OBJECTIVE: This study elucidates the pivotal role of LA in alleviating inflammation by regulating gut metabiota-derived metabolites and evaluating its regulative effects on promoting a balance of Th17/Treg cells in colitis mice.
METHODS: To evaluate the effect of LA on IBD,16S rRNA gene sequencing and UPLC-QTOF-MS analysis were used to identify the changes of intestinal bacteria and their metabolites. Cytokines levels were determined by ELISA and qPCR, while immune cell ratios were evaluated via flow cytometry.
RESULTS: Our findings revealed that LA treatment ameliorated general states of DSS-induced colitis mice and their accompanying depressive behaviors. Moreover, LA restricted the expression of pro-inflammatory cytokines and revised the imbalanced Treg/Th17 differentiation, while promoting SCFAs production in inflamed colon tissues. Fecal microbiota transplantation from LA-fed mice also corrected the imbalanced Treg/Th17 differentiation, indicating that LA-mediated restoration of the colonic Treg/Th17 balance mainly depends on the changes in gut metabolites.
CONCLUSIONS: These results provide scientific evidence explaining the apparent paradox of low bioavailability and high bioactivity in polyphenols, and suggesting that LA could be used as a potential dietary supplement for the prevention and improvement of IBD.
目的:本研究阐明了LA通过调节肠道多联生物代谢物缓解炎症的关键作用,并评估其对促进结肠炎小鼠Th17/Treg细胞平衡的调节作用。
方法:为了评估LA对IBD的影响,采用16SrRNA基因测序和UPLC-QTOF-MS分析鉴定肠道细菌及其代谢产物的变化。通过ELISA和qPCR测定细胞因子水平,而免疫细胞比率通过流式细胞术评估。
结果:我们的发现表明,LA治疗改善了DSS诱导的结肠炎小鼠的一般状态及其伴随的抑郁行为。此外,LA限制了促炎细胞因子的表达,改善了Treg/Th17分化的失衡,同时促进炎症结肠组织中SCFA的产生。来自LA饲喂小鼠的粪便微生物群移植也纠正了Treg/Th17分化不平衡,表明LA介导的结肠Treg/Th17平衡的恢复主要取决于肠道代谢产物的变化。
结论:这些结果提供了科学证据,解释了多酚的低生物利用度和高生物活性的明显悖论,并提示LA可用作预防和改善IBD的潜在膳食补充剂。