AUTHOR=Zeng Yongdi , Wang Zirui , Zou Tiande , Chen Jun , Li Guanhong , Zheng Liuzhen , Li Shuo , You Jinming TITLE=Bacteriophage as an Alternative to Antibiotics Promotes Growth Performance by Regulating Intestinal Inflammation, Intestinal Barrier Function and Gut Microbiota in Weaned Piglets JOURNAL=Frontiers in Veterinary Science VOLUME=Volume 8 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2021.623899 DOI=10.3389/fvets.2021.623899 ISSN=2297-1769 ABSTRACT=This study aimed to investigate the effects of dietary bacteriophage supplementation on growth performance, intestinal morphology, barrier function, and intestinal microbiota of weaned piglets fed antibiotic-free diet. A total of 120 weaned piglets were allotted to 4 dietary treatments with 5 pens/treatment and 6 piglets/pen in a 21-d feeding trial. The 4 diets were added with antibiotics (25 mg/kg quinocetone and 11.25 mg/kg chlortetracycline), 200, 400, or 600 mg/kg bacteriophage in the antibiotic-free basal diet, respectively. There was no difference for growth performance and all measured indices of serum and intestinal tissues between 200 mg/kg bacteriophage group and the control group with antibiotics (P > 0.05). More importantly, compared with the control diet, dietary 400 mg/kg bacteriophage inclusion increased ADG and ADFI, and decreased F/G and diarrhea incidence of weaned piglets (P < 0.05). Also, piglets fed 400 mg/kg bacteriophage had elevated VH in jejunum and ileum, reduced CD in jejunum and ileum, and elevated VH/CD in duodenum, jejunum and ileum (P < 0.05). Piglets fed 400 mg/kg bacteriophage had lower IL-1β and TNF-α, and higher IL-10 concentration in serum, and higher sIgA, ITF, and TGF-α content in the ileal mucosa (P < 0.05). Besides, dietary addition with 400 mg/kg bacteriophage decreased the D-lactate concentration and DAO activity in serum, and increased the relative mRNA expression of ZO-1, Claudin-1, Occludin, TLR2, TLR4 and TLR9, as well as the relative protein expression of Occludin in the jejunum (P < 0.05). However, the growth performance and all analyzed parameters in serum and intestinal tissues were not further improved when piglets fed 600 vs. 400 mg/kg bacteriophage (P > 0.05). MiSeq sequencing analysis showed that bacteriophage regulated the microbial composition in caecum digesta, as indicated by higher observed_species, Chao1, and ACE richness indices, as well as the relative abundance of some beneficial bacterial species, such as Firmicutes, Bacteroidetes, Tenericutes, and Ruminococcaceae (P<0.05). Collectively, 400 mg/kg bacteriophage can be used as an antibiotics alternative for promoting the growth of weaned piglets. The underlying mechanism is associated with a positive effect of bacteriophage on intestinal inflammation, intestinal barrier function and gut microbiota in weaned piglets.