Arkansas Children's Nutrition Center, Little Rock, AR.
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR.
J Nutr. 2018 Nov 1;148(11):1860-1870. doi: 10.1093/jn/nxy170.
The benefits of breastfeeding infants are well characterized, including those on the immune system. However, determining the mechanism by which human breast milk (HBM) elicits effects on immune response requires investigation in an appropriate animal model.
The primary aim of this study was to develop a novel porcine model and to determine the differential effects of feeding HBM and a commercial milk formula (MF) on immune response and gastrointestinal microbial colonization in a controlled environment.
Male piglets were fed HBM (n = 26) or MF (n = 26) from day 2 through day 21. Piglets were vaccinated (n = 9/diet group) with cholera toxin and cholera toxin subunit B (CTB) and tetanus toxoid at 21 d or were fed placebo (n = 6/diet group) and then weaned to a standard solid diet at the age of 21 d. Humoral and cell-mediated immune responses were assessed from blood on days 35 and 48. Immune response was further examined from tissues, including mesenteric lymph nodes (MLNs), Peyer's patches (PPs), and spleen. The colonization of gut microbiota was characterized from feces on days 16 and 49.
Serum antibody titers in piglets fed HBM were 4-fold higher (P < 0.05) to CTB and 3-fold higher (P < 0.05) to tetanus toxoid compared with piglets fed MF on day 48. Compared with MF, the numbers of immunoglobulin A antibody-producing cells to CTB were 13-fold higher (P < 0.05) in MLNs and 11-fold higher (P < 0.05) in PPs in the HBM diet group on day 51. In addition, significantly increased T cell proliferation was observed in the HBM group relative to the MF group. Furthermore, microbial diversity in the HBM group was lower (P < 0.05) than in the MF group.
This porcine model appears to be valid for studying the effects of early postnatal diet on immune responses and the gastrointestinal microbiome. Our results lay the groundwork for future studies defining the role of infant diet on microbiota and immune function.
母乳喂养婴儿的益处已得到充分证实，包括对免疫系统的益处。然而，要确定人乳（HBM）对免疫反应产生影响的机制，需要在适当的动物模型中进行研究。
本研究的主要目的是建立一种新的猪模型，并确定在受控环境下，喂养 HBM 和商业配方奶（MF）对免疫反应和胃肠道微生物定植的差异影响。
雄性仔猪从第 2 天到第 21 天分别用 HBM（n=26）或 MF（n=26）喂养。在第 21 天，仔猪用霍乱毒素和霍乱毒素亚单位 B（CTB）和破伤风类毒素接种疫苗（n=9/饮食组），或用安慰剂喂养（n=6/饮食组），然后在 21 天大时断奶为标准固体饮食。在第 35 天和第 48 天从血液中评估体液和细胞介导的免疫反应。进一步从肠系膜淋巴结（MLNs）、派尔集合淋巴结（PPs）和脾脏等组织中检查免疫反应。在第 16 天和第 49 天从粪便中描述肠道微生物群的定植情况。
与用 MF 喂养的仔猪相比，用 HBM 喂养的仔猪在第 48 天对 CTB 的血清抗体滴度高 4 倍（P<0.05），对破伤风类毒素的血清抗体滴度高 3 倍（P<0.05）。与 MF 相比，在 HBM 饮食组中，第 51 天 CTB 免疫球蛋白 A 抗体产生细胞的数量在 MLNs 中高 13 倍（P<0.05），在 PPs 中高 11 倍（P<0.05）。此外，与 MF 组相比，HBM 组的 T 细胞增殖明显增加。此外，HBM 组的微生物多样性低于 MF 组（P<0.05）。
该猪模型似乎适用于研究早期产后饮食对免疫反应和胃肠道微生物组的影响。我们的研究结果为未来研究确定婴儿饮食对微生物组和免疫功能的作用奠定了基础。
