Bisphenol-A alters microbiota metabolites derived from aromatic amino acids and worsens disease activity during colitis
Bisphenol-A alters microbiota metabolites derived from aromatic amino acids and worsens disease activity during colitis
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DOI：
10.1177/1535370218782139
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发表时间：
2018-06-01
影响因子：
3.2
通讯作者：
Allred, Clinton D.
中科院分区：
文献类型：
--
作者：
DeLuca, Jennifer A. A.;Allred, Kimberly F.;Allred, Clinton D.
炎症性肠病是一种复杂的疾病集合。微生物生态失调以及暴露于毒素包括异种雌激素被认为是炎症性肠病发展和复发的风险因素。双酚-A已被证明在结肠中发挥雌激素活性并改变肠功能，但异种雌激素（如双酚-A）在结肠炎症中发挥的作用先前已有描述，但结果相互矛盾。我们研究了双酚A在急性葡聚糖硫酸钠诱导的结肠炎模型中加剧结肠炎症和改变源自芳香族氨基酸的微生物群代谢物的能力。切除雌性C57 BL/6小鼠卵巢，每天暴露于双酚A，持续15天。疾病活动性测量包括体重、粪便稠度和直肠出血。对结肠的炎症、损伤和结节进行评分。分析了已知反映肠道微生物组表型变化的源自芳香族氨基酸的微生物群代谢物水平的变化。双酚A暴露增加死亡率和恶化的疾病活动性，以及炎症和结节评分在中结肠区域后，葡聚糖硫酸钠暴露。独特的模式的代谢产物与双酚A的消费。无论硫酸葡聚糖钠治疗，双酚A降低色氨酸和几种代谢物的水平，减少结肠炎症。这是第一项研究表明，双酚A单独治疗可以减少结肠中芳香族氨基酸衍生的微生物群代谢物，这可能与结肠炎症和炎症性肠病增加有关。
Inflammatory bowel disease is a complex collection of disorders. Microbial dysbiosis as well as exposure to toxins including xenoestrogens are thought to be risk factors for inflammatory bowel disease development and relapse. Bisphenol-A has been shown to exert estrogenic activity in the colon and alter intestinal function, but the role that xenoestrogens, such as bisphenol-A , play in colonic inflammation has been previously described but with conflicting results. We investigated the ability of bisphenol-A to exacerbate colonic inflammation and alter microbiota metabolites derived from aromatic amino acids in an acute dextran sulfate sodium-induced colitis model. Female C57BL/6 mice were ovariectomized and exposed to bisphenol-A daily for 15 days. Disease activity measures include body weight, fecal consistency, and rectal bleeding. Colons were scored for inflammation, injury, and nodularity. Alterations in the levels of microbiota metabolites derived from aromatic amino acids known to reflect phenotypic changes in the gut microbiome were analyzed. Bisphenol-A exposure increased mortality and worsened disease activity as well as inflammation and nodularity scores in the middle colon region following dextran sulfate sodium exposure. Unique patterns of metabolites were associated with bisphenol-A consumption. Regardless of dextran sulfate sodium treatment, bisphenol-A reduced levels of tryptophan and several metabolites associated with decreased inflammation in the colon. This is the first study to show that bisphenol-A treatment alone can reduce microbiota metabolites derived from aromatic amino acids in the colon which may be associated with increased colonic inflammation and inflammatory bowel disease.