Morena Donato, Lippi Matteo, Scopetti Matteo, Turillazzi Emanuela, Fineschi Vittorio
Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, 00161 Rome, Italy.
Department of Medical Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy.
Diagnostics (Basel). 2025 Jul 1;15(13):1683. doi: 10.3390/diagnostics15131683.
: The gut-brain axis (GBA) has been demonstrated to be involved in normal neurodevelopment, with its dysfunction potentially contributing to the onset of mental disorders. In this systematic review and meta-analysis, we aimed to examine the relationship between levels of specific biomarkers of intestinal permeability or inflammation and scores of depressive symptoms or suicidality. : All studies investigating the link between depressive symptoms and/or suicidality and biomarkers associated with intestinal permeability or inflammation were included. Studies providing data for comparisons between two groups-depressive or suicidal patients vs. healthy controls, or suicidal vs. non-suicidal patients-were included in the meta-analysis. Studies examining the correlation between depressive symptoms and biomarker levels were also included into the review. Data were independently extracted and reviewed by multiple observers. A random-effects model was employed for the analysis, and Hedge's g was pooled for the effect size. Heterogeneity was assessed using the I index. : Twenty-two studies provided data for inclusion in the meta-analysis, while nineteen studies investigated the correlation between depressive symptoms and biomarker levels. For depressive symptoms, when compared to the controls, patients showed significantly increased levels of intestinal fatty acid-binding protein (I-FABP) (ES = 0.36; 95% CI = 0.11 to 0.61; = 0.004; I = 71.61%), zonulin (ES = 0.69; 95% CI = 0.02 to 1.36; = 0.044; I = 92.12%), antibodies against bacterial endotoxins (ES = 0.75; 95% CI = 0.54 to 0.98; < 0.001; I = 0.00%), and sCD14 (ES = 0.11; 95% CI = 0.01 to 0.21; = 0.038; I = 10.28%). No significant differences were found between the patients and controls in levels of LPS-binding protein (LBP) and alpha-1 antitrypsin (A-1-AT). For suicidality, four studies were identified for quantitative analysis, three of which focused on I-FABP. No significant differences in I-FABP levels were observed between suicidal patients and the controls (ES = 0.24; 95% CI = -0.30 to 0.79; = 0.378; I = 86.44%). Studies investigating the correlation between depressive symptoms and levels of intestinal permeability and inflammation biomarkers did not provide conclusive results. : A significant difference was observed between patients with depressive symptoms and controls for biomarkers of intestinal permeability (zonulin, which regulates tight junctions), inflammatory response to bacterial endotoxins (antibodies to endotoxins and sCD14-a soluble form of the CD14 protein that modulates inflammation triggered by lipopolysaccharides), and acute intestinal epithelial damage (I-FABP, released upon enterocyte injury). Studies investigating suicidality and related biomarkers were limited in number and scope, preventing definitive conclusions. Overall, these findings suggest that biomarkers of gut permeability represent a promising area for further investigation in both psychiatric and forensic pathology. They may have practical applications, such as supporting diagnostic and therapeutic decision-making in clinical settings and providing pathologists with additional information to help determine the manner of death in forensic investigations.
肠-脑轴(GBA)已被证明参与正常的神经发育,其功能障碍可能导致精神障碍的发生。在这项系统评价和荟萃分析中,我们旨在研究肠道通透性或炎症的特定生物标志物水平与抑郁症状或自杀倾向评分之间的关系。
纳入所有调查抑郁症状和/或自杀倾向与肠道通透性或炎症相关生物标志物之间联系的研究。提供两组(抑郁或自杀患者与健康对照,或自杀与非自杀患者)比较数据的研究纳入荟萃分析。审查还纳入了研究抑郁症状与生物标志物水平之间相关性的研究。数据由多名观察者独立提取和审查。采用随机效应模型进行分析,并汇总Hedge's g作为效应量。使用I指数评估异质性。
22项研究提供了纳入荟萃分析的数据,19项研究调查了抑郁症状与生物标志物水平之间的相关性。对于抑郁症状,与对照组相比,患者的肠道脂肪酸结合蛋白(I-FABP)水平显著升高(效应量=0.36;95%置信区间=0.11至0.61;P=0.004;I²=71.61%)、闭合蛋白(效应量=0.69;95%置信区间=0.02至1.36;P=0.044;I²=92.12%)、抗细菌内毒素抗体(效应量=0.75;95%置信区间=0.54至0.98;P<0.001;I²=0.00%)和可溶性CD抗原14(sCD14)(效应量=0.11;95%置信区间=0.01至0.21;P=0.038;I²=10.28%)。患者与对照组的脂多糖结合蛋白(LBP)和α-1抗胰蛋白酶(A-1-AT)水平无显著差异。对于自杀倾向,确定了4项研究进行定量分析,其中3项关注I-FABP。自杀患者与对照组的I-FABP水平无显著差异(效应量=0.24;95%置信区间=-0.30至0.79;P=0.378;I²=86.44%)。研究抑郁症状与肠道通透性和炎症生物标志物水平之间相关性的研究未提供确凿结果。
抑郁症状患者与对照组在肠道通透性生物标志物(调节紧密连接的闭合蛋白)、对细菌内毒素炎症反应(内毒素抗体和sCD14,一种调节脂多糖引发炎症的CD14蛋白可溶性形式)和急性肠上皮损伤(I-FABP,在肠上皮细胞损伤时释放)方面存在显著差异。研究自杀倾向及相关生物标志物的研究数量和范围有限,无法得出明确结论。总体而言,这些发现表明肠道通透性生物标志物是精神病学和法医病理学中一个有前景的进一步研究领域。它们可能具有实际应用,例如在临床环境中支持诊断和治疗决策,并为病理学家提供额外信息,以帮助在法医调查中确定死亡方式。
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