出生前對羥基苯甲酸酯暴露與兒童肥胖及其腸道菌相組成之相關性探討

Prenatal exposure to parabens in relation to childhood obesity and the gut microbiome

目標：對羥基苯甲酸酯（Parabens, PB）作為常見防腐劑也具有干擾內分泌的特性。過去研究指出產前PB的暴露會干擾人體內分泌和代謝信號並可能會對健康造成長期的影響。本研究欲探討孕婦PB暴露對孩童過重與其腸道菌分布的影響。方法：納入台灣婦幼世代研究（TMICS）在中部地區的284組母子。以液相層析串聯式質譜儀（LC-MS/MS）檢測孕婦尿中四種常見的PB，包括對羥基苯甲酸甲酯、對羥基苯甲酸乙酯、對羥基苯甲酸丙酯、對羥基苯甲酸丁酯。將98位兒童的糞便樣本以總基因體定序法（shotgun metagenomics sequencing）獲得腸道菌的組成和相對豐度，再分析產前PB暴露與兒童成長及腸道菌相之相關性。結果：產前PB暴露增加，觀察到男童的身高顯著降低，胸圍則較寬，而女童的BMI則較高。在腸道菌部分，顯著減少了分解多醣、纖維等有益物種的豐度，如Barnesiella spp、Bacteroides uniformis和Eubacterium rectale。相反地，伺機性菌種明顯增加，並干擾了能量攝入的調節。結論：產前PB對出生至學齡前兒童具潛在的致肥胖性，並影響其腸道菌叢的分布，而對於在青春期後成長情形的影響與腸道菌相組成的變化，待進一步研究做驗證。

Objectives: Parabens, which are common antimicrobial preservatives, are considered to be endocrine-disrupting chemicals. Previous studies regarding maternal exposure to paraben have shown that disturbances in physiological endocrine and metabolic signals during early childhood may lead to the long-term adverse health effects in children. We investigated the effects of maternal exposure to paraben on childhood obesity and gut microbiome diversity. Methods: We collected the data on 284 maternalinfant pairs from the central region of Taiwan Maternal- Infant Cohort Study. Liquid chromatography-tandem mass spectrometry was used to detect 4 common parabens, including methyl-paraben, ethyl-paraben, propyl-paraben, and butyl-paraben in maternal urinary samples. In addition, shotgun metagenomics sequencing was used to analyze 98 children’s fecal samples. Results: Greater maternal exposure to paraben was observed in boys who were significantly shorter and with wider chest circumferences and in girls with higher body mass index. Increased maternal exposure to paraben significantly reduced the abundance of several species, such as Barnesiella, Bacteroides uniformis, and Eubacterium rectale, but increased the abundance of several opportunistic pathogens, which interfered with the regulation of energy consumption. Conclusions: Maternal exposure to paraben promoted the development of obesity in girls and disrupted the diversity of gut microbial community. Maternal exposure to paraben may promote obesity in children at preschooler age. In addition, additional studies on the effects of the composition of the gut microbiome after puberty are required.