Leptin Deficient Obese Mice Tag Encoded 16s rRNA gene pyrosequencing. mouse gut metagenome

Aims and hypothesis. Many laboratory animals are used to study type 2 diabetes mellitus and variation in these lead to the need for larger group sizes to reach high statistical power. Literature indicates that disease is under heavy impact of the gut microbiota, which we therefore hypothesized to be a major source of the variation observed in leptin deficient obese (Lepob/ Lepob) mice. Methods. Twenty four male B6.V-Lepob/J were characterized at the age of 8 and 16 weeks in relation to gut microbiota, oral glucose tolerance, and insulin, weekly by blood glucose and weight, and at the age of 8, 13 and 16 weeks for serum levels of IL-10, IL-12, TNF-α and CRP, as well as HbA1c and the number of regulatory T cells at 16 weeks of age. All the findings were correlated to one another. Results. The gut microbiota at start correlated positively to glycated hemoglobin. Glucose intolerance correlated positively or negatively to the proportions of Prevotellaceae and Lachnospiraceae, respectively. Glucose intolerance, blood glucose, and glycated hemoglobin correlated positively to IL-10, IL-12 and TNF-α. The frequency of regulatory T cells correlated negatively to glucose intolerance and to the gut microbiota end data. Akkermansia muciniphila disappeared with age. Conclusions. It is concluded that the gut microbiota has an impact on long term glucose levels and glucose intolerance in Lepob/Lepob mice, and that these parameters correlate strongly to regulatory and inflammatory immunology.