Novel hypothesis and therapeutic interventions for irritable bowel syndrome: interplay between metal dyshomeostasis, gastrointestinal dysfunction, and neuropsychiatric symptoms.

IF 3.5 2区 生物学 Q3 CELL BIOLOGY
Yutaka Nakagawa, Shizuo Yamada
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引用次数: 0

Abstract

Irritable bowel syndrome is a gastrointestinal disorder due to multiple pathologies. While patients with this condition experience anxiety and depressed mood more frequently than healthy individuals, it is unclear how gastrointestinal dysfunction interacts with such neuropsychiatric symptoms. Data suggest that irritable bowel syndrome patients predominantly display a lower zinc intake, which presumably impairs enterochromaffin cells producing 5-hydroxytryptamine, gut bacteria fermenting short-chain fatty acids, and barrier system in the intestine, with the accompanying constipation, diarrhea, low-grade mucosal inflammation, and visceral pain. Dyshomeostasis of copper and zinc concentrations as well as elevated pro-inflammatory cytokine levels in the blood can disrupt blood-cerebrospinal fluid barrier function, leading to locus coeruleus neuroinflammation and hyperactivation with resultant amygdalar overactivation and dorsolateral prefrontal cortex hypoactivation as found in neuropsychiatric disorders. The dysregulation between the dorsolateral prefrontal cortex and amygdala is likely responsible for visceral pain-related anxiety, depressed mood caused by anticipatory anxiety, and visceral pain catastrophizing due to catastrophic thinking or cognitive distortion. Collectively, these events can result in a spiral of gastrointestinal symptoms and neuropsychiatric signs, prompting the progression of irritable bowel syndrome. Given that the negative feedback mechanism in regulation of the hypothalamic-pituitary-adrenal axis is preserved in a subset of neuropsychiatric cases, dorsolateral prefrontal cortex abnormality accompanied by neuropsychiatric symptoms may be a more significant contributing factor in brain-gut axis malfunction than activation of the hypothalamic corticotropin-releasing hormone system. The proposed mechanistic model could predict novel therapeutic interventions for comorbid irritable bowel syndrome and neuropsychiatric disorders.

肠易激综合征的新假设和治疗干预:金属失衡、胃肠功能紊乱和神经精神症状之间的相互作用。
肠易激综合征是一种由多种病理因素引起的胃肠道疾病。与健康人相比,肠易激综合征患者更经常出现焦虑和情绪低落,但目前还不清楚胃肠道功能障碍与这些神经精神症状之间是如何相互作用的。数据显示,肠易激综合征患者主要表现为锌摄入量较低,这可能会损害产生 5-羟色胺的肠粘膜细胞、发酵短链脂肪酸的肠道细菌和肠道屏障系统,并伴随便秘、腹泻、低度粘膜炎症和内脏疼痛。铜和锌浓度失衡以及血液中促炎细胞因子水平的升高会破坏血-脑脊液屏障功能,导致神经炎症和神经过度激活,从而导致杏仁核过度激活和背外侧前额叶皮层激活不足,这在神经精神疾病中也会发现。背外侧前额叶皮层和杏仁核之间的失调很可能是内脏疼痛相关焦虑、预期性焦虑导致的情绪低落以及灾难性思维或认知扭曲导致的内脏疼痛灾难化的原因。总之,这些事件会导致胃肠道症状和神经精神症状的螺旋式上升,促使肠易激综合征的发展。鉴于调节下丘脑-垂体-肾上腺轴的负反馈机制在一部分神经精神疾病病例中得以保留,与激活下丘脑促肾上腺皮质激素释放激素系统相比,伴有神经精神症状的前额叶皮质背外侧异常可能是导致脑-肠轴功能失调的更重要因素。所提出的机理模型可预测对合并肠易激综合征和神经精神障碍的新型治疗干预措施。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry 生物-细胞生物学
CiteScore
8.30
自引率
2.30%
发文量
293
审稿时长
1.7 months
期刊介绍: Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
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