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口服暴露于双酚类物质可通过调节成年小鼠的免疫反应,在体内诱导食物不耐受和结肠炎。

Oral exposure to bisphenols induced food intolerance and colitis in vivo by modulating immune response in adult mice.

机构信息

Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31300, Toulouse, France.

Hannover Medical School, Institute for Laboratory Animal Science, Carl-Neuberg-Str.1, 30625, Hannover, Germany.

出版信息

Food Chem Toxicol. 2020 Dec;146:111773. doi: 10.1016/j.fct.2020.111773. Epub 2020 Oct 1.

Abstract

Bisphenol (BP) A, a known food contaminant, is a possible risk factor in the epidemic of non-communicable diseases (NCD) including food intolerance and inflammatory bowel diseases (IBD). Regulatory restrictions regarding BPA usage led to BPA removal and replacement by poorly described substitutes, like BPS or BPF (few data on occurrence in food and human samples and biological effect). Oral tolerance protocol to ovalbumin (OVA) in WT mice and Il10 mice prone to IBD were used respectively to address immune responses towards food and microbial luminal antigens following BP oral exposure. Both mice models were orally exposed for five weeks to BPA, BPS or BPF at 0.5, 5 and 50 μg/kg of body weight (bw)/day (d). Oral exposure to BPs at low doses (0.5 and 5 μg/kg bw/d) impaired oral tolerance as indicated by higher humoral and pro-inflammatory cellular responses in OVA-tolerized mice. However, only BPF exacerbate colitis in Il10 prone mice associated with a defect of fecal IgA and increased secretion of TNF-α in colon. These findings provide a unique comparative study on effects of adult oral exposure to BPs on immune responses and its consequences on NCD related to intestinal luminal antigen development.

摘要

双酚 A(BP)是一种已知的食物污染物,可能是包括食物不耐受和炎症性肠病(IBD)在内的非传染性疾病(NCD)流行的一个风险因素。由于对 BPA 使用的监管限制,导致其被描述不佳的替代品(如 BPS 或 BPF)所取代,这些替代品在食物和人类样本中的存在情况和生物学效应数据很少。本研究使用卵清蛋白(OVA)在 WT 小鼠和易患 IBD 的 Il10 小鼠中的口服耐受方案,分别研究了 BP 口服暴露后对食物和微生物腔抗原的免疫反应。这两种小鼠模型均经口暴露于 0.5、5 和 50μg/kg 体重(bw)/天(d)的 BPA、BPS 或 BPF 中,为期五周。低剂量(0.5 和 5μg/kg bw/d)的 BP 口服暴露会损害口服耐受,这表现为在 OVA 耐受的小鼠中出现更高的体液和促炎细胞反应。然而,只有 BPF 会加剧 Il10 易感小鼠的结肠炎,这与粪便 IgA 缺陷和结肠中 TNF-α分泌增加有关。这些发现提供了一项关于成人经口暴露于 BP 对免疫反应及其对与肠道腔抗原发展相关的 NCD 影响的独特比较研究。

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