Vatsalya Vatsalya, Verster Joris C, Sagaram Manasa, Royer Amor J, Hu Huirong, Parthasarathy Ranganathan, Schwandt Melanie L, Kong Maiying, Ramchandani Vijay A, Feng Wenke, Agrawal Ruchita, Zhang Xiang, McClain Craig J
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY, United States.
Robley Rex VA Medical Center, Louisville, KY, United States.
Front Psychiatry. 2023 Sep 29;14:1203362. doi: 10.3389/fpsyt.2023.1203362. eCollection 2023.
Patients with alcohol use disorder (AUD) exhibit symptoms such as alcohol withdrawal, depression, and cravings. The gut-immune response may play a significant role in manifesting these specific symptoms associated with AUD. This study examined the role of gut dysfunction, proinflammatory cytokines, and hormones in characterizing AUD symptoms.
Forty-eight AUD patients [men ( = 34) and women ( = 14)] aged 23-63 years were grouped using the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA) as clinically significant (CS-CIWA [score > 10] [ = 22]) and a clinically not-significant group (NCS-CIWA [score ≤ 10] [ = 26]). Clinical data (CIWA, 90-day timeline followback [TLFB90], and lifetime drinking history [LTDH]) and blood samples (for testing proinflammatory cytokines, hormones, and markers of intestinal permeability) were analyzed. A subset of 16 AUD patients was assessed upon admission for their craving tendencies related to drug-seeking behavior using the Penn-Alcohol Craving Score (PACS).
CS-CIWA group patients exhibited unique and significantly higher levels of adiponectin and interleukin (IL)-6 compared to NCS-CIWA. In the CS group, there were significant and high effects of association for the withdrawal score with gut-immune markers (lipopolysaccharide [LPS], adiponectin, IL-6, and IL-8) and for withdrawal-associated depression with gut-immune markers (scored using MADRS with LPS, soluble cells of differentiation type 14 [sCD14], IL-6, and IL-8). Craving (assessed by PACS, the Penn-Alcohol Craving Scale) was significantly characterized by what could be described as gut dysregulation (LBP [lipopolysaccharide binding protein] and leptin) and candidate proinflammatory (IL-1β and TNF-α) markers. Such a pathway model describes the heavy drinking phenotype, HDD90 (heavy drinking days past 90 days), with even higher effects (R = 0.955, = 0.006) in the AUD patients, who had higher ratings for cravings (PACS > 5).
The interaction of gut dysfunction cytokines involved in both inflammation and mediating activity constitutes a novel pathophysiological gut-brain axis for withdrawal symptoms and withdrawal-associated depression and craving symptoms in AUD. AUD patients with reported cravings show a significant characterization of the gut-brain axis response to heavy drinking.
ClinicalTrials.gov, identifier: NCT# 00106106.
酒精使用障碍（AUD）患者表现出酒精戒断、抑郁和渴望等症状。肠道免疫反应可能在表现与AUD相关的这些特定症状中起重要作用。本研究探讨了肠道功能障碍、促炎细胞因子和激素在AUD症状特征中的作用。
48例年龄在23 - 63岁的AUD患者[男性（n = 34）和女性（n = 14）]，使用酒精临床研究所戒断评估量表（CIWA）分为临床显著组（CS - CIWA [评分> 10] [n = 22]）和临床非显著组（NCS - CIWA [评分≤ 10] [n = 26]）。分析临床数据（CIWA、90天时间线追溯法[TLFB90]和终生饮酒史[LTDH]）以及血样（用于检测促炎细胞因子、激素和肠道通透性标志物）。16例AUD患者的一个子集在入院时使用宾夕法尼亚酒精渴望评分（PACS）评估其与觅药行为相关的渴望倾向。
与NCS - CIWA组相比，CS - CIWA组患者的脂联素和白细胞介素（IL）- 6水平独特且显著更高。在CS组中，戒断评分与肠道免疫标志物（脂多糖[LPS]、脂联素、IL - 6和IL - 8）以及戒断相关抑郁与肠道免疫标志物（使用蒙哥马利 - 艾森伯格抑郁评定量表[MADRS]与LPS、可溶性分化抗原簇14[sCD14]、IL - 并8评分）之间存在显著且高度的关联效应。渴望（通过PACS，即宾夕法尼亚酒精渴望量表评估）的显著特征可描述为肠道失调（脂多糖结合蛋白[LBP]和瘦素）以及候选促炎（IL - 1β和肿瘤坏死因子 - α）标志物。这样的通路模型描述了重度饮酒表型，即过去90天内的重度饮酒天数（HDD90），在对渴望评分较高（PACS > 5）的AUD患者中具有更高的效应（R = 0.955，p = 0.006）。
参与炎症和介导活性的肠道功能障碍细胞因子之间的相互作用构成了AUD中戒断症状、戒断相关抑郁和渴望症状的一种新的病理生理肠道 - 脑轴。报告有渴望的AUD患者显示出肠道 - 脑轴对重度饮酒反应的显著特征。
ClinicalTrials.gov，标识符：NCT# 00106106。
