{"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}
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.
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.