急性呼吸窘迫综合征新生儿肠道菌群特征及其对免疫功能的影响

Characteristics of intestinal flora and its effect on immune function in neonates with ARDS

目的研究急性呼吸窘迫综合征(ARDS)新生儿肠道菌群特征及其对免疫功能的影响。方法采用前瞻性研究方法,以我院2017年1月至2021年1月诊断的新生儿急性呼吸窘迫综合征患儿120例作为研究对象,其中轻度患儿39例,中度患儿45例,重度患儿36例,另选取同期出生的健康新生儿120例作为对照组,收集患儿的粪便样本并保存于厌氧菌稀释液,使用MRS琼脂培养基、KF琼脂培养基、马丁培养基检测肠道双歧杆菌、肠球菌、乳杆菌以及真杆菌的数量,比较各类患儿肠道菌群、免疫指标的差异。结果观察组患儿肠道双歧杆菌(t=16.217,P<0.001)、肠球菌(t=10.677,P<0.001)、乳杆菌(t=8.326,P<0.001)以及真杆菌(t=12.455,P<0.001)数量显著低于对照组。轻度组、中度组以及重度组患儿肠道双歧杆菌(F=13.069,P<0.001)、肠球菌(F=10.269,P<0.001)、乳杆菌(F=12.036,P<0.001)以及真杆菌(F=10.698,P<0.001)数量之间的差异有统计学意义。患儿出生后第10天肠道乳杆菌[(8.37±0.53)lg CFU/g]、双歧杆菌[(9.89±1.61)lg CFU/g]、肠球菌[(7.903±2.12)lg CFU/g]以及真杆菌[(7.12±1.29)lg CFU/g]数量显著低于出生后第20天时的肠道乳杆菌[(8.99±0.31)lg CFU/g]、双歧杆菌[(10.62±2.64)lg CFU/g]、肠球菌[(8.51±2.28)lg CFU/g]以及真杆菌[(7.91±1.01)lg CFU/g]数量(均P<0.05)。观察组患儿血清补体C3(t=14.183,P<0.001)、补体C4(t=9.002,P<0.001)、IgM(t=11.904,P<0.001)、IgG(t=147.674,P<0.001)水平显著低于对照组,而IgA(t=13.874,P<0.001)水平显著高于对照组。轻度组、中度组以及重度组患儿血清补体C3(F=11.369,P<0.001)、补体C4(F=10.396,P<0.001)、IgM(F=11.003,P<0.001)、IgG(F=9.663,P<0.001)、IgA(F=9.245,P<0.001)之间的差异均有统计学意义。C3、C4、IgM、IgG水平从高到低依次为轻度组、中度组以及重度组。IgA水平从高到低依次为重度组、中度组以及轻度组。肠道双歧杆菌、肠球菌、乳杆菌以及真杆菌与C3、C4、IgM、IgG水平呈正相关,与IgA水平呈负相关。结论ARDS新生儿肠道菌群与免疫功能具有显著相关性,未来可作为临床治疗的重要靶点之一。

Objective To interrogate the intestinal flora characteristics of newborns with acute respiratory distress syndrome(ARDS) and its influence on immune function. Methods This study adopted the prospective research method. A total of 120 newborns with ARDS diagnosed in our hospital from January 2017 to January 2021 were selected as the subjects, including 39 mild cases, 45 moderate cases, and 36 severe cases. Another 120 healthy newborns born in the same period were selected as the control group. The differences in the intestinal flora and immune indexes were compared among groups. Result The intestinal Bifidobacterium(t=16.217, P<0.001), Enterococcus(t=10.677, P<0.001), Lactobacillus(t=8.326, P<0.001) and Eubacterium(t=12.455, P<0.001) in the observation groups were significantly lower than those in the control group respectively. There were significant differences in the counts of Bifidobacterium(F=13.069, P<0.001), Enterococcus(F=10.269, P<0.001), Lactobacillus(F=12.036, P<0.001) and Eubacterium(F=10.698, P<0.001) among the mild group, moderate group, and severe group. The intestinal Lactobacillus [(8.37±0.53)lg CFU/g], Bifidobacterium [(9.89±1.61)lg CFU/g], Enterococcus [(7.903±2.12)lg CFU/g] and Genobacterium [(7.12±1.29)lg CFU/g] were detected at day 10 postnatal were significantly lower than those of intestinal Lactobacillus [(8.99±0.31)lg CFU/g], Bifidobacterium [(10.62±2.64)lg CFU/g], Enterococcus [(8.51±2.28)lg CFU/g] and Genobacterium [(7.91±1.01)lg CFU/g] on day 20, respectively. The levels of C3(t=14.183, P<0.001), C4(t=9.002, P<0.001), IgM(t=11.904, P<0.001) and IgG(t=147.674, P<0.001) in the observation groups were significantly lower than those in the control group respectively. The levels of IgA(t= 13.874, P<0.001) in the observation group were significantly higher than those in the control group. The levels of C3(F=11.369, P<0.001), C4(F=10.396, P<0.001), IgM(F=11.003, P<0.001), IgG(F=9. 663,P<0.001), IgA(F=9.245, P<0.001) were significantly different among groups. By pairwise comparison, the levels of C3, C4, IgM and IgG descended with the disease severity from mild, to moderate to severe, while that of IgA descended with the disease severity from severe, moderate to mild.The intestinal Lactobacillus and Enterococcus were positively correlated with C3, C4, IgM, and IgG, and negatively correlated with IgA. Conclusion There is a significant correlation between intestinal flora and immune function in newborns with ARDS, which can be used as one of the important targets for clinical treatment in the future.