Hsu Chou-Yi, Mustafa Mohammed Ahmed, Moath Omar Thabit, Taher Sada Gh, Ubaid Mohammed, Gilmanova Nataliya S, Nasrat Abdulraheem Mustafa, Saadh Mohamed J, Athab Aya H, Mirzaei Rasoul, Karampoor Sajad
Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
Thunderbird School of Global Management, Arizona State University Tempe Campus, Phoenix, AZ, United States.
Front Med (Lausanne). 2024 Sep 11;11:1396789. doi: 10.3389/fmed.2024.1396789. eCollection 2024.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) marked by persistent inflammation of the mucosal lining of the large intestine, leading to debilitating symptoms and reduced quality of life. Emerging evidence suggests that an imbalance of the gut microbiota plays a crucial role in UC pathogenesis, and various signaling pathways are implicated in the dysregulated immune response. Probiotics are live microorganisms that confer health benefits to the host, have attracted significant attention for their potential to restore gut microbial balance and ameliorate inflammation in UC. Recent studies have elucidated the mechanisms by which probiotics modulate these signaling pathways, often by producing anti-inflammatory molecules and promoting regulatory immune cell function. For example, probiotics can inhibit the nuclear factor-κB (NF-κB) pathway by stabilizing Inhibitor of kappa B alpha (IκBα), dampening the production of proinflammatory cytokines. Similarly, probiotics can modulate the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, suppressing the activation of STAT1 and STAT3 and thus reducing the inflammatory response. A better understanding of the underlying mechanisms of probiotics in modulating pathogenic signaling pathways in UC will pave the way for developing more effective probiotic-based therapies. In this review, we explore the mechanistic role of probiotics in the attenuation of pathogenic signaling pathways, including NF-κB, JAK/STAT, mitogen-activated protein kinases (MAPKs), Wnt/β-catenin, the nucleotide-binding domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) inflammasome, Toll-like receptors (TLRs), interleukin-23 (IL-23)/IL-17 signaling pathway in UC.
溃疡性结肠炎（UC）是一种慢性炎症性肠病（IBD），其特征是大肠黏膜持续炎症，导致使人衰弱的症状并降低生活质量。新出现的证据表明，肠道微生物群的失衡在UC发病机制中起关键作用，并且各种信号通路与免疫反应失调有关。益生菌是对宿主有益健康的活微生物，因其恢复肠道微生物平衡和改善UC炎症的潜力而备受关注。最近的研究阐明了益生菌调节这些信号通路的机制，通常是通过产生抗炎分子和促进调节性免疫细胞功能。例如，益生菌可以通过稳定κB抑制因子α（IκBα）来抑制核因子κB（NF-κB）通路，减少促炎细胞因子的产生。同样，益生菌可以调节Janus激酶/信号转导子和转录激活子（JAK/STAT）信号通路，抑制STAT1和STAT3的激活，从而减轻炎症反应。更好地理解益生菌在调节UC致病信号通路中的潜在机制将为开发更有效的基于益生菌的疗法铺平道路。在这篇综述中，我们探讨了益生菌在减弱致病信号通路中的机制作用，这些信号通路包括NF-κB、JAK/STAT、丝裂原活化蛋白激酶（MAPK）、Wnt/β-连环蛋白、含核苷酸结合结构域（NOD）、富含亮氨酸重复序列（LRR）和吡啉结构域的蛋白3（NLRP3）炎性小体、Toll样受体（TLR）、白细胞介素-23（IL-23）/白细胞介素-17信号通路在UC中的作用。
