1 research outputs found
High Fat Diet and High Sucrose Intake Divergently Induce Dysregulation of Glucose Homeostasis through Distinct Gut Microbiota-Derived Bile Acid Metabolism in Mice
A high
calorie diet such as excessive fat and sucrose intake is
always accompanied by impaired glucose homeostasis such as T2DM (type
2 diabetes mellitus). However, it remains unclear how fat and sucrose
individually affect host glucose metabolism. In this study, mice were
fed with high fat diet (HFD) or 30% sucrose in drinking water (HSD)
for 24 weeks, and glucose metabolism, gut microbiota composition,
as well as bile acid (BA) profile were investigated. In addition,
the functional changes of HFD or HSD-induced gut microbiota were further
verified by fecal microbiota transplantation (FMT) and ex
vivo culture of gut bacteria with BAs. Our results showed
that both HFD and HSD caused dysregulated lipid metabolism, while
HFD feeding had a more severe effect on impaired glucose homeostasis,
accompanied by reduced hyocholic acid (HCA) levels in all studied
tissues. Meanwhile, HFD had a more dramatic influence on composition
and function of gut microbiota based on α diversity indices,
β diversity analysis, as well as the abundance of secondary
BA producers than HSD. In addition, the phenotypes of impaired glucose
homeostasis and less formation of HCA caused by HFD can be transferred
to recipient mice by FMT. Ex vivo culture with gut
bacteria and BAs revealed HFD-altered gut bacteria produced less HCA
than HSD, which might closely associate with reduced relative abundance
of C7 epimerase-coding bacteria g_norank/unclassified_f_Eggerthellaceae and bile salt hydrolase-producing bacteria Lactobacillus and Bifidobacterium in HFD group. Our findings
revealed that the divergent effects of different high-calorie diets
on glucose metabolism may be due to the gut microbiota-mediated generation
and metabolism of BAs, highlighting the importance of dietary management
in T2DM