Exploring the effects of lactulose on lung-intestinal tissue-associated factors and the TLR4/NF-κB signaling pathway in COPD rats based on lung-gut axis theory

Xinyuan Liu; Ruifeng Ding; Kun Wu; Aimin Zhang; Hongchao Fan; Jingdan Yang; Min Li

doi:10.1016/j.micpath.2024.107245

Exploring the effects of lactulose on lung-intestinal tissue-associated factors and the TLR4/NF-κB signaling pathway in COPD rats based on lung-gut axis theory

Microb Pathog. 2024 Dec 19:107245. doi: 10.1016/j.micpath.2024.107245. Online ahead of print.

Authors

Xinyuan Liu¹, Ruifeng Ding², Kun Wu², Aimin Zhang², Hongchao Fan³, Jingdan Yang¹, Min Li⁴

Affiliations

¹ Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, China.
² Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, China; Department of gastroenterology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, China.
³ Department of cardiovascular medicine, The Fourth Hospital of Baotou City, Baotou 014000, China.
⁴ Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, China; Department of gastroenterology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, China. Electronic address: 85105993@qq.com.

PMID: 39708983
DOI: 10.1016/j.micpath.2024.107245

Abstract

Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disease impacting both the respiratory and gastrointestinal systems, with its pathogenesis closely linked to the lung-gut axis theory. In this study, we established a rat model of COPD using a fumigation method combined with intra-airway administration of lipopolysaccharide (LPS) to investigate the effects of lactulose on lung and intestinal tissues, focusing on related inflammatory markers and the TLR4/NF-κB signaling pathway. We further explored the therapeutic effects and mechanisms of lactulose on the lung-intestinal tissues in COPD rats, aiming to expand its potential application in chronic respiratory diseases. Subsequently, damage to lung and colon tissue was assessed using hematoxylin and eosin (HE) staining techniques, and ultrastructural changes in lung tissue cells were observed using transmission electron microscopy. Additionally, the study detected the expression of TNF-α, IL-1β, MUC5AC, TLR4, and NF-κB in lung tissue, along with the expression of MUC2, TLR4, and NF-κB in colon tissue, to evaluate the degree of tissue damage. The research findings indicated that the integrity of the airway and colon mucosal barrier in COPD rats was compromised. Intervention with lactulose significantly reduced pathological damage to lung and intestinal tissue and improved the microstructure of lung tissue. In addition, lactulose downregulated the expression of TNF-α, IL-1β, and MUC5AC in lung tissue, upregulated the expression of MUC2 in colon tissue, and inhibited the activity of the TLR4/NF-κB signaling pathway in lung and colon tissue, effectively mitigating inflammatory damage. Our findings demonstrated that lactulose effectively alleviates COPD-associated inflammation by inhibiting the TLR4/NF-κB signaling pathway within the lung-gut axis, underscoring its promise for treating multi-organ inflammation. This study provides a novel diagnostic and therapeutic perspective for the systemic management of COPD.

Keywords: COPD; Inflammatory; Lactulose; Lung-gut axis; NF-κB; TLR4.