SOD1 deficiency alters gastrointestinal microbiota and metabolites in mice.

Redox imbalance induces oxidative damage and causes age-related pathologies. Mice lacking the antioxidant enzyme SOD1 (Sod1-/-) exhibit various aging-like phenotypes throughout the body and are used as aging model mice. Recent reports suggested that age-related changes in the intestinal environment are involved in various diseases. We investigated cecal microbiota profiles and gastrointestinal metabolites in wild-type (Sod1+/+) and Sod1-/- mice. Firmicutes and Bacteroidetes were dominant in Sod1+/+ mice, and most of the detected bacterial species belong to these two phyla. Meanwhile, the Sod1-/- mice had an altered Firmicutes and Bacteroidetes ratio compared to Sod1+/+ mice. Among the identified genera, Paraprevotella, Prevotella, Ruminococcus, and Bacteroides were significantly increased, but Lactobacillus was significantly decreased in Sod1-/- mice compared to Sod1+/+ mice. The correlation analyses between cecal microbiota and liver metabolites showed that Bacteroides and Prevotella spp. were grouped into the same cluster, and Paraprevotella and Ruminococcus spp. were also grouped as another cluster. These four genera showed a positive and a negative correlation with increased and decreased liver metabolites in Sod1-/- mice, respectively. In contrast, Lactobacillus spp. showed a negative correlation with increased liver metabolites and a positive correlation with decreased liver metabolites in Sod1-/- mice. These results suggest that the redox imbalance induced by Sod1 loss alters gastrointestinal microflora and metabolites.