暴露于PM2.5浓缩的环境会改变小鼠模型中肠道微生物群的组成

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Exposure to concentrated ambient PM2.5 alters the composition of gut microbiota in a murine model

目的

暴露于环境细颗粒物(PM2.5)与葡萄糖体内平衡异常相关,但其潜在的生物学机制尚未完全了解。肠道微生物是葡萄糖代谢的稳态调节中新兴的关键参与者。很少有研究调查肠道微生物在PM2.5暴露诱导的葡萄糖平衡异常中的作用。

方  法

使用多用途气溶胶颗粒富集系统(VACES)将C57B1 / 6J小鼠暴露于过滤空气(FA)或浓缩的环境PM2.5(CAP)中达12个月,该系统经修改用于长期全身暴露。使用相关性和中介分析来对葡萄糖稳态和肠道微生物群检查和分析。

结  果

腹腔内葡萄糖耐量试验(IPGTT)和胰岛素耐量试验(ITT)显示CAP暴露显着地损害了葡萄糖和胰岛素耐受性。粪便微生物群分析表明,葡萄糖稳态受损与粪便细菌ACE和Chao-1估计值降低一致(社区丰富度指数),而所有粪便真菌α多样性估计值没有显着变化.Pearson相关分析表明,细菌丰富度估计值与葡萄糖和胰岛素耐受性相关,中介分析显示CAP暴露通过细菌Chao-1估计值的改变显著诱导葡萄糖不耐受。LEfSe分析揭示了CAP和FA暴露组间有24种细菌和21种真菌类群不同。其中,14种和20种细菌类群分别与IPGTT AUC和ITT AUC相关,5种真菌类群与葡萄糖代谢异常相关。

结  论

慢性暴露于PM2.5导致肠道菌群失调,并可能促成随后的葡萄糖代谢异常的发展。

原始文献摘要

Ing C, Sun M, Olfson M, et al. Age at Exposure to Surgery and Anesthesia in Children and Association With Mental Disorder Diagnosis.[J]. Anesthesia and analgesia,

 Abstract:

 BACKGROUND: Animals exposed to anesthetics during specific age periods of brain development experience neurotoxicity, with neurodevelopmental changes subsequently observed during adulthood. The corresponding vulnerable age in children, however, is unknown.

METHODS: An observational cohort study was performed using a longitudinal dataset constructed by linking individual-level Medicaid claims from Texas and New York from 1999 to 2010. This dataset was evaluated to determine whether the timing of exposure to anesthesia </=5 years of age for a single common procedure (pyloromyotomy, inguinal hernia, circumcision outside the perinatal period, or tonsillectomy and/or adenoidectomy) is associated with increased subsequent risk of diagnoses for any mental disorder, or specifically developmental delay (DD) such as reading and language disorders,  and attention deficit hyperactivity disorder (ADHD). Exposure to anesthesia and surgery was evaluated in 11 separate age at exposure categories: </=28 days old,  >28 days and </=6 months, >6 months and </=1 year, and 6-month age intervals between >1 year old and </=5 years old. For each exposed child, 5 children matched on propensity score calculated using sociodemographic and clinical covariates were selected for comparison. Cox proportional hazards models were used to measure the hazard ratio of a mental disorder diagnosis associated with exposure to surgery and anesthesia.

RESULTS: A total of 38,493 children with a single exposure and 192,465 propensity score-matched children unexposed before 5  years of age were included in the analysis. Increased risk of mental disorder diagnosis was observed at all ages at exposure with an overall hazard ratio of 1.26 (95% confidence interval [CI], 1.22-1.30), which did not vary significantly  with the timing of exposure. Analysis of DD and ADHD showed similar results, with elevated hazard ratios distributed evenly across all ages, and overall hazard ratios of 1.26 (95% CI, 1.20-1.32) for DD and 1.31 (95% CI, 1.25-1.37) for ADHD.

CONCLUSIONS: Children who undergo minor surgery requiring anesthesia under age 5  have a small but statistically significant increased risk of mental disorder diagnoses and DD and ADHD diagnoses, but the timing of the surgical procedure does not alter the elevated risks. Based on these findings, there is little support for the concept of delaying a minor procedure to reduce long-term neurodevelopmental risks of anesthesia in children. In evaluating the influence of age at exposure, the types of procedures included may need to be considered, as some procedures are associated with specific comorbid conditions and are only  performed at certain ages.

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