The clinical spectra of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) intersect to form a scantily defined overlap syndrome, termed pre-IBD. We show that increased Enterobacteriaceae and reduced Clostridia abundance distinguish the fecal microbiota of pre-IBD patients from IBS patients. A history of antibiotics in individuals consuming a high-fat diet was associated with the greatest risk for pre-IBD. Exposing mice to these risk factors resulted in conditions resembling pre-IBD and impaired mitochondrial bioenergetics in the colonic epithelium, which triggered dysbiosis. Restoring mitochondrial bioenergetics in the colonic epithelium with 5-amino salicylic acid, a PPAR-γ (peroxisome proliferator–activated receptor gamma) agonist that stimulates mitochondrial activity, ameliorated pre-IBD symptoms. As with patients, mice with pre-IBD exhibited notable expansions of Enterobacteriaceae that exacerbated low-grade mucosal inflammation, suggesting that remediating dysbiosis can alleviate inflammation. Thus, environmental risk factors cooperate to impair epithelial mitochondrial bioenergetics, thereby triggering microbiota disruptions that exacerbate inflammation and distinguish pre-IBD from IBS.

肠易激综合征 (IBS) 和炎症性肠病 (IBD) 的临床谱交叉形成一种定义不明确的重叠综合征，称为前 IBD。我们表明肠杆菌科细菌增加和梭状芽孢杆菌减少丰度区分 IBD 前患者和 IBS 患者的粪便微生物群。食用高脂肪饮食的个体使用抗生素史与 IBD 前兆的最大风险相关。将小鼠暴露于这些风险因素会导致类似于前 IBD 的状况和结肠上皮中线粒体生物能学受损，从而引发生态失调。用 5-氨基水杨酸（一种刺激线粒体活性的 PPAR-γ（过氧化物酶体增殖物激活受体 γ）激动剂）恢复结肠上皮中的线粒体生物能，改善了 IBD 前症状。与患者一样，患有前 IBD 的小鼠表现出肠杆菌科的显着扩张这加剧了低度黏膜炎症，表明修复生态失调可以缓解炎症。因此，环境风险因素共同损害上皮线粒体生物能量学，从而引发微生物群破坏，从而加剧炎症并区分 IBD 前期和 IBS。