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Abstract：
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.
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.
摘要：
背景：断奶前代乳品（MR）喂养计划是影响羔羊断奶期间健康和福利的关键因素。众所周知，断奶压力是一种对反刍动物的免疫系统产生负面影响的诱因，其生理和免疫状态与肠道中的微生物群落密切相关。这项研究有两个目的：1）在生理和分子水平上评估对断奶应激的先天免疫反应；2）研究MR对照组和高平面之间空肠食糜和粘膜粘附微生物群的变化。
结果：在本实验中，血浆皮质醇的浓度，去甲肾上腺素（NE）和肿瘤坏死因子-α（TNFα）在C组高于H组（P<0.05），血浆中TNFα和CXCL8等促炎细胞因子的表达（P<0.05）。在空肠组织中，C组TLR4和TNFα的表达也较高（P<0.01）；组织病理学显示H组淋巴细胞浸润较低。在C组中,然而,主要病理变化与淋巴细胞广泛浸润有关，嗜酸性粒细胞,和中性粒细胞。主成分分析表明，羔羊的免疫反应受断奶应激的影响，并受MR处理的调节。使用16S-rRNA测序来评估空肠粘膜和食糜细菌的多样性和组成。C组食糜的α指数（ACE：P=0.095；Chao1：P=0.085）高于H组。在空肠粘膜，C组Plesiomonas的相对丰度比H组高4倍（P=0.017）。
结论：这项研究的结果表明，断奶压力引起羔羊免疫系统的改变，持续时间超过21天，并且通过其血液学和表达的促炎细胞因子的变化证明了长期的炎症反应作用。断奶前MR余量不同会导致复杂的生物学反应和羔羊空肠微生物群的组成变化。显然,与传统的喂养计划相比，强化的MR喂养计划诱导了更温和的免疫反应和更低的病原菌相对丰度。
结果：在本实验中，血浆皮质醇的浓度，去甲肾上腺素（NE）和肿瘤坏死因子-α（TNFα）在C组高于H组（P<0.05），血浆中TNFα和CXCL8等促炎细胞因子的表达（P<0.05）。在空肠组织中，C组TLR4和TNFα的表达也较高（P<0.01）；组织病理学显示H组淋巴细胞浸润较低。在C组中,然而,主要病理变化与淋巴细胞广泛浸润有关，嗜酸性粒细胞,和中性粒细胞。主成分分析表明，羔羊的免疫反应受断奶应激的影响，并受MR处理的调节。使用16S-rRNA测序来评估空肠粘膜和食糜细菌的多样性和组成。C组食糜的α指数（ACE：P=0.095；Chao1：P=0.085）高于H组。在空肠粘膜，C组Plesiomonas的相对丰度比H组高4倍（P=0.017）。
结论：这项研究的结果表明，断奶压力引起羔羊免疫系统的改变，持续时间超过21天，并且通过其血液学和表达的促炎细胞因子的变化证明了长期的炎症反应作用。断奶前MR余量不同会导致复杂的生物学反应和羔羊空肠微生物群的组成变化。显然,与传统的喂养计划相比，强化的MR喂养计划诱导了更温和的免疫反应和更低的病原菌相对丰度。
