The gut microbiome as a determinant of diabetes complications susceptibility
The gut microbiome has recently been implicated as an environmentally-acquired epigenetic factor contributing to chronic diseases such as obesity and diabetes. In this pilot project, we propose to test the hypothesis that the composition of the microbiome is a major determinant of the extent to which a diabetes-prone mouse will develop a disease-associated complication (diabetic nephropathy). The mouse model we will use is the FVB –Leprdb/db mouse, that Wang and colleagues at the Albert Einstein College of Medicine (AECM) have described as a model for diabetes-associated nephropathy (11). Under the auspices of the AMDCC, FVB –Leprdb/db mice were brought from AECM to the Jackson Laboratory (JAX) but surprisingly, the diabetic nephropathy was extremely attenuated. These observations raise the possibility that the microbiomes of mice housed at the two facilities differs substantially, and these differences explain differences in diabetic nephropathy between colonies. In this pilot study we propose to investigate the microbiomes of FVB –Leprdb/db and wildtype mice housed at JAX and AECM using high-throughput 16S rRNA gene sequence analysis (using Roche/454 Titanium pyrosequencing and sample barcoding). The approach is designed to assess the importance of the microbiome as a factor in disease progression, rather than demonstrate its role unequivocally: the results of this pilot project will inform if a more intensive investigation into the role of the microbiome in disease phenotype is warranted.

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