牛奶蛋白过敏婴儿肠道菌群特异性变化及短链脂肪酸水平分析

Specific changes in gut microbiota and short-chain fatty acid levels in infants with cow's milk protein allergy

摘要:

目的 探索牛奶蛋白过敏（cow's milk protein allergy, CMPA）患儿肠道菌群及短链脂肪酸水平的变化，明确其在CMPA中的作用。方法 纳入2019年8月—2020年8月在郑州大学附属儿童医院就诊的25例CMPA婴儿作为CMPA组，同时选取25例正常婴儿作为对照组。收集两组婴儿粪便200 mg，采用16S rDNA高通量检测技术和液相色谱质谱联用技术分别检测肠道微生物组成及其代谢产物的变化，并将微生物多样性与代谢产物进行联合分析。结果 与对照组相比，CMPA组患儿肠道菌群结构发生变化，且α-多样性显著增加（P<0.001）。与对照组相比，CMPA组患儿肠道内厚壁菌门、梭状芽孢杆菌目、拟杆菌丰度显著降低，而梭菌科、支原体科、鞘脂单胞菌科丰度显著增加（P<0.001）。代谢组学检测发现，与对照组相比，CMPA组菌群代谢产物乙酸、丁酸和异戊酸水平显著下降，并与短链脂肪酸产生菌粪杆菌属、罗氏菌属等丰度呈正相关（P<0.05）。结论 CMPA患儿肠道内菌群结构发生改变，微生物多样性增加，短链脂肪酸水平降低，可能导致肠道炎症反应增加。

Abstract:

Objective To explore the changes in gut microbiota and levels of short-chain fatty acids (SCFA) in infants with cow's milk protein allergy (CMPA), and to clarify their role in CMPA.Methods A total of 25 infants diagnosed with CMPA at Children's Hospital Affiliated to Zhengzhou University from August 2019 to August 2020 were enrolled as the CMPA group, and 25 healthy infants were selected as the control group. Fecal samples (200 mg) were collected from both groups and subjected to 16S rDNA high-throughput sequencing technology and liquid chromatography-mass spectrometry to analyze the changes in gut microbial composition and metabolites. Microbial diversity was analyzed in conjunction with metabolites.Results Compared to the control group, the CMPA group showed altered gut microbial structure and significantly increased α-diversity (P<0.001). The abundance of Firmicutes, Clostridiales and Bacteroidetes was significantly decreased, while the abundance of Sphingomonadaceae, Clostridiaceae_1 and Mycoplasmataceae was significantly increased in the CMPA group compared to the control group (P<0.001). Metabolomic analysis revealed reduced levels of acetic acid, butyric acid, and isovaleric acid in the CMPA group compared to the control group, and the levels of the metabolites were positively correlated with the abundance of SCFA-producing bacteria such as Faecalibacterium and Roseburia (P<0.05).Conclusions CMPA infants have alterations in gut microbial structure, increased microbial diversity, and decreased levels of SCFA, which may contribute to increased intestinal inflammation.