①腸道代謝組學(xué)反映了各種暴露的生物學(xué)后果，并可能為哮喘的病理生理學(xué)研究提供線索。②在維生素D產(chǎn)前哮喘減輕試驗(yàn)(VDAART)的輔助研究中，對(duì)兒童哮喘的腸道代謝組學(xué)進(jìn)行非靶向的綜合分析。③采用質(zhì)譜法對(duì)361例3歲兒童糞便樣品進(jìn)行代謝組學(xué)分析。調(diào)整后的logistic回歸分析確定了3歲前與哮喘診斷高度相關(guān)的代謝物和代謝物模塊。稀疏典型相關(guān)分析確定了腸道代謝組與其他“組學(xué)”之間與哮喘相關(guān)性：16S rRNA測(cè)序測(cè)定的腸道微生物組、質(zhì)譜測(cè)定的血漿代謝組和食物頻率問卷測(cè)定的飲食結(jié)構(gòu)。3歲時(shí)，一些腸道代謝產(chǎn)物與哮喘相關(guān)，包括哮喘與多不飽和脂肪酸(校正后的logistic回歸β值為-6.3,95% CI -11.3， -1.4, p = 0.01)和其他脂類之間的負(fù)相關(guān)。哮喘相關(guān)腸代謝物是嬰兒出生前四個(gè)月純母乳喂養(yǎng)與哮喘負(fù)相關(guān)關(guān)系(p為間接相關(guān)= 0.04)和富含肉類的飲食與哮喘正相關(guān)關(guān)系(p = 0.03)的重要中介物。特定的腸道細(xì)菌類群，包括Christensenellaceae族，和血漿代謝物，包括-生育酚/β -生育酚，與哮喘和哮喘相關(guān)的腸道代謝物呈正相關(guān)。④綜合分析顯示，腸道代謝組與腸道微生物組、血漿代謝組和飲食與兒童哮喘有關(guān)。這些發(fā)現(xiàn)需要在未來加以重復(fù)研究。

延伸閱讀
JACI                                                             

Integrative Analysis of the Intestinal Metabolome of Childhood Asthma
https://doi.org/10.1016/j.jaci.2019.02.032
 Abstract:
Background
The intestinal metabolome reflects biological consequences of diverse exposures and may provide insight into asthma pathophysiology.
Objective
To perform an untargeted integrative analysis of the intestinal metabolome of childhood asthma in this ancillary study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART).
Methods
Metabolomic profiling was performed by mass spectrometry on fecal samples collected from 361 3-year-old subjects. Adjusted logistic regression analyses identified metabolites and modules of highly correlated metabolites associated with asthma diagnosis by age 3 years. Sparse canonical correlation analysis identified associations relevant to asthma between the intestinal metabolome and other “omics”: intestinal microbiome as measured by 16S rRNA sequencing, plasma metabolome as measured by mass spectrometry, and diet as measured by food frequency questionnaires.
Results
Several intestinal metabolites were associated with asthma at age 3 years, including inverse associations between asthma and polyunsaturated fatty acids (adjusted logistic regression beta = -6.3, 95% CI -11.3, -1.4, p = 0.01) and other lipids. Asthma-associated intestinal metabolites were significant mediators of the inverse relationship between exclusive breastfeeding for the first 4 months of life and asthma (p for indirect association = 0.04), and the positive association between a diet rich in meats and asthma (p = 0.03). Specific intestinal bacterial taxa, including family Christensenellaceae, and plasma metabolites, including gamma-tocopherol/beta-tocopherol, were positively associated with asthma and with asthma-associated intestinal metabolites.
Conclusion
Integrative analyses revealed significant interrelationships between the intestinal metabolome and the intestinal microbiome, plasma metabolome, and diet in association with childhood asthma. These findings require replication in future studies.
All Author:
Kathleen A.Lee-SarwarMD, MS12Rachel S.KellyPhD2JessicaLasky-SuScD2Robert S.ZeigerMD, PhD3George T.O’ConnorMD, MS4Megan T.SandelMD5Leonard B.BacharierMD6AvrahamBeigelmanMD, MSCI6NancyLaranjo2Diane R.GoldMD, MPH27Scott T.WeissMD, MS2 Augusto A.LitonjuaMD, MPH8

 2019-3-27 Article