Alzheimer’s disease (AD) research is shifting from a “brain-centered” model toward a “gut-brain axis system” perspective. However, the causal roles of gut microbiota in AD pathology remain elusive, as traditional association studies struggle to distinguish potential drivers from passengers. This review examines the potential applications and inherent limitations of artificial intelligence (AI) in dissecting this complex relationship. We discuss three emerging and conceptually promising directions: First, AI-frameworks for hypothesis-generating causal discovery that can prioritize microbiota-AD relationships for subsequent experimental validation, while recognizing that current approaches predominantly identify statistical associations rather than empirically supported causal conclusions; second, multi-modal fusion networks, when applied with appropriate regularization and validation, can assist in constructing cross-scale molecular maps across microbiota, metabolites, and the brain, though such pathway inferences require careful interpretation as they represent statistical associations rather than biochemically validated mechanisms; and third, the conceptual application of digital twin-based simulation as a long-term vision for personalized microbiota modulation, which currently lacks the ecological resolution and validation required for predictive modeling. By integrating multi-pathway mechanisms of the gut-brain axis and characteristic profiles of gut microbiota, we critically evaluate the technical advantages of machine learning in microbiome data analysis alongside major challenges including overfitting, batch effects, confounding factors, and reproducibility. Leveraging AI-driven microbiota analysis, we propose a phased translational roadmap, from near-term standardization and cross-cohort validation, through mid-term endophenotyping and trial enrichment strategies, to the long-term exploration of personalized interventions, toward the eventual goal of precision prevention. This article outlines a full-cycle framework from discovery to clinical translation and envisions a conceptual ecosystem for future intelligent microecological health management. Achieving the promise of AI-empowered gut-brain axis research will require deep integration across neuroscience, microbiology, computational science, and clinical medicine, alongside rigorous experimental validation, standardized protocols, and realistic appraisal of current technological boundaries.
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Chemokine-like factor 1 (CKLF1) is a chemokine that is overexpressed in several diseases. Our previous findings revealed a significant increase in CKLF1 expression in the ischemic brain, suggesting its potential as a therapeutic target for ischemic stroke.
In this study, we examined the expression dynamics of CKLF1 in both in vivo and in vitro models of ischemic cardiac injury. Myocardial infarction (MI) was induced in vivo by ligation of the left anterior descending artery (LAD) of the rat heart. The levels of CKLF1, Creatine Kinase MB Isoenzyme (CK-MB), and Lactate dehydrogenase (LDH) in the serum were detected using Enzyme-linked immunosorbent assay (ELISA). The expression of CKLF1 in the infarcted area was detected by immunohistochemistry, immunofluorescence, quantitative PCR (qPCR), and Western blotting (WB). H9C2 and AC16 cardiomyocytes cultured in vitro were subjected to oxygen and glucose deprivation (OGD). LDH was used to detect cell damage, and CKLF1 expression was detected by qPCR and WB.
CKLF1 mRNA and protein expression were significantly increased in h9c2 cells at 1.5 h and in AC16 cells at 4 h after OGD. The serum CK-MB in rats increased significantly on the first day after infarction, while the LDH concentration increased significantly on the third day after infarction. CKLF1 blood levels significantly increased on the first day following MI in rats. CKLF1 expression notably increased in the infarct area on days 1, 3, and 7 post-MI. In MI tissue, CKLF1 colocalizes with cardiomyocytes, macrophages, and neutrophils.
CKLF1 was substantially expressed during myocardial ischemia injury both in vivo and in vitro and was colocalized with macrophages and neutrophils, indicating that CKLF1 is expected to be a biomarker and a drug target for the treatment of myocardial infarction.
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