仔猪早期断奶时空肠黏膜反应的时间转录和功能动力学。

IF 3.3 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Ty M Mitchell, Heather Ann Moeser, Adam J Moeser
{"title":"仔猪早期断奶时空肠黏膜反应的时间转录和功能动力学。","authors":"Ty M Mitchell, Heather Ann Moeser, Adam J Moeser","doi":"10.1152/ajpgi.00022.2025","DOIUrl":null,"url":null,"abstract":"<p><p>Early-life adversity, including abrupt weaning, imposes significant psychosocial and environmental stress during a critical window of gastrointestinal (GI) development, leading to long-term consequences for gut function and disease susceptibility. In piglets, early weaning profoundly disrupts GI development, altering the intestinal epithelial barrier, reshaping immune function, and inducing lasting changes in the enteric nervous system. Despite these adverse outcomes, the early molecular mechanisms that initiate these alterations and set the gut on a divergent developmental trajectory remain poorly understood. Here, we utilized RNA sequencing and bioinformatic analyses to delineate early transcriptional changes in the jejunal mucosa of early-weaned male castrates compared to unweaned littermates. Ex vivo Ussing chamber experiments validated functional changes associated with these transcriptional alterations. Weaning triggered rapid transcriptional shifts observable within 3 hours, including suppressed mitochondrial energy production and increased glucose transporter expression. Pathway analysis revealed upregulation of ion channel transport genes (KCN, SCN, TRP, SLC) and neurotransmitter receptors (cholinergic, dopaminergic, GABAergic, glutamatergic), indicating early neuronal adaptations. Functional assays confirmed enhanced SGLT-mediated glucose transport and neural-evoked secretory responses 24 hours post-weaning, supporting transcriptomic findings. These findings reveal previously unexamined early transcriptional and functional changes that may serve as inciting mechanisms altering gut trajectory during this critical developmental window, providing new insight into how psychosocial stress and early weaning contribute to long-term gut dysfunction, with broader implications for preterm birth, neonatal GI injury, and other early-life stressors that impact lifelong GI health.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Temporal Transcriptional and Functional Dynamics of Jejunal Mucosal Response to Early Weaning in Piglets.\",\"authors\":\"Ty M Mitchell, Heather Ann Moeser, Adam J Moeser\",\"doi\":\"10.1152/ajpgi.00022.2025\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Early-life adversity, including abrupt weaning, imposes significant psychosocial and environmental stress during a critical window of gastrointestinal (GI) development, leading to long-term consequences for gut function and disease susceptibility. In piglets, early weaning profoundly disrupts GI development, altering the intestinal epithelial barrier, reshaping immune function, and inducing lasting changes in the enteric nervous system. Despite these adverse outcomes, the early molecular mechanisms that initiate these alterations and set the gut on a divergent developmental trajectory remain poorly understood. Here, we utilized RNA sequencing and bioinformatic analyses to delineate early transcriptional changes in the jejunal mucosa of early-weaned male castrates compared to unweaned littermates. Ex vivo Ussing chamber experiments validated functional changes associated with these transcriptional alterations. Weaning triggered rapid transcriptional shifts observable within 3 hours, including suppressed mitochondrial energy production and increased glucose transporter expression. Pathway analysis revealed upregulation of ion channel transport genes (KCN, SCN, TRP, SLC) and neurotransmitter receptors (cholinergic, dopaminergic, GABAergic, glutamatergic), indicating early neuronal adaptations. Functional assays confirmed enhanced SGLT-mediated glucose transport and neural-evoked secretory responses 24 hours post-weaning, supporting transcriptomic findings. These findings reveal previously unexamined early transcriptional and functional changes that may serve as inciting mechanisms altering gut trajectory during this critical developmental window, providing new insight into how psychosocial stress and early weaning contribute to long-term gut dysfunction, with broader implications for preterm birth, neonatal GI injury, and other early-life stressors that impact lifelong GI health.</p>\",\"PeriodicalId\":7725,\"journal\":{\"name\":\"American journal of physiology. Gastrointestinal and liver physiology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-09-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of physiology. Gastrointestinal and liver physiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1152/ajpgi.00022.2025\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of physiology. Gastrointestinal and liver physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1152/ajpgi.00022.2025","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

生命早期的逆境,包括突然断奶,在胃肠道(GI)发育的关键窗口期施加了重大的社会心理和环境压力,导致肠道功能和疾病易感性的长期后果。在仔猪中,早期断奶严重破坏胃肠道发育,改变肠上皮屏障,重塑免疫功能,并诱导肠神经系统的持久变化。尽管有这些不良后果,但启动这些改变并使肠道处于不同发育轨迹的早期分子机制仍然知之甚少。在这里,我们利用RNA测序和生物信息学分析来描绘早期断奶的雄性阉割鼠空肠黏膜的早期转录变化与未断奶的窝鼠相比。体外实验验证了与这些转录改变相关的功能变化。断奶会在3小时内触发可观察到的快速转录变化,包括抑制线粒体能量产生和增加葡萄糖转运蛋白表达。通路分析显示,离子通道转运基因(KCN、SCN、TRP、SLC)和神经递质受体(胆碱能、多巴胺能、gaba能、谷氨酸能)上调,表明早期神经元适应。功能分析证实,断奶后24小时sglt介导的葡萄糖转运和神经诱发的分泌反应增强,支持转录组学研究结果。这些发现揭示了以前未被研究过的早期转录和功能变化,这些变化可能是在这一关键发育窗口期改变肠道轨迹的刺激机制,为社会心理压力和早期断奶如何导致长期肠道功能障碍提供了新的见解,对早产、新生儿胃肠道损伤和其他影响终生胃肠道健康的早期生活压力源具有更广泛的意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Temporal Transcriptional and Functional Dynamics of Jejunal Mucosal Response to Early Weaning in Piglets.

Early-life adversity, including abrupt weaning, imposes significant psychosocial and environmental stress during a critical window of gastrointestinal (GI) development, leading to long-term consequences for gut function and disease susceptibility. In piglets, early weaning profoundly disrupts GI development, altering the intestinal epithelial barrier, reshaping immune function, and inducing lasting changes in the enteric nervous system. Despite these adverse outcomes, the early molecular mechanisms that initiate these alterations and set the gut on a divergent developmental trajectory remain poorly understood. Here, we utilized RNA sequencing and bioinformatic analyses to delineate early transcriptional changes in the jejunal mucosa of early-weaned male castrates compared to unweaned littermates. Ex vivo Ussing chamber experiments validated functional changes associated with these transcriptional alterations. Weaning triggered rapid transcriptional shifts observable within 3 hours, including suppressed mitochondrial energy production and increased glucose transporter expression. Pathway analysis revealed upregulation of ion channel transport genes (KCN, SCN, TRP, SLC) and neurotransmitter receptors (cholinergic, dopaminergic, GABAergic, glutamatergic), indicating early neuronal adaptations. Functional assays confirmed enhanced SGLT-mediated glucose transport and neural-evoked secretory responses 24 hours post-weaning, supporting transcriptomic findings. These findings reveal previously unexamined early transcriptional and functional changes that may serve as inciting mechanisms altering gut trajectory during this critical developmental window, providing new insight into how psychosocial stress and early weaning contribute to long-term gut dysfunction, with broader implications for preterm birth, neonatal GI injury, and other early-life stressors that impact lifelong GI health.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
9.40
自引率
2.20%
发文量
104
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Gastrointestinal and Liver Physiology publishes original articles pertaining to all aspects of research involving normal or abnormal function of the gastrointestinal tract, hepatobiliary system, and pancreas. Authors are encouraged to submit manuscripts dealing with growth and development, digestion, secretion, absorption, metabolism, and motility relative to these organs, as well as research reports dealing with immune and inflammatory processes and with neural, endocrine, and circulatory control mechanisms that affect these organs.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信