Aximujiang Kasimujiang, Kaheman Kuerbannaimu, Wushouer Xilinguli, Wu Guixia, Ahemaiti Abulaiti, Yunusi Kurexi
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China.
College of Pharmacy, Xinjiang Medical University, Urumqi, China.
Front Pharmacol. 2022 May 4;13:859628. doi: 10.3389/fphar.2022.859628. eCollection 2022.
Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease with complex pathogenesis. The intestinal flora disturbance affects the homeostasis of the intestinal environment, leading to metabolic imbalance and immune abnormalities of the host, contributing to the perpetuation of intestinal inflammation. We suggest that the combination of anti-inflammatory therapy and the regulation of intestinal flora balance may help in the treatment process. Previously, we used a combination treatment consisting of (Lac) and Chinese medicine Huan Kui Le (HKL) suspension in a UC rat model, where the combined intervention was more effective than either treatment alone. Herein, the mechanism of action of this combined treatment has been investigated using 16S rRNA sequencing, immunohistochemistry, and ELISA methods in the colon, and untargeted metabolomics profiling in serum. Colon protein expression levels of IL-13 and TGF-β were upregulated, whereas those of TLR9 and TLR4 were downregulated, consistent with an anti-inflammatory effect. In addition, gut microbiota structure changed, shown by a decrease in opportunistic pathogens correlated with intestinal inflammation, such as and , and an increase in beneficial bacteria such as . The latter correlated positively with IL-13 and TGF-β and negatively with IFN-γ. Finally, this treatment alleviated the disruption of the metabolic profile observed in UC rats by increasing short-chain fatty acid (SCFA)-producing bacteria in the colonic epithelium. This combination treatment also affected the metabolism of lactic acid, creatine, and glycine and inhibited the growth of . Overall, we suggest that treatment combining probiotics and traditional Chinese medicine is a novel strategy beneficial in UC that acts by modulating gut microbiota and its metabolites, TLR9, and cytokines in different pathways.
溃疡性结肠炎（UC）是一种发病机制复杂的慢性非特异性炎症性肠病。肠道菌群紊乱影响肠道环境的稳态，导致宿主代谢失衡和免疫异常，促使肠道炎症持续存在。我们认为抗炎治疗与调节肠道菌群平衡相结合可能有助于治疗过程。此前，我们在UC大鼠模型中使用了由（Lac）和中药环奎乐（HKL）悬浮液组成的联合治疗，联合干预比单独任何一种治疗都更有效。在此，我们使用16S rRNA测序、免疫组织化学和ELISA方法对结肠进行研究，并对血清进行非靶向代谢组学分析，以探究这种联合治疗的作用机制。结肠中IL-13和TGF-β的蛋白表达水平上调，而TLR9和TLR4的蛋白表达水平下调，这与抗炎作用一致。此外，肠道微生物群结构发生变化，与肠道炎症相关的机会性病原体如和减少，而有益细菌如增加。后者与IL-13和TGF-β呈正相关，与IFN-γ呈负相关。最后，这种治疗通过增加结肠上皮中产生短链脂肪酸（SCFA）的细菌，缓解了UC大鼠中观察到的代谢谱紊乱。这种联合治疗还影响了乳酸、肌酸和甘氨酸的代谢，并抑制了的生长。总体而言，我们认为益生菌与中药联合治疗是一种对UC有益的新策略，其作用机制是通过不同途径调节肠道微生物群及其代谢产物、TLR9和细胞因子。
