Gut microbiota alterations in individuals with mitochondrial disease caused by the m.3243A >G mutation.

People with mitochondrial disease (MD) associated with the m.3243 A > G mutation often experience gastrointestinal complaints and dysmotility, suggesting dysbiosis of the gut microbiome. A common phenotype of the m.3243 A > G mutation is Maternally Inherited Diabetes and Deafness (MIDD). Previous studies have shown that other forms of diabetes are associated with an altered gut microbiome. Therefore, our study aimed to investigate the gut microbiota of people with MD caused by the m.3243 A > G mutation compared to healthy controls (Lifelines®) and people with type 1 diabetes (T1D). Fecal samples of 30 people with the m.3243 A > G mutation were used for shotgun metagenomic sequencing. The MD group was compared with 60 healthy controls and 60 people with T1D from different datasets, and were matched for age, sex, and BMI. We found that the Bray-Curtis β-diversity of the gut microbiota differed significantly between MD compared to healthy controls and T1D, while there was a non-significant reduction in Shannon α-diversity in the MD group. The gut microbiota of the MD group was characterized by reduced Faecalibacterium prausnitzii, and increased Escherichia coli, Ruminococcus gnavus, and Ruminococcus torques levels compared to healthy controls and T1D. This pattern aligns with microbial signatures reported in inflammatory bowel disease, which is associated with mitochondrial dysfunction in intestinal epithelial cells. Overall, our explorative study suggest that people with the m.3243 A > G mutation exhibit a dysbiotic gut microbiota, which may pave the way for future research aimed at developing new therapies, dietary adjustments and their potentials to improve quality of life.