早产儿肠道菌群变化及其与新生儿感染的相关性

Changes of intestinal flora in premature infants and its correlation with neonatal infection

目的研究早产儿肠道菌群变化并分析其与新生儿感染的相关性。方法前瞻性选取2020年1月至2022年1月西安大兴医院新生儿科收治的80例早产儿,所有早产儿均在纠正胎龄40周时进行早产儿肠道菌群及感染检测,根据早产儿是否发生感染分为感染组26例和非感染组54例,比较两组早产儿的肠道菌群丰度、菌群物种丰富度(Chaol指数)、菌群群落多样性(Shannon指数)的差异,采用多因素Logistic回归分析早产儿发生感染的影响因素,采用Pearson相关分析法分析早产儿感染与肠道菌群变化的关系。结果感染组早产儿的白细胞(WBC)、C反应蛋白(CRP)、降钙素原(PCT)水平分别为(16.77±3.20)×10^(9)/L、(17.65±4.41)mg/L、(3.82±0.55)ng/mL,明显高于非感染组的(11.18±3.42)×10^(9)/L、(4.93±1.19)mg/L、(0.35±0.08)ng/mL,而新生儿危重病例评分(NCIS)为(86.46±4.23)分,明显低于非感染组的(93.36±4.50)分,差异均有统计学意义(P<0.05);感染组早产儿的感染性肺炎发生率、呼吸衰竭发生率和败血症发生率分别为73.08%、57.69%、34.62%,明显高于非感染组的46.30%、31.48%、5.56%,差异均有统计学意义(P<0.05);感染组早产儿的双歧杆菌属、乳杆菌属、乳球菌属、拟杆菌属的丰度分别为(23.65±1.26)%、(16.60±0.95)%、(15.72±0.90)%、(8.88±0.65)%,明显低于对照组的(29.03±1.36)%、(22.45±1.28)%、(17.81±1.11)%、(9.78±0.68)%,差异均有统计学意义(P<0.05);感染组早产儿的链球菌属、沙门菌属、瓦氏菌属、梭菌属、葡萄球菌属丰度分别为(12.92±0.82)%、(5.75±0.55)%、(4.85±0.30)%、(6.76±0.56)%、(8.51±0.64)%,明显高于非感染组的(5.82±0.36)%、(4.27±0.33)%、(3.95±0.21)%、(2.20±0.18)%、(1.97±0.16)%,差异均有统计学意义(P<0.05);感染组早产儿的Chaol指数及Shannon指数分别为284.46±17.78、2.73±0.35,明显低于非感染组的395.52±21.60、3.99±0.48,差异均有统计学意义(P<0.05);经多因素Logistic回归分析结果显示,双歧杆菌属、Chaol指数、Shannon指数是早产儿感染发生的保护性因素(P<0.05);链球菌属、沙门菌属、葡萄球菌属是早产儿感染发生的危险因素(P<0.05);经Pearson相关分析法分析结果显示,早产儿NCIS评分与双歧杆菌属丰度比(r=0.652)、乳杆菌属丰度比(r=0.589)、去球菌属丰度比(r=0.618)、拟杆菌属丰度比(r=0.602)、Chaol指数(r=0.547)、Shonnon指数(r=0.551)呈正相关(P<0.05),与链球菌属丰度比(r=-0.524)、沙门菌属丰度比(r=-0.611)、瓦氏菌属丰度比(r=-0.514)、梭菌属丰度比(r=-0.531)、葡萄球菌属丰度比(r=-0.529)呈负相关(P<0.05)。结论早产儿较正常健康新生儿更易发生感染性疾病。感染早产儿存在明显的肠道菌群失衡,菌群物种丰富度、菌群群落多样性均降低,且菌群变化与感染性疾病的发生发展存在明显相关性。

Objective To study the changes of intestinal flora in premature infants and analyze its correlation with neonatal infection.Methods Eighty premature infants who were treated in Department of Neonatology,Xi’an Daxing Hospital were prospectively selected between January 2020 and January 2022.All premature infants were tested for intestinal flora and infection at the corrected gestational age of 40 weeks.According to whether infection occurred in premature infants,they were divided into infection group(26 cases)and non-infection group(54 cases).The differences in intestinal flora abundance,flora species richness(Chaol index),and flora diversity(Shannon index)were compared between the two groups of premature infants.Multivariate Logistic regression analysis was used to analyze the influencing factors of infection in premature infants,and Pearson correlation analysis was applied to analyze the relationship between infection and intestinal flora changes in premature infants.Results The white blood cell(WBC),C-reactive protein(CRP),and procalcitonin(PCT)were(16.77±3.20)×10^(9)/L,(17.65±4.41)mg/L,and(3.82±0.55)ng/mL in infection group,significantly higher than(11.18±3.42)×10^(9)/L,(4.93±1.19)mg/L,and(0.35±0.08)ng/mL in non-infection group;the neonatal critical illness score(NCIS)was(86.46±4.23)points,significantly lower than(93.36±4.50)points in non-infection group;the differences were statistically significant(P<0.05).The incidence rates of infectious pneumonia,respiratory failure,and sepsis were 73.08%,57.69%,and 34.62% in infection group,significantly higher than 46.30%,31.48%,and 5.56% in non-infection group(P<0.05).The abundance of Bifidobacterium,Lactobacillus,Lactococcus,and Bacteroides were(23.65±1.26)%,(16.60±0.95)%,(15.72±0.90)%,and(8.88±0.65)%in infection group,significantly lower than(29.03±1.36)%,(22.45±1.28)%,(17.81±1.11)%,and(9.78±0.68)%in non-infection group(P<0.05).The abundance of Streptococcus,Salmonella,Shewanella,Clostridium,and Staphylococcus were(12.92±0.82)%,(5.75±0.55)%,(4.85±0.30)%,(6.76±0.56)%,and(8.51±0.64)% in infection group,significantly higher than(5.82±0.36)%,(4.27±0.33)%,(3.95±0.21)%,(2.20±0.18)%,and(1.97±0.16)% in non-infection group(P<0.05).The Chaol index and Shannon index were 284.46±17.78 and 2.73±0.35 in infection group,significantly lower than 395.52±21.60 and 3.99±0.48 in non-infection group(P<0.05).Multivariate Logistic regression analysis showed that Bifidobacterium,Chaol index,and Shannon index were protective factors for infection occurrence in premature infants(P<0.05).Streptococcus,Salmonella,and Staphylococcus were risk factors for infection in premature infants(P<0.05).Pearson correlation analysis revealed that NCIS score in premature infants was positively correlated with Bifidobacterium abundance ratio(r=0.652),Lactobacillus abundance ratio(r=0.589),Lactococcus abundance ratio(r=0.618),Bacteroides abundance ratio(r=0.602),Chaol index(r=0.547),and Shonnon index(r=0.551)(P<0.05),and was negatively correlated with Streptococcus abundance ratio(r=-0.524),Salmonella abundance ratio(r=-0.611),Shewanella abundance ratio(r=-0.514),Clostridium abundance ratio(r=-0.531),and Staphylococcus abundance ratio(r=-0.529)(P<0.05).Conclusion Premature infants are more likely to develop infectious diseases than normal healthy neonates.The intestinal flora in infected premature infants is obviously imbalanced and the flora species richness and flora diversity are reduced,and the change of flora is significantly correlated with the occurrence and development of infectious diseases.