Living Conditions Alter Ketogenic Diet-induced Metabolic Consequences in Mice through Modulating Gut Microbiota

Many laboratories have demonstrated that the ketogenic diet (KD) can lead to weight loss and reduced fasting glucose levels, while also increasing total serum cholesterol levels. However, it's worth noting that the specific outcomes induced by KD can vary across different research settings. Certain studies have indicated that environmental factors, such as housing conditions and the acidity of drinking water, can influence physiological parameters and gut microbes in mice. Thus, our current study aimed to investigate whether differences in housing conditions and pH levels of drinking water contribute to variations in KD-induced phenotypes and gut microbes. Our findings revealed that mice housed in conventional (CV) conditions experienced more significant weight loss, lower fasting blood glucose levels, and a greater elevation of blood cholesterol levels compared to those in the specific pathogen-free (SPF) condition. Additionally, similar differences were observed when comparing mice fed with non-acidified water versus acidified water. Furthermore, we analyzed cecum content samples using 16S rRNA sequencing to assess gut microbial composition and found that the tested environmental variables also had an impact on the gut microbial composition of KD-fed mice, which was correlated with their phenotypic alterations. In summary, both housing conditions and the pH of drinking water were identified as crucial environmental factors that influenced KD-induced changes in metabolic phenotypes and gut microbes. Our study emphasizes the importance of considering these factors in animal studies related to KD and gut microbes, as well as in other types of animal research.