Koutromanos Ilias, Legaki Evangelia, Dovrolis Nikolas, Vassilopoulos Efthimios, Stem Arthur, Vasiliou Vasilis, Tzavellas Elias, Gazouli Maria
First Department of Psychiatry, "Aiginition" Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528, Athens, Greece.
Department of Psychiatry and Psychotherapy, Psychiatric Services Aargou AG, 5210, Brugg-Windisch, Switzerland.
Hum Genomics. 2025 Jul 11;19(1):78. doi: 10.1186/s40246-025-00793-y.
Alcohol Use Disorder (AUD) is a chronic neuropsychiatric condition with substantial public health impact. The interplay between gut microbiota and neuroplasticity-related genes presents a novel approach to understand AUD pathophysiology and treatment response. While microbial dysbiosis has been implicated in AUD, its correlation with gene expression changes in neuroplasticity pathways remains unexplored. This study investigates microbiome composition, microbial metabolic pathways, and their correlation with neuroplasticity-related genes in AUD patients undergoing treatment.
We conducted a prospective observational study integrating gut microbiome 16S rRNA sequencing and host neuroplasticity-related gene expression profiling in AUD patients undergoing treatment which combines psychotherapeutic intervention along with oral diazepam administration followed by Pythagorean Self Awareness Intervention. Patients were classified as responders or non-responders, and microbial composition, functional pathways, and host-microbiota interactions were analyzed using multi-omic correlation frameworks.
Responders exhibited a microbiome enriched in short-chain fatty acid (SCFA)-producing bacteria (e.g., Lachnospiraceae), linked to gut barrier integrity and neurotransmitter synthesis. In contrast, non-responders demonstrated enrichment of inflammation-associated taxa (Succinivibrionaceae) and oxidative stress-related metabolic pathways. Correlation analysis revealed microbiome-mediated modulation of neuroplasticity-related genes measured from peripheral blood, including BDNF, GRIA1, CAMK2G, and EGR family genes, suggesting a gut-brain-genomic axis in AUD treatment response.
This study highlights the role of gut microbiota as a modulator of neuroplasticity-related gene expression in AUD patients. Integrating microbiome and host genomic signatures could improve biomarker-based prediction of treatment response and inform precision medicine approaches for AUD. Future studies should expand these findings by incorporating multi-omic approaches, including epigenomics and exposomics, to refine microbiome-targeted interventions for addiction therapy.
酒精使用障碍（AUD）是一种对公众健康有重大影响的慢性神经精神疾病。肠道微生物群与神经可塑性相关基因之间的相互作用为理解AUD的病理生理学和治疗反应提供了一种新方法。虽然微生物失调与AUD有关，但其与神经可塑性途径中基因表达变化的相关性仍未得到探索。本研究调查了接受治疗的AUD患者的微生物组组成、微生物代谢途径及其与神经可塑性相关基因的相关性。
我们进行了一项前瞻性观察性研究，将接受治疗的AUD患者的肠道微生物组16S rRNA测序与宿主神经可塑性相关基因表达谱分析相结合，该治疗结合了心理治疗干预以及口服地西泮给药，随后进行毕达哥拉斯自我意识干预。患者被分为反应者或无反应者，并使用多组学相关框架分析微生物组成、功能途径和宿主-微生物群相互作用。
反应者表现出富含产生短链脂肪酸（SCFA）的细菌（如毛螺菌科）的微生物组，这与肠道屏障完整性和神经递质合成有关。相比之下，无反应者表现出与炎症相关的分类群（琥珀酸弧菌科）和氧化应激相关代谢途径的富集。相关性分析揭示了微生物组对外周血中测量的神经可塑性相关基因的调节作用，包括脑源性神经营养因子（BDNF）、离子型谷氨酸受体1（GRIA1）、钙/钙调蛋白依赖性蛋白激酶2γ（CAMK2G）和早期生长反应（EGR）家族基因，提示在AUD治疗反应中存在肠-脑-基因组轴。
本研究强调了肠道微生物群作为AUD患者神经可塑性相关基因表达调节因子的作用。整合微生物组和宿主基因组特征可以改善基于生物标志物的治疗反应预测，并为AUD的精准医学方法提供信息。未来的研究应通过纳入多组学方法，包括表观基因组学和暴露组学，来扩展这些发现，以完善针对成瘾治疗的微生物组靶向干预措施。
