Recent evidence demonstrates potential links between mitochondrial dysfunction and inflammatory bowel diseases (IBD). In addition, bidirectional interactions between the intestinal microbiota and host mitochondria may modulate intestinal inflammation. We observed previously that mice deficient in the mitochondrial protein MCJ (Methylation-controlled J protein) exhibit increased susceptibility to DSS colitis. However, it is unclear whether this phenotype is primarily driven by MCJ^−/− associated gut microbiota dysbiosis or by direct effects of MCJ-deficiency. Here, we demonstrate that fecal microbiota transplantation (FMT) from MCJ-deficient into germ-free mice was sufficient to confer increased susceptibility to colitis. Therefore, an FMT experiment by cohousing was designed to alter MCJ-deficient microbiota. The phenotype resulting from complex I deficiency was reverted by FMT. In addition, we determined the protein expression pathways impacted by MCJ deficiency, providing insight into the pathophysiology of IBD. Further, we used magnetic activated cell sorting (MACS) and 16S rRNA gene sequencing to characterize taxa-specific coating of the intestinal microbiota with Immunoglobulin A (IgA-SEQ) in MCJ-deficient mice. We show that high IgA coating of fecal bacteria observed in MCJ-deficient mice play a potential role in disease progression. This study allowed us to identify potential microbial signatures in feces associated with complex I deficiency and disease progression. This research highlights the importance of finding microbial biomarkers, which might serve as predictors, permitting the stratification of ulcerative colitis (UC) patients into distinct clinical entities of the UC spectrum.

最近的证据表明线粒体功能障碍和炎症性肠病（IBD）之间存在潜在联系。此外，肠道微生物群和宿主线粒体之间的双向相互作用可能调节肠道炎症。我们之前观察到，线粒体蛋白 MCJ（甲基化控制 J 蛋白）缺陷的小鼠表现出对 DSS 结肠炎的易感性增加。然而，尚不清楚这种表型主要是由 MCJ ^−/−相关肠道微生物群失调驱动，还是由 MCJ 缺乏的直接影响驱动。在这里，我们证明将 MCJ 缺陷小鼠的粪便微生物群移植 (FMT) 到无菌小鼠体内足以增加对结肠炎的易感性。因此，设计了一项通过共养进行的 FMT 实验来改变 MCJ 缺陷的微生物群。FMT 恢复了复合物 I 缺陷导致的表型。此外，我们还确定了 MCJ 缺陷影响的蛋白质表达途径，从而深入了解 IBD 的病理生理学。此外，我们使用磁激活细胞分选 (MACS) 和 16S rRNA 基因测序来表征 MCJ 缺陷小鼠中免疫球蛋白 A (IgA-SEQ) 肠道微生物群的分类群特异性涂层。我们发现，在 MCJ 缺陷小鼠中观察到的粪便细菌的高 IgA 涂层在疾病进展中发挥着潜在作用。这项研究使我们能够识别粪便中与复合物 I 缺乏和疾病进展相关的潜在微生物特征。这项研究强调了寻找微生物生物标志物的重要性，这些生物标志物可以作为预测因子，从而将溃疡性结肠炎 (UC) 患者分层为 UC 谱系的不同临床实体。