Abstract
Background The pathogenesis of spontaneously diabetic Otsuka Long-Evans
Tokushima Fatty (OLETF) rats, among the best models for human type 2 diabetes
mellitus (T2DM), remains poorly defined. Therefore, we investigated the dynamic
changes in taurine-conjugated bile acids (T-BAs) and intestinal microbiota
during T2DM development in OLETF rats.
Methods OLETF rats and corresponding diabetes-resistant Long Evans
Tokushima Otsuka (LETO) rats were fed a normal baseline diet. The progress of
T2DM was divided into four phases, including normal glycemia-normal insulinemia
(baseline), normal glycemia-hyperinsulinemia, impaired glucose tolerance, and
DM. Body weight, liver function, blood lipids, fasting plasma glucose, fasting
plasma insulin, fasting plasma glucagon-like peptide (GLP)-1 and GLP-2, serum
and fecal T-BAs, and gut microbiota were analyzed during the entire course of
T2DM development.
Results There were reductions in fecal T-BAs and short-chain fatty acids
(SCFAs)-producing bacteria including Phascolarctobacterium and
Lactobacillus in OLETF rats compared with those in LETO rats at
baseline, and low levels of fecal T-BAs and SCFAs-producing bacteria were
maintained throughout the whole course of the development of T2DM among OLETF
rats compared with those in corresponding age-matched LETO rats. Fecal
taurine-conjugated chenodeoxycholic acid correlated positively with
Phascolarctobacterium. Fecal taurine-conjugated deoxycholic acid
correlated positively with Lactobacillus and fasting plasma GLP-1 and
inversely with fasting plasma glucose.
Conclusion The fecal BAs profiles and microbiota structure among OLETF
rats were different from those of LETO rats during the entire course of T2DM
development, indicating that reductions in intestinal T-BAs and specific
SCFA-producing bacteria may be potential mechanisms of T2DM in OLETF rats.