Cadwell Ken, Loke P'ng
Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA.
Nat Immunol. 2025 Jun 17. doi: 10.1038/s41590-025-02197-5.
Inflammatory bowel disease (IBD) is a complex, multifactorial inflammatory disorder of the gut characterized by an imbalance in host-microbiota interactions. Here, we review how early events of IBD are shaped by gene-environment interactions, especially those involving microbial perturbations. Those perturbations eventually lead to chronic inflammation and tissue damage of the gastrointestinal tract. IBD is a multi-hit process in which infectious and noninfectious agents initiate a cascade of immune activation in genetically susceptible individuals. Ultimately the process results in irreversible immunological and physical scarring. These interactions are host specific, with genetic variants influencing the threshold for immune activation and the degree of damage, thus leading to variability in disease progression and therapeutic outcomes. Finally, we discuss challenges, including addressing health disparities and potential strategies for more personalized and effective therapies that target host-microbiota interactions during the preclinical phase of IBD.
炎症性肠病（IBD）是一种复杂的、多因素的肠道炎症性疾病，其特征是宿主与微生物群相互作用失衡。在此，我们综述炎症性肠病的早期事件如何由基因-环境相互作用塑造，尤其是那些涉及微生物扰动的相互作用。这些扰动最终导致胃肠道的慢性炎症和组织损伤。炎症性肠病是一个多步骤过程，其中感染性和非感染性因素在基因易感个体中引发一系列免疫激活。最终，该过程导致不可逆的免疫和物理瘢痕形成。这些相互作用具有宿主特异性，基因变异影响免疫激活阈值和损伤程度，从而导致疾病进展和治疗结果的变异性。最后，我们讨论了挑战，包括解决健康差异以及在炎症性肠病临床前阶段针对宿主-微生物群相互作用的更个性化和有效治疗的潜在策略。
