An intensive milk replacer feeding program benefits immune response and intestinal microbiota of lambs during weaning

BACKGROUND: Pre-weaning milk replacer (MR) feeding program is a key factor affecting the health and welfare of lambs during their weaning. Weaning stress is well known as an inducement that negatively impacts the immune system of young ruminants, whose physiological and immune state is closely linked to the community of microbiota in their intestines. This study had two objectives: 1) To evaluate the innate immune response to weaning stress at both the physiological and molecular level; 2) To investigate changes to the jejunal chyme and mucosal adhesive microbiota between the control and high plane of MR groups. RESULTS: In this experiment, the plasma concentrations of cortisol, norepinephrine (NE) and tumor necrosis factor-α (TNFα) were higher in the C than the H group (P < 0.05), as was the expression of pro-inflammatory cytokines such as TNFα and CXCL8 (P < 0.05) in plasma. In jejunal tissue, the expression of TLR4 and TNFα were also higher in the C group (P < 0.01); histopathology showed the H group had lower lymphocyte infiltration. In the C group, however, major pathological changes were associated with extensive infiltration of lymphocytes, eosinophils, and neutrophils. Principal component analysis indicated the lamb immune response was influenced by weaning stress and modulated by the MR treatments. 16S-rRNA sequencing was used to evaluate jejunal mucosa and chyme bacterial diversity and composition. The C group’s chyme had a greater alpha index (ACE: P = 0.095; Chao1: P = 0.085) than H group. In jejunal mucosa, the relative abundance of Plesiomonas was 4-fold higher (P = 0.017) in the C than the H group. CONCLUSIONS: This study’s results revealed that weaning stress induced alterations to the lambs’ immune system that lasted beyond the 21 d measured, and that a long-term inflammatory response effect was evidenced by changes in their hematological and expressed pro-inflammatory cytokines. Pre-weaning with a differing MR allowance resulted in complicated biological responses and compositional changes to the lambs’ jejunal microbiota. Clearly, an intensive MR feeding program induced a milder immunity response and lower relative abundance of pathogenic bacteria when compared with the traditional feeding program.