Background & Aims

Separation of newborn rats from their mothers induces visceral hypersensitivity and impaired epithelial secretory cell lineages when they are adults. Little is known about the mechanisms by which maternal separation causes visceral hypersensitivity or its relationship with defects in epithelial secretory cell lineages.

Methods

We performed studies with C3H/HeN mice separated from their mothers as newborns and mice genetically engineered (Sox9^flox/flox-vil-cre on C57BL/6 background) to have deficiencies in Paneth cells. Paneth cell deficiency was assessed by lysozyme staining of ileum tissues and lysozyme activity in fecal samples. When mice were 50 days old, their abdominal response to colorectal distension was assessed by electromyography. Fecal samples were collected and microbiota were analyzed using Gut Low-Density Array quantitative polymerase chain reaction.

Results

Mice with maternal separation developed visceral hypersensitivity and defects in Paneth cells, as reported from rats, compared with mice without maternal separation. Sox9^flox/flox-vil-Cre mice also had increased visceral hypersensitivity compared with control littermate Sox9^flox/flox mice. Fecal samples from mice with maternal separation and from Sox9^flox/flox-vil-cre mice had evidence for intestinal dysbiosis of the microbiota, characterized by expansion of Escherichia coli. Daily gavage of conventional C3H/HeN adult mice with 10⁹ commensal E coli induced visceral hypersensitivity. Conversely, daily oral administration of lysozyme prevented expansion of E coli during maternal separation and visceral hypersensitivity.

Conclusions

Mice with defects in Paneth cells (induced by maternal separation or genetically engineered) have intestinal expansion of E coli leading to visceral hypersensitivity. These findings provide evidence that Paneth cell function and intestinal dysbiosis are involved in visceral sensitivity.

中文翻译：

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Paneth细胞缺陷诱导小鼠微生物群失调并促进内脏超敏反应

背景与目标

成年后，新生大鼠与母亲分离会引起内脏超敏反应并损害上皮分泌细胞谱系。母体分离引起内脏超敏反应的机制及其与上皮分泌细胞谱系缺陷的关系知之甚少。

方法

我们对从新生儿中分离出母亲的C3H / HeN小鼠和经过基因工程改造的小鼠（C57BL / 6背景上的Sox9 ^{flox / flox} -vil-cre）进行了研究，结果发现Paneth细胞缺乏。通过回肠组织的溶菌酶染色和粪便样品中的溶菌酶活性来评估Paneth细胞缺乏症。当小鼠50天大时，通过肌电图评估它们对大肠扩张的腹部反应。收集粪便样品，并使用肠道低密度阵列定量聚合酶链反应分析菌群。

结果

据大鼠报道，与没有母体分离的小鼠相比，具有母体分离的小鼠发展出内脏超敏反应和Paneth细胞缺陷。与对照同窝出生的Sox9 ^{flox / flox}小鼠相比，Sox9 ^{flox / flox} -vil-Cre小鼠的内脏超敏性也有所增加。来自具有母体分离的小鼠和来自Sox9 ^{flox / flox} -vil-cre小鼠的粪便样品具有微生物群肠道营养不良的证据，其特征在于大肠杆菌的扩增。传统的C3H / HeN成年小鼠每天用10 ^9个共生大肠埃希氏菌强饲会引起内脏超敏反应。相反，每天口服溶菌酶可阻止大肠杆菌的扩增 在产妇分离和内脏超敏反应期间。

结论

Paneth细胞中有缺陷的小鼠（由母体分离或基因工程诱导）具有大肠杆菌的肠道扩张，导致内脏超敏反应。这些发现提供了证据，表明Paneth细胞功能和肠道营养不良与内脏敏感性有关。