Departamento de Pediatría y Cirugía Infantil, Facultad de Medicina, Hospital Dr. Luis Calvo Mackenna, Universidad de Chile, Santiago, Chile.
Front Cell Infect Microbiol. 2018 Jun 21;8:190. doi: 10.3389/fcimb.2018.00190. eCollection 2018.
Compared to bovine formula (BF), breast milk (BM) has unique properties. In the newborn intestine, there is a homeostatic balance between the counterparts of the immune system, which allows a physiological inflammation, modulated by the gut microbiota. Many studies have attempted to understand the effect of BF vs. BM, and the changes in the gut microbiota, but few also focus on intestinal inflammation. We conducted a cohort study of newborn infants during their first 3 months. In stool samples taken at 1 and 3 months (timepoints T1 and T3), we quantified calprotectin, IL-8 and α1-antitrypsin by ELISA and we evaluated the expression of and β genes by RT-qPCR. To determine the microbiota composition, the 16S rRNA gene was amplified and sequenced using 454 pyrosequencing. Sequences were clustered into operational taxonomic units (OTUs). In total 15 BM and 10 BF infants were enrolled. In the BM group, we found calprotectin and α1-antitrypsin levels were significantly elevated at T3 compared to T1; no differences were found between T1 and T3 in the BF group. A comparison between the BM and BF groups showed that calprotectin levels at T1 were lower in the BM than the BF group; this difference was not observed at T3. For IL-8 levels, we found no differences between groups. A gene expression analysis of the and β genes showed that infants from the BF group at T1 have a significantly increased expression of these markers compared to the BM group. Gut microbiota analyses revealed that the phylum Bacteroidetes was higher in BM than BF, whereas Firmicutes were higher in BF. A redundancy analysis and ANOVA showed BM has a community structure statistically different to BF at T1 but not at T3. Compared to BF, BM at T1 showed a higher representation of , and . We found a basal state of inflammation in the infants' intestine based on inflammation markers. One month after birth, infants receiving BF exhibited higher levels of inflammation compared to BM.
与牛配方奶(BF)相比,母乳(BM)具有独特的特性。在新生儿肠道中,免疫系统的对应物之间存在着一种内稳态平衡,使肠道微生物群能够调节生理性炎症。许多研究试图了解 BF 与 BM 的差异以及肠道微生物群的变化,但很少关注肠道炎症。
我们对新生儿在出生后的前 3 个月进行了队列研究。在 1 个月和 3 个月(时间点 T1 和 T3)时的粪便样本中,我们通过 ELISA 定量测定了钙卫蛋白、IL-8 和 α1-抗胰蛋白酶,并通过 RT-qPCR 评估了和 β 基因的表达。为了确定微生物群落的组成,我们使用 454 焦磷酸测序扩增和测序 16S rRNA 基因。序列被聚类为操作分类单元(OTUs)。共纳入 15 名 BM 和 10 名 BF 婴儿。在 BM 组中,我们发现 T3 时钙卫蛋白和 α1-抗胰蛋白酶水平明显高于 T1;BF 组在 T1 和 T3 之间没有差异。BM 和 BF 组之间的比较显示,T1 时 BM 组的钙卫蛋白水平低于 BF 组;这种差异在 T3 时并未观察到。对于 IL-8 水平,我们没有发现组间差异。和 β 基因的基因表达分析表明,与 BM 组相比,T1 时 BF 组的这些标志物表达显著增加。肠道微生物群分析显示,厚壁菌门在 BM 中高于 BF,而梭菌在 BF 中高于 BM。冗余分析和 ANOVA 显示,与 BF 相比,T1 时 BM 的群落结构在统计学上有差异,但 T3 时则没有。与 BF 相比,T1 时 BM 显示出更高的、和 的代表性。
我们发现基于炎症标志物,婴儿肠道存在基础炎症状态。出生后一个月,接受 BF 的婴儿表现出比 BM 更高的炎症水平。