaccharide (LPS). Piglets were assigned into three groups: basal diet (Con), a basal diet with added 109CFUB. licheniformis/kg (BLl), and a basal diet with added 1010CFUB. licheniformis/kg (BLh). On day 28, BLh piglets were intraperitoneally injected with LPS (CBL) and sterilized saline water (BL), Con piglets were injected with LPS (LPS) and sterilized saline water (Con), with the injections being administered for three consecutive days. The average daily gain significantly increased from day 1 to day 28 and the feed: gain ratio decreased with BL supplementation compared with the Con group. Supplementation with BLl and BLh reduced the diarrhea rate in piglets. Serum catalase activity increased and malondialdehyde concentration decreased in the CBL treatment group compared with the LPS treatment group. Both BL and CBL treatments increased the ileal villus length/crypt depth ratio compared with Con and LPS treatments. BL administration significantly increased colonic propionic and isobutyric acid concentrations compared with Con treatment. Both BL and CBL piglets had significantly increased fecal acetic, propionic, and butyric acid levels compared with LPS piglets. Analysis of the colonic microbial metagenome showed thatPrevotellaspecies were the predominant bacteria in piglets treated with BL and CBL. The CBL-treated piglets had higher scores for lysine biosynthesis, arginine biosynthesis, sulfur relay system, and histidine metabolism. BL-treated piglets had higher scores for glycosaminoglycan biosynthesis-keratan sulfate, oxidative phosphorylation, and pyruvate and carbon metabolism.