Homeostasis of the gut barrier and potential biomarkers.
Homeostasis of the gut barrier and potential biomarkers.
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DOI：
10.1152/ajpgi.00048.2015
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发表时间：
2017-03-01
期刊：
影响因子：
--
通讯作者：
Garcia-Rodenas CL
中科院分区：
文献类型：
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作者：
Wells JM;Brummer RJ;Derrien M;MacDonald TT;Troost F;Cani PD;Theodorou V;Dekker J;Méheust A;de Vos WM;Mercenier A;Nauta A;Garcia-Rodenas CL
肠道屏障通过分泌粘液的产生将细菌空间区室化到管腔中起着至关重要的作用，并且通过分泌型伊加（sIgA）和抗微生物肽和蛋白质的产生来加强。除sIgA外，这些保护性屏障因子的表达主要受微生物分子配体的先天免疫识别控制。几个专门的适应和检查点在粘膜中运作，以根据威胁来调整免疫反应，并防止对居住在人类肠道中的数万亿共生体的过度反应。健康的微生物群通过产生短链脂肪酸（SCFA）和与粘膜中的先天模式识别受体相互作用，驱动粘液和抗微生物因子的稳态表达，对影响上皮屏障功能起着关键作用。然而，肠道屏障稳态的扰动可导致炎性信号传导增加、上皮通透性增加和微生物群的生态失调，其被认为在多种胃肠道病症的病理生理学中起作用。此外，肠-脑信号传导可能受到长期粘膜免疫激活的影响，导致传入感觉信号传导增加和腹部症状。反过来，神经元机制可以部分地通过激活下丘脑-垂体-肾上腺轴以及肥大细胞依赖性和肥大细胞非依赖性机制来影响肠屏障。通过营养干预调节肠道屏障功能，包括操纵微生物群的策略，被认为是针对一系列疾病的新型治疗和预防性治疗的相关目标。几种生物标志物已被用于测量肠道疾病的肠道通透性和屏障完整性的损失，但仍然需要探索它们在评估营养因素对肠道屏障功能的影响中的用途。未来的研究应旨在建立可用生物标志物的正常范围及其对人类队列肠道健康的预测价值。
The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell-dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of available biomarkers and their predictive value for gut health in human cohorts.