Multiomics Approach to Explore the Amelioration Mechanisms of Glucomannans on the Metabolic Disorder of Type 2 Diabetic Rats

Type 2 diabetes (T2D) is a worldwide
epidemic associated with metabolic
disorders and intestinal microbiota alterations. Polysaccharides have
been considered to be beneficial to the prevention and alleviation
of T2D. In the present study, ultra-performance liquid chromatography–triple-time-of-flight-based
metabolomics and proteomics and 16S rRNA sequencing methods were employed
to evaluate the effects of glucomannans from Dendrobium
officinale stem, konjac, and Aloe vera leaves on host metabolism and intestinal microbiota regulation in
type 2 diabetic rats and potential mechanisms. The metabolism of amino
acids was significantly disturbed in the type 2 diabetic rats, especially
the upregulated branched-chain amino acid (BCAA) metabolism. Host-derived
BCAA metabolism was significantly decreased in type 2 diabetic rats.
However, the levels of BCAAs in host circulation and gene abundance
of BCAA biosynthesis in gut microbiota were significantly increased
in diabetic rats, which suggested that the disturbed intestinal microbiota
might be responsible for the increased circulation of BCAAs in T2D.
Glucomannan treatment decreased the abundance of microbial BCAA biosynthesis-related
genes and ameliorated the host BCAA metabolism. Also, glucomannan
with a higher molecular weight and a lower ratio of mannose/glucose
possessed better antidiabetic effects. In summary, the antidiabetic
effects of glucomannans might be associated with the amelioration
of BCAA metabolism by modulating intestinal microbiota.