Choline metabolism in regulating inflammatory bowel disease-linked anxiety disorders: A multi-omics exploration of the gut-brain axis
Choline metabolism in regulating inflammatory bowel disease-linked anxiety disorders: A multi-omics exploration of the gut-brain axis
复制标题
DOI：
10.1016/j.nbd.2023.106390
复制
发表时间：
2023-12
影响因子：
6.1
通讯作者：
Fan Zhang;Lingnan Guo;Jingjing Shi;Hao Jiang;Feini Zhou;Yanlin Zhou;Bin Lv;Maosheng Xu
中科院分区：
文献类型：
--
作者：
Fan Zhang;Lingnan Guo;Jingjing Shi;Hao Jiang;Feini Zhou;Yanlin Zhou;Bin Lv;Maosheng Xu
炎症性肠病（IBD）引起的焦虑和抑郁对患者的心理健康产生负面影响。新兴研究表明，肠脑轴（GBA）介导ibd诱导的情绪障碍，但这些发现的潜在机制尚不清楚。因此，对IBD的GBA进行全面研究至关重要。多组学研究可以帮助我们了解大湾区在IBD发病过程中的病理机制，有助于揭示IBD发病和进展的机制。因此，我们使用转录组学和代谢组学分析了葡聚糖硫酸钠（DSS）诱导的IBD小鼠的前额皮质（PFC）。我们观察到与对照组相比，DSS组PFC中与乙酰胆碱合成和分泌相关的mRNA增加，磷脂酰胆碱（PC）水平降低。粪便宏基因组学也显示DSS组的微生物组和脂质代谢异常。由于乙酰胆碱和PC都是胆碱代谢物，我们假设DSS组可能经历胆碱缺乏和胆碱代谢紊乱。随后，当我们补充cdp -胆碱时，IBD小鼠表现出改善，包括减少焦虑样行为，减少PC降解，增加pfc中乙酰胆碱的合成。此外，给药cdp -胆碱可以恢复肠道微生物群的失衡和DSS治疗引起的脂质代谢中断。这项研究提供了令人信服的证据，表明胆碱代谢在IBD患者情绪障碍的发展和治疗中起着至关重要的作用。胆碱及其代谢物似乎在维持大湾区的稳定中起着重要作用。
Anxiety and depression caused by inflammatory bowel disease (IBD) negatively affect the mental health of patients. Emerging studies have demonstrated that the gut-brain axis (GBA) mediates IBD-induced mood disorders, but the underlying mechanisms of these findings remain unknown. Therefore, it's vital to conduct comprehensive research on the GBA in IBD. Multi-omics studies can provide an understanding of the pathological mechanisms of the GBA in the development of IBD, helping to uncover the mechanisms underlying the onset and progression of the disease. Thus, we analyzed the prefrontal cortex (PFC) of Dextran Sulfate Sodium Salt (DSS)-induced IBD mice using transcriptomics and metabolomics. We observed increased mRNA related to acetylcholine synthesis and secretion, along with decreased phosphatidylcholine (PC) levels in the PFC of DSS group compared to the control group. Fecal metagenomics also revealed abnormalities in the microbiome and lipid metabolism in the DSS group. Since both acetylcholine and PC are choline metabolites, we posited that the DSS group may experience choline deficiency and choline metabolism disorders. Subsequently, when we supplemented CDP-choline, IBD mice exhibited improvements, including decreased anxiety-like behaviors, reduced PC degradation, and increased acetylcholine synthesis in the PFC. In addition, administration of CDP-choline can restore imbalances in the gut microbiome and disruptions in lipid metabolism caused by DSS treatment. This study provides compelling evidence to suggest that choline metabolism plays a crucial role in the development and treatment of mood disorders in IBD. Choline and its metabolites appear to have a significant role in maintaining the stability of the GBA.