Bacteriophage as an Alternative to Antibiotics Promotes Growth Performance by Regulating Intestinal Inflammation, Intestinal Barrier Function and Gut Microbiota in Weaned Piglets

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 four dietary treatments with five pens/treatment and six piglets/pen in a 21-d feeding trial. The control diet was supplemented with 25 mg/kg quinocetone and 11.25 mg/kg aureomycin in the basal diet, while the three treatment diets were supplemented with 200, 400, or 600 mg/kg bacteriophage in the 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 average daily gain and average daily feed intake, and decreased feed/gain ratio and diarrhea incidence of weaned piglets (P < 0.05). Also, piglets fed 400 mg/kg bacteriophage had elevated villi height (VH) in jejunum and ileum, reduced crypt depth (CD) in jejunum and ileum, and elevated VH/CD ratio in duodenum, jejunum and ileum (P < 0.05). Compared to the control group, piglets fed 400 mg/kg bacteriophage had lower interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and higher interleukin-10 (IL-10) concentration in serum, and higher secretory immunoglobulin A (sIgA), intestinal trefoil factor (ITF), and tumor growth factor-alpha (TGF-α) content in the ileal mucosa (P < 0.05). Besides, dietary addition with 400 mg/kg bacteriophage decreased the D-lactate concentration and diamine oxidase (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 changes in the relative abundance of Firmicutes, Bacteroidetes, and Tenericutes (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.