剖宫产新生儿代谢与儿童哮喘风险
2021/12/24
摘要
背景：剖宫产(CS)分娩与哮喘发生风险增加有关，但其潜在机制尚不清楚。
目的：利用新生儿代谢组学特征，结合早期肠道微生物群数据和脐血免疫学，阐明剖宫产分娩与哮喘之间的联系。
方法：我们研究了CS对哥本哈根两个独立儿童哮喘的前瞻性研究队列（即COPSAC2010（n=677）和 COPSAC2000（n =387））新生儿干血斑的液相色谱-质谱（LC-MS）代谢谱的影响。评估了 CS 代谢特征、一周龄肠道微生物组数据和脐带血 Treg 频率之间的关联。
结果：在COPSAC2010队列中，偏最小二乘判别分析(PLS-DA)模型显示，CS分娩和自然分娩的孩子具有不同的代谢特征(AUC=0.77，p=2.2e-16)，COPSAC2000队列中也有同样的结果(AUC=0.66，p=1.2e-5)。在COPSAC2010(p=0.03)和COPSAC2000(p=0.005)中，CS的代谢特征与学龄期哮喘风险增加呈显著相关。CS与色氨酸、胆汁酸和苯丙氨酸代谢物的丰度较低有关，表明肠道微生物群紊乱。此外，自然分娩后的优势肠道细菌，即双歧杆菌和类杆菌，与CS识别的微生物代谢物相关，表明分娩期间的母体微生物传播调节着新生儿的新陈代谢。最后，CS的代谢特征与脐带血Tregs的频率相关。
结论：这些发现表明在新生儿出生时CS通过扰乱免疫反应和血液代谢物中反映肠道微生物定植模式来规划儿童哮喘的风险。
Neonatal metabolome of cesarean section and risk of childhood asthma
Gözde Gürdeniz, Madeleine Ernst, Daniela Rago, Min Kim, Julie Courraud, Jakob Stokholm, Klaus Bønnelykke, Anders Björkbom, Urvish Trivedi, Søren J Sørensen, Susanne Brix, David Hougaard, Morten Rasmussen, Arieh S Cohen, Hans Bisgaard, Bo Chawes
Abstract
BACKGROUND： Birth by cesarean section (CS) is linked to an increased risk of developing asthma, but the underlying mechanisms are unclear.
OBJECTIVE: To elucidate the link between birth by CS and asthma using newborn metabolomic profiles and integrating early life gut microbiome data and cord blood immunology.
METHODS: We investigated the influence of CS on liquid chromatography mass spectrometry (LC-MS) metabolomic profiles of dried blood spots from newborns of the two independent Copenhagen Prospective Studies on Asthma in Childhood cohorts, i.e. COPSAC2010 (n=677) and COPSAC2000 (n=387). We assessed the associations between the CS metabolic profile, age one-week gut microbiome data and frequency of cord blood Tregs.
RESULTS: In COPSAC2010, a partial least square-discriminant analysis (PLS-DA) model showed that children born by CS versus natural delivery had different metabolic profiles (AUC=0.77, p=2.2e-16), which was replicated in COPSAC2000 (AUC=0.66, p=1.2e-5). The metabolic profile of CS was significantly associated with an increased risk of asthma at school-age in both COPSAC2010 (p=0.03) and COPSAC2000 (p=0.005). CS was associated with lower abundance of tryptophan, bile acid and phenylalanine metabolites, indicative of a perturbed gut microbiota. Further, gut bacteria dominating after natural delivery, i.e. Bifidobacterium and Bacteroides were correlated with CS-discriminative microbial metabolites, suggesting maternal microbial transmission during birth regulating the newborn's metabolism. Finally, the CS metabolic profile was associated with frequency of cord blood Tregs.
CONCLUSIONS: These findings propose that CS is programming the risk of childhood asthma through perturbed immune responses and gut microbial colonization patterns reflected in the blood metabolome at birth.
背景：剖宫产(CS)分娩与哮喘发生风险增加有关，但其潜在机制尚不清楚。
目的：利用新生儿代谢组学特征，结合早期肠道微生物群数据和脐血免疫学，阐明剖宫产分娩与哮喘之间的联系。
方法：我们研究了CS对哥本哈根两个独立儿童哮喘的前瞻性研究队列（即COPSAC2010（n=677）和 COPSAC2000（n =387））新生儿干血斑的液相色谱-质谱（LC-MS）代谢谱的影响。评估了 CS 代谢特征、一周龄肠道微生物组数据和脐带血 Treg 频率之间的关联。
结果：在COPSAC2010队列中，偏最小二乘判别分析(PLS-DA)模型显示，CS分娩和自然分娩的孩子具有不同的代谢特征(AUC=0.77，p=2.2e-16)，COPSAC2000队列中也有同样的结果(AUC=0.66，p=1.2e-5)。在COPSAC2010(p=0.03)和COPSAC2000(p=0.005)中，CS的代谢特征与学龄期哮喘风险增加呈显著相关。CS与色氨酸、胆汁酸和苯丙氨酸代谢物的丰度较低有关，表明肠道微生物群紊乱。此外，自然分娩后的优势肠道细菌，即双歧杆菌和类杆菌，与CS识别的微生物代谢物相关，表明分娩期间的母体微生物传播调节着新生儿的新陈代谢。最后，CS的代谢特征与脐带血Tregs的频率相关。
结论：这些发现表明在新生儿出生时CS通过扰乱免疫反应和血液代谢物中反映肠道微生物定植模式来规划儿童哮喘的风险。
(中日友好医院呼吸与危重症医学科 王静茹 摘译 林江涛 审校)
(Eur Respir J. 2021 Dec 9;2102406. doi: 10.1183/13993003.02406-2021.)
(Eur Respir J. 2021 Dec 9;2102406. doi: 10.1183/13993003.02406-2021.)
Neonatal metabolome of cesarean section and risk of childhood asthma
Gözde Gürdeniz, Madeleine Ernst, Daniela Rago, Min Kim, Julie Courraud, Jakob Stokholm, Klaus Bønnelykke, Anders Björkbom, Urvish Trivedi, Søren J Sørensen, Susanne Brix, David Hougaard, Morten Rasmussen, Arieh S Cohen, Hans Bisgaard, Bo Chawes
Abstract
BACKGROUND： Birth by cesarean section (CS) is linked to an increased risk of developing asthma, but the underlying mechanisms are unclear.
OBJECTIVE: To elucidate the link between birth by CS and asthma using newborn metabolomic profiles and integrating early life gut microbiome data and cord blood immunology.
METHODS: We investigated the influence of CS on liquid chromatography mass spectrometry (LC-MS) metabolomic profiles of dried blood spots from newborns of the two independent Copenhagen Prospective Studies on Asthma in Childhood cohorts, i.e. COPSAC2010 (n=677) and COPSAC2000 (n=387). We assessed the associations between the CS metabolic profile, age one-week gut microbiome data and frequency of cord blood Tregs.
RESULTS: In COPSAC2010, a partial least square-discriminant analysis (PLS-DA) model showed that children born by CS versus natural delivery had different metabolic profiles (AUC=0.77, p=2.2e-16), which was replicated in COPSAC2000 (AUC=0.66, p=1.2e-5). The metabolic profile of CS was significantly associated with an increased risk of asthma at school-age in both COPSAC2010 (p=0.03) and COPSAC2000 (p=0.005). CS was associated with lower abundance of tryptophan, bile acid and phenylalanine metabolites, indicative of a perturbed gut microbiota. Further, gut bacteria dominating after natural delivery, i.e. Bifidobacterium and Bacteroides were correlated with CS-discriminative microbial metabolites, suggesting maternal microbial transmission during birth regulating the newborn's metabolism. Finally, the CS metabolic profile was associated with frequency of cord blood Tregs.
CONCLUSIONS: These findings propose that CS is programming the risk of childhood asthma through perturbed immune responses and gut microbial colonization patterns reflected in the blood metabolome at birth.
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嗜酸性粒细胞在气道壁中的分布对于哮喘气道高反应性和T2炎症的特定特征至关重要
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靶向P2Y13受体抑制IL-33和HMGB1的释放并改善实验性哮喘
