Área Inmunología, Departamento de Biociencias (DEPBIO), Facultad de Química, Universidad de la República, Montevideo, Uruguay.
Unidad Asociada de Inmunología, Instituto de Química Biológica (IQB), Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
Front Immunol. 2023 Nov 8;14:1282144. doi: 10.3389/fimmu.2023.1282144. eCollection 2023.
The gastrointestinal and immune systems of premature infants are not fully developed, rendering them more vulnerable to severe complications like necrotizing enterocolitis. Human milk offers a rich array of bioactive factors that collectively contribute to reducing the incidence of gut infections and inflammatory conditions. When a mother's milk is unavailable, preterm infants are often provided with donor human milk processed in Human Milk Banks. However, it remains uncertain whether pasteurized milk confers the same level of risk reduction as unprocessed milk. This uncertainty may stem from the well-documented adverse effects of heat treatment on milk composition. Yet, our understanding of the comprehensive impact on protective mechanisms is limited.
In this study, we conducted a comparative analysis of the effects of raw versus pasteurized milk and colostrum versus mature milk on cellular functions associated with the gut epithelial barrier and responses to inflammatory stimuli. We utilized THP-1 and HT-29 cell lines, representing monocyte/macrophages and gut epithelial cells, respectively.
Our observations revealed that all milk types stimulated epithelial cell proliferation. However, only raw colostrum increased cell migration and interfered with the interaction between and epithelial cells. Furthermore, the response of epithelial and macrophage cells to lipopolysaccharide (LPS) was enhanced solely by raw colostrum, with a milder effect observed with mature milk. In contrast, both raw and pasteurized milk diminished the LPS induced response in monocytes. Lastly, we examined how milk affected the differentiation of monocytes into macrophages, finding that milk reduced the subsequent inflammatory response of macrophages to LPS.
Our study sheds light on the impact of human milk on certain mechanisms that potentially account for its protective effects against necrotizing enterocolitis, highlighting the detrimental influence of pasteurization on some of these mechanisms. Our findings emphasize the urgency of developing alternative pasteurization methods to better preserve milk properties. Moreover, identifying the key components critically affected by these protective mechanisms could enable their inclusion in donor milk or formula, thereby enhancing immunological benefits for vulnerable newborns.
早产儿的胃肠道和免疫系统尚未完全发育成熟，使他们更容易出现坏死性小肠结肠炎等严重并发症。母乳提供了丰富的生物活性因子，共同有助于降低肠道感染和炎症的发生率。当母亲的乳汁无法提供时，早产儿通常会接受人乳库处理的捐赠人乳。然而，目前还不确定巴氏消毒奶是否能降低与未加工奶相同的风险。这种不确定性可能源于热处理对牛奶成分的不良影响。然而，我们对其对保护机制的全面影响的了解有限。
在这项研究中，我们对生奶与巴氏消毒奶、初乳与成熟奶对与肠道上皮屏障相关的细胞功能和对炎症刺激的反应的影响进行了比较分析。我们使用了 THP-1 和 HT-29 细胞系，分别代表单核细胞/巨噬细胞和肠道上皮细胞。
我们的观察结果表明，所有类型的奶都能刺激上皮细胞增殖。然而，只有生初乳能增加细胞迁移并干扰与上皮细胞的相互作用。此外，上皮细胞和巨噬细胞对脂多糖（LPS）的反应仅由生初乳增强，而成熟奶则观察到较弱的反应。相反，生奶和巴氏消毒奶都能减弱单核细胞中 LPS 诱导的反应。最后，我们研究了奶如何影响单核细胞向巨噬细胞的分化，发现奶能降低巨噬细胞对 LPS 的后续炎症反应。
我们的研究揭示了人乳对某些机制的影响，这些机制可能解释了其对坏死性小肠结肠炎的保护作用，强调了巴氏消毒对其中一些机制的不利影响。我们的发现强调了迫切需要开发替代巴氏消毒方法，以更好地保留奶的特性。此外，确定受这些保护机制严重影响的关键成分，可能使它们能够包含在捐赠奶或配方奶中，从而为脆弱的新生儿增强免疫益处。
