Graduate School, Hunan University of Traditional Chinese Medicine, Changsha, China.
Department of Anorectal, the Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, China.
Front Immunol. 2024 Mar 28;15:1385907. doi: 10.3389/fimmu.2024.1385907. eCollection 2024.
The human intestinal tract constitutes a complex ecosystem, made up of countless gut microbiota, metabolites, and immune cells, with hypoxia being a fundamental environmental characteristic of this ecology. Under normal physiological conditions, a delicate balance exists among these complex "residents", with disruptions potentially leading to inflammatory bowel disease (IBD). The core pathology of IBD features a disrupted intestinal epithelial barrier, alongside evident immune and microecological disturbances. Central to these interconnected networks is hypoxia-inducible factor-1α (HIF-1α), which is a key regulator in gut cells for adapting to hypoxic conditions and maintaining gut homeostasis. Short-chain fatty acids (SCFAs), as pivotal gut metabolites, serve as vital mediators between the host and microbiota, and significantly influence intestinal ecosystem. Recent years have seen a surge in research on the roles and therapeutic potential of HIF-1α and SCFAs in IBD independently, yet reviews on HIF-1α-mediated SCFAs regulation of IBD under hypoxic conditions are scarce. This article summarizes evidence of the interplay and regulatory relationship between SCFAs and HIF-1α in IBD, pivotal for elucidating the disease's pathogenesis and offering promising therapeutic strategies.
人类肠道构成了一个复杂的生态系统，由无数肠道微生物群、代谢物和免疫细胞组成，其中缺氧是该生态系统的基本环境特征。在正常生理条件下，这些复杂的“居民”之间存在着微妙的平衡，破坏这种平衡可能导致炎症性肠病（IBD）。IBD 的核心病理学特征是肠道上皮屏障的破坏，以及明显的免疫和微生物生态紊乱。在这些相互关联的网络中，缺氧诱导因子-1α（HIF-1α）是肠道细胞适应缺氧环境和维持肠道内稳态的关键调节剂。短链脂肪酸（SCFAs）作为重要的肠道代谢物，是宿主和微生物之间的重要介质，对肠道生态系统有重要影响。近年来，人们对 HIF-1α 和 SCFAs 在 IBD 中的作用和治疗潜力进行了独立研究，但关于 HIF-1α 介导的 SCFAs 对缺氧条件下 IBD 的调节作用的综述却很少。本文总结了 IBD 中 SCFAs 和 HIF-1α 之间相互作用和调节关系的证据，这对于阐明疾病的发病机制和提供有前途的治疗策略至关重要。
