Gut microbiome in ALR and BPL mice (CD and HFD)

We recently reported that two mouse strains carrying a different single variation in mitochondrial complex I gene, i.e., B6-mtBPL mice carrying m.11902T>C and B6-mtALR carrying m.4738C>A exhibited differential lifespan and metabolic disease susceptibility, despite these two mouse strains showed very mild mitochondrial functional difference at the steady-state. As natural polymorphisms in the mitochondrial DNA are known to be associated with distinct patterns of gut microbial composition, we further investigated the gut microbiota composition in these mouse strains. We found that Proteobacteria, which are reportedly positively associated with pathological conditions, were significantly less abundant in B6-mtBPL mice, which showed longer lifespan and less susceptibility to high-fat diet-induced glucose intolerance, compared to B6-mtALR mice. Furthermore, functional analysis of significantly differential bacterial genera between these strains revealed that glucose metabolism pathways were significantly involved. As the whole transcriptomics analysis of hosts, i.e., the liver samples from B6-mtBPL and B6-mtALR mice, also pointed the glucose metabolism pathways were significantly differentially involved, both host gene expression and gut microbial changes caused by the mtDNA variant difference may be co-contributors to the ageing and metabolic phenotypes observed in these mouse strains. Since gut microbiota is 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.