Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Department of Gastroenterology, Third Military Medical University Second Affiliated Hospital, Chongqing, 400037, China.
Pharmacol Res. 2022 Jan;175:105992. doi: 10.1016/j.phrs.2021.105992. Epub 2021 Nov 18.
Recent evidence suggests that neuropsychiatric stabilizers have a place in resolving gastrointestinal disorders. Lithium carbonate (LC) is one of the most commonly used drugs for bipolar disorder clinically. Here, we estimate the therapeutic function of LC against colitis and investigate the mechanism of intestinal flora and metabolism modulation.
A colitis model was constructed by continuously administering 2.5% dextran sodium sulfate (DSS) solution daily for 7 days. Analysis of gut microbiota was carried out by 16S rRNA gene high-throughput sequencing. Spectrum antibiotic cocktail (ABX) and faecal microbiota transplantation (FMT) were employed to evaluate the protective effect of intestinal flora. Colonic Treg cells and related immune responses were detected by flow cytometry.
LC treatment significantly alleviated colon inflammation by regulating gut microbial diversity and altering flora composition. Notably, LC treatment upregulated short-chain fatty acid (SCFA)-producing bacteria, especially Akkermansia muciniphila (A. muciniphila), and transformed metabolite SCFA profiles. LC activated anti-inflammatory Treg cell responses in colonic lamina propria (LP) in a G-protein coupled receptor 43 (GPR43)-dependent mechanism. ABX, FMT and single bacteria gavage experiments were conducted to confirm the above mechanism.
As an intestinal microbiome and metabolite modulator, LC alleviates colon inflammation in a GPR43-dependent manner through activating Treg cell responses. Therefore, the therapeutic strategy of the microbiome-metabolite-immune axis, as observed in the A. muciniphila-SCFA-Treg cell axis in our study, might provide a new direction for the treatment of IBD.
最近的证据表明，神经精神稳定剂在解决胃肠道疾病方面有一定作用。碳酸锂（LC）是临床治疗双相情感障碍最常用的药物之一。在这里，我们评估了 LC 对结肠炎的治疗作用，并研究了肠道菌群和代谢调节的机制。
通过连续 7 天每天给予 2.5%葡聚糖硫酸钠（DSS）溶液构建结肠炎模型。通过 16S rRNA 基因高通量测序进行肠道微生物组分析。采用广谱抗生素鸡尾酒（ABX）和粪便微生物群移植（FMT）来评估肠道菌群的保护作用。通过流式细胞术检测结肠 Treg 细胞和相关免疫反应。
LC 治疗通过调节肠道微生物多样性和改变菌群组成显著缓解结肠炎症。值得注意的是，LC 治疗上调了短链脂肪酸（SCFA）产生菌，特别是阿克曼氏菌（A. muciniphila），并改变了代谢物 SCFA 谱。LC 通过 G 蛋白偶联受体 43（GPR43）依赖性机制激活结肠固有层（LP）中的抗炎性 Treg 细胞反应。进行了 ABX、FMT 和单细菌灌胃实验以证实上述机制。
作为肠道微生物组和代谢物调节剂，LC 通过激活 Treg 细胞反应，以 GPR43 依赖的方式缓解结肠炎症。因此，我们研究中观察到的微生物组-代谢物-免疫轴的治疗策略，可能为治疗 IBD 提供新的方向。
