Gut-Brain Axis Dysregulation in Inflammatory Bowel Disease: Implications for Coagulation Abnormalities and Extraintestinal Manifestations

Peng Lu,1,* Maolin Liu,2,* Lei Zhang,1 Jing-Jing Fan,3 Guoda Han,4 Baozhou Hou,5 Yu Meng,6 Liang Wang,7 Yan Sun1 1Department of Clinical Laboratory, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of China; 2Beijing Academy of Agriculture and Forestry Sciences, Beijing, People’s Republic of China; 3Department of Emergency ICU, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of China; 4Department of Gastrointestinal surgery, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of China; 5Department of Gastroenterology, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of China; 6Department of Hepatobiliary Pancreatic Surgery, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of China; 7Department of Endoscopic Minimally Invasive Diagnosis and Treatment, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng Lu, Department of Clinical Laboratory, Cangzhou Central Hospital, No. 16 Xinhua West Road, Yunhe District, Cangzhou, Hebei, People’s Republic of China, Email [email protected]: Inflammatory bowel disease (IBD) involves chronic intestinal inflammation driven by gut-brain axis imbalance, fostering complications through an “inflammation-neuro-coagulation” triad. Current staging systems inadequately capture the dynamics of this multidimensional network. Therefore, integrated multi-omics analyses—including metagenomics, metabolomics, and single-cell transcriptomics—are essential to construct dynamic models that monitor coagulation, microbiome, and metabolism for precise assessment of disease activity and thrombotic or bleeding risks. Interventions targeting gut-brain axis nodes, such as eliminating tissue factor-positive (TF⁺) T cells or modulating vagal activity, show potential to disrupt the inflammation-coagulation cycle, although rigorous randomized trials are still needed. Artificial intelligence (AI)-assisted systems that integrate real-time biomarker monitoring with multi-omics predictions represent a novel paradigm for managing IBD-related coagulation dysfunction. Key challenges include elucidating gut-brain-liver axis regulation of coagulation and characterizing platelet functional heterogeneity. Future efforts must prioritize ethically compliant multi-omics platforms and racially stratified risk models to advance personalized coagulation management in IBD.Plain Language Summary: 1. Inflammatory bowel disease (IBD) is closely linked to gut-brain axis imbalance, which drives intestinal and extra-intestinal complications through an “inflammation-neuro-coagulation” triad. 2. Multi-omics technologies are needed to construct dynamic monitoring models of coagulation-microbiome-metabolism for precise identification of disease activity and thrombus/bleeding risks. 3. Intervention strategies targeting key nodes of the gut-brain axis have made progress, such as eliminating tissue factor-positive (TF⁺) T cells or regulating vagus nerve activity, which shows promise in breaking the inflammation-coagulation vicious cycle. 4. Developing AI-assisted personalized anticoagulation decision systems, combined with real-time biomarker monitoring and multi-omics prediction models, provides a new paradigm for precise management of IBD complications. 5. Future research should focus on deciphering the regulatory network of the gut-brain-liver axis on coagulation balance and revealing the dynamic evolution of platelet heterogeneity in extra-intestinal thrombus formation in IBD. Keywords: inflammatory bowel disease, gut microbiota, thromboembolism, platelet dysfunction, multi-omics integration