Lübeck Institute of Experimental Dermatology, University of Lübeck, 23562 Lübeck, Germany.
Institute for Cardiogenetics, University of Lübeck, 23562 Lübeck, Germany.
Int J Mol Sci. 2022 Jan 19;23(3):1056. doi: 10.3390/ijms23031056.
We recently reported on two mouse strains carrying different single nucleotide variations in the mitochondrial complex I gene, i.e., B6-mt mice carrying m.11902T>C and B6-mt carrying m.4738C>A. B6-mt mice exhibited a longer lifespan and a lower metabolic disease susceptibility despite mild mitochondrial functional differences in steady-state. As natural polymorphisms in the mitochondrial DNA (mtDNA) are known to be associated with distinct patterns of gut microbial composition, we further investigated the gut microbiota composition in these mice strains. In line with mouse phenotypes, we found a significantly lower abundance of , which is positively associated with pathological conditions, in B6-mt compared to B6-mt mice. A prediction of functional profile of significantly differential bacterial genera between these strains revealed an involvement of glucose metabolism pathways. Whole transcriptome analysis of liver samples from B6-mt and B6-mt mice confirmed these findings. Thus, both host gene expression and gut microbial changes caused by the mtDNA variant differences may contribute to the ageing and metabolic phenotypes observed in these mice strains. Since gut microbiota are easier to modulate, compared with mtDNA variants, identification of such mtDNA variants, specific gut bacterial species and bacterial metabolites may be a potential intervention to modulate common diseases, which are differentially susceptible to individuals with different mtDNA variants.
我们最近报道了两种携带线粒体复合物 I 基因不同单核苷酸变异的小鼠品系，即携带 m.11902T>C 的 B6-mt 小鼠和携带 m.4738C>A 的 B6-mt 小鼠。尽管在稳定状态下线粒体功能存在轻微差异，但 B6-mt 小鼠表现出更长的寿命和更低的代谢疾病易感性。由于线粒体 DNA（mtDNA）中的天然多态性与肠道微生物组成的不同模式有关，我们进一步研究了这些小鼠品系的肠道微生物群落组成。与小鼠表型一致，我们发现 B6-mt 小鼠中与病理状况呈正相关的丰度显著降低，与 B6-mt 小鼠相比，丰度显著降低。对这些菌株之间差异显著的细菌属的功能谱进行预测，发现葡萄糖代谢途径的参与。B6-mt 和 B6-mt 小鼠肝脏样本的全转录组分析证实了这些发现。因此，由 mtDNA 变异引起的宿主基因表达和肠道微生物变化可能导致这些小鼠品系观察到的衰老和代谢表型。由于与 mtDNA 变异相比，肠道微生物更容易调节，因此鉴定这种 mtDNA 变异、特定肠道细菌种类和细菌代谢物可能是调节个体易感性不同的常见疾病的潜在干预措施。
