Sabu Kattuman Emma Elizabeth, Teegala Lakshminarayan Reddy, Darzi Somayeh, Thodeti Charles K, Paruchuri Sailaja
Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA.
Compr Physiol. 2025 Jun;15(3):e70022. doi: 10.1002/cph4.70022.
Leukotrienes are potent inflammatory lipid mediators produced primarily by immune cells. Inflammation, being the center stone of two major disease conditions, namely, asthma and inflammatory bowel disease (IBD), has led researchers to study the role of leukotrienes (LTs) in both these disease settings extensively. Several studies indicate a crucial role for LTs in the development and progression of IBD, whereas LTs, especially cysteinyl leukotrienes (cys-LTs), have been identified as the major contributors to asthma initiation and progression for over three decades. Additionally, the lungs and the gut share several common characteristics, including their exposure to the external environment, similar microbiome composition, and inflammatory responses. These similarities suggest a bidirectional relationship, supported by the increased risk of IBD in asthma patients and vice versa. However, the specific role of LTs in this lung-gut connection remains unclear. This review will examine how several common factors, such as physiology, microbiome, environment, and inflammatory mediators, especially LTs, modulate this crosstalk. The review also highlights in detail how altered leukotriene biosynthesis and signaling contribute to the pathogenesis of both asthma and IBD. Furthermore, we will consider the therapeutic implications of targeting leukotriene pathways for patients with concurrent asthma and IBD in the hope of developing more efficient treatment outcomes for these interconnected conditions. Finally, this review will very briefly explore the involvement of neuronal connections in mediating the lung-gut crosstalk.
白三烯是主要由免疫细胞产生的强效炎症性脂质介质。炎症是两种主要疾病（即哮喘和炎症性肠病（IBD））的核心，这促使研究人员广泛研究白三烯（LTs）在这两种疾病中的作用。多项研究表明白三烯在IBD的发生和发展中起关键作用，而三十多年来，白三烯，尤其是半胱氨酰白三烯（cys-LTs），已被确定为哮喘发病和进展的主要促成因素。此外，肺和肠道有几个共同特征，包括它们暴露于外部环境、相似的微生物群组成和炎症反应。这些相似性表明存在双向关系，哮喘患者患IBD的风险增加以及反之亦然的情况支持了这一点。然而，白三烯在这种肺-肠联系中的具体作用仍不清楚。本综述将探讨几个常见因素，如生理学、微生物群、环境和炎症介质，尤其是白三烯，如何调节这种相互作用。该综述还详细强调了白三烯生物合成和信号传导的改变如何导致哮喘和IBD的发病机制。此外，我们将考虑针对同时患有哮喘和IBD的患者靶向白三烯途径的治疗意义，以期为这些相互关联的疾病开发更有效的治疗结果。最后，本综述将非常简要地探讨神经连接在介导肺-肠相互作用中的作用。
