REVIEW article
Front. Immunol.
Sec. Inflammation
This article is part of the Research TopicMetabolic Implications in Sepsis and Inflammation-related Critical IllnessesView all 12 articles
Mechanisms and Therapeutic of Immunometabolic Reprogramming Driving Macrophage-Endothelial Cell Interactions in Sepsis-Associated ARDS from the Gut-Lung Axis Perspective
Provisionally accepted
- Army Medical Center of PLA, Chongqing, China
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Acute respiratory distress (ARDS) caused by sepsis is a critical inflammatory condition with high mortality rates in clinical settings. The gut-lung axis plays a crucial role in regulating the immune response in both the intestinal and pulmonary environments, significantly impacting the development of ARDS. Immunometabolic reprogramming, a fundamental regulator of immune cell function, has recently been shown to profoundly affect the activity of macrophages and endothelial cells (ECs), as well as their crosstalk, thereby shaping the pathogenesis of ARDS. While a great deal has been learned about the potential inflammatory pathways involved, few clinically actionable therapies are available in part due to an incomplete understanding of gut-lung crosstalk in their shared ecosystem of cells and molecules. The current review systematically advances novel insights into the immunometabolic reprogramming that influences macrophage-endothelial cell interactions via sepsis-induced ARDS, with a specific regard to the gut-lung axis. Here, we summarize the key biochemical pathways that control immune cell phenotypes and endothelial function, review the latest experimental evidence for their intercellular crosstalk, and describe the molecular targets that might be targeted to inform therapeutic strategies. Integrating the current evidence, this review seeks to provide a comprehensive theoretical framework and novel methods for the precise treatment of sepsis-associated ARDS, which could be beneficial to clinical practices and patients' prognoses.
Keywords: Sepsis, ARDS, Gut-Lung Axis, immunometabolic reprogramming, Macrophages, ECS, Cell interaction, Inflammatory Response
Received: 23 Oct 2025; Accepted: 16 Jan 2026.
Copyright: © 2026 Tang, Yan, Li, Li and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jia Tang
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