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鼠李糖乳杆菌黏膜亚种和淀粉乳杆菌通过上调结肠 5-羟色胺受体 4 和转化生长因子-β2 预防实验性结肠炎。

Limosilactobacillus mucosae and Lactobacillus amylovorus Protect Against Experimental Colitis via Upregulation of Colonic 5-Hydroxytryptamine Receptor 4 and Transforming Growth Factor-β2.

机构信息

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China.

出版信息

J Nutr. 2023 Aug;153(8):2512-2522. doi: 10.1016/j.tjnut.2023.06.031. Epub 2023 Jun 24.

DOI:10.1016/j.tjnut.2023.06.031
PMID:37356501
Abstract

BACKGROUND

Limosilactobacillusmucosae (LM) exerts anti-inflammatory and health-promoting effects. However, its role in the modulation of gut serotonin or 5-hydroxytryptamine (5-HT) metabolism and 5-HT receptors (HTRs) in inflammation requires further investigation.

OBJECTIVES

We compared LM with Lactobacillus amylovorus (LA) for the regulation of 5-HT, HTRs, inflammatory mediators, and their correlations in the colon of mice with experimental colitis.

METHODS

Male C57BL/6 mice were randomly assigned to 6 groups: control (Con), LM, LA, dextran sodium sulfate (DSS), and DSS with pre-administration of LM (+LM) or LA (+LA). After 7 d of DSS treatment, mice were killed to analyze the expression of inflammatory mediators, HTRs, and concentrations of 5-HT and microbial metabolites in the colon.

RESULTS

LM was more effective than LA in alleviating DSS-induced colonic inflammation. Compared with mice in the DSS group, mice receiving DSS + LM or DSS + LA treatment had lower (P < 0.05) colonic mRNA expression of proinflammatory cytokines. DSS + LM treatment had lower mRNA expression of Il1b, Tnfa, and Ccl3, an abundance of p-STAT3, and greater expression of Tgfb2 and Htr4 in the colon (P < 0.05). The expression of inflammatory mediators (including Tgfb-1) was positively correlated (P < 0.05) with 5-HT and Htr2a and negatively correlated (P < 0.05) with Htr4. However, the expression of Tgfb-2 showed reversed correlations with the 5-HT and HTRs described above. Patterns for these correlations were different for LM and LA. Mice receiving the DSS + LM treatment had greater (P < 0.05) concentrations of acetate and valerate and lower (P < 0.05) concentrations of indole-3-acetic acid in the cecal and colonic contents.

CONCLUSIONS

LM showed greater efficacy than LA in alleviating DSS-induced colonic inflammation. The coordinated regulation of transforming growth factor-β subtypes and serotonin receptors in the colon may be one of the most important mechanisms underlying the probiotic effects of lactobacilli in gut inflammation.

摘要

背景

黏膜罗伊氏乳杆菌(LM)具有抗炎和促进健康的作用。然而,其在调节肠道中 5-羟色胺或 5-羟色胺(5-HT)代谢和炎症中的 5-HT 受体(HTRs)方面的作用仍需进一步研究。

目的

我们比较了黏膜罗伊氏乳杆菌(LM)和嗜酸乳杆菌(LA)对实验性结肠炎小鼠结肠中 5-HT、HTRs、炎症介质及其相关性的调节作用。

方法

雄性 C57BL/6 小鼠随机分为 6 组:对照组(Con)、LM、LA、葡聚糖硫酸钠(DSS)和 DSS 预处理 LM(+LM)或 LA(+LA)。DSS 处理 7 天后,处死小鼠分析结肠中炎症介质、HTRs、5-HT 浓度和微生物代谢物的表达。

结果

与 LA 相比,LM 更能缓解 DSS 诱导的结肠炎症。与 DSS 组小鼠相比,给予 DSS+LM 或 DSS+LA 治疗的小鼠结肠中促炎细胞因子的 mRNA 表达降低(P<0.05)。DSS+LM 治疗可降低结肠中 Il1b、Tnfa 和 Ccl3 的 mRNA 表达、p-STAT3 的丰度,并增加 Tgfb2 和 Htr4 的表达(P<0.05)。炎症介质(包括 Tgfb-1)的表达与 5-HT 和 Htr2a 呈正相关(P<0.05),与 Htr4 呈负相关(P<0.05)。然而,Tgfb-2 的表达与上述 5-HT 和 HTRs 呈相反的相关性。LM 和 LA 对这些相关性的模式不同。给予 DSS+LM 治疗的小鼠盲肠和结肠内容物中乙酸和戊酸的浓度更高(P<0.05),吲哚-3-乙酸的浓度更低(P<0.05)。

结论

LM 缓解 DSS 诱导的结肠炎症的效果优于 LA。结肠中转化生长因子-β 亚型和 5-HT 受体的协调调节可能是益生菌缓解肠道炎症的重要机制之一。

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