Affiliation:
1. Department of Endocrinology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
Abstract
ABSTRACT
Long-term/high-dose glucocorticoid (GC) use results in glycolipid metabolism disorder, which severely limits its clinical application. The role of the gut microbiota and its metabolites in GC-induced glycolipid metabolism disorder remains unclear. Our previous human study found that obvious gut microbiota dysbiosis characterized by an increasing abundance of
Proteobacteria
and a decreased abundance of
Lachnospiraceae
and
Faecalibacterium
were observed in patients with endogenous hypercortisolism. In this study, we established a mouse model of GC-induced glycolipid metabolism disorder (Dex group) and found that the relative abundances of
Proteobacteria
and
Parasuttrerella
were increased, while the abundances of
Lachnospiraceae
,
Faecalibacterium
, and
Lachnospiraceae_NK4A136_group
were decreased significantly in the Dex group. Compared with the control group, serum total short-chain fatty acids (SCFAs), acetic acid, propionic acid, and GLP-1 levels were all decreased in the Dex group. The mRNA expression of the GPR41 receptor and Pcsk1 in the colon was significantly decreased in the Dex group. Furthermore, GC-induced glycolipid metabolism disorder could be alleviated by depletion of the gut microbiota or fecal bacteria transplantation with control bacteria. The abundances of
Lachnospiraceae_NK4A136_group
and the serum GLP-1 levels were significantly increased, while the abundances of
Proteobacteria
and
Parasutterella
were significantly decreased after fecal bacteria transplantation with control bacteria. Our work indicates that gut microbiota dysbiosis and decreased levels of serum acetic acid and propionic acid may participate in GC-induced glycolipid metabolism disorder. These findings may provide novel insights into the prevention and treatment of GC-induced metabolic disorders.
IMPORTANCE
The role of the gut microbiota in glucocorticoid (GC)-induced glycolipid metabolism disorder remains unclear. In our study, gut microbiota dysbiosis characterized by an increased abundance of
Proteobacteria
/
Parasuttrerella
and a decreased abundance of Lachnospiraceae_NK4A136_group was observed in mice with GC-induced glycolipid metabolism disorder. Some bacteria were shared in our previous study in patients with endogenous hypercortisolism and the mouse model used in the study. Furthermore, the depletion of the gut microbiota and fecal bacteria transplantation with control bacteria could alleviate GC-induced glycolipid metabolism disorder. Plasma acetic acid, propionic acid, and GLP-1 and the mRNA expression of the GPR41 receptor and Pcsk1 in the colon were decreased significantly in mice with GC-induced glycolipid metabolism disorder, which indicated that the gut microbiota/SCFA/GPR41/GLP-1 axis may participate in GC-induced glycolipid metabolism disorder. Our findings indicate that the gut microbiota may serve as a novel therapeutic target for GC-related metabolic disorders.
Funder
MOST | National Natural Science Foundation of China
National Natural Science Foundation of China Hunan Province
Research Project of Hunan Health Committee
Publisher
American Society for Microbiology