Abstract
Rotundic acid (RA) is a major triterpene constituent in the barks of Ilex rotunda Thunb, which have been widely used to make herbal tea for health care in southern China. RA has a variety of bioactivities such as anti-inflammation and lipid-lowering effect. However, little is known about the effects and mechanisms of RA on metabolic disturbance in type 2 diabetes (T2D) and its effect on gut microbiota. A T2D rat model induced by high fat diet (HFD) feeding and low-dose streptozotocin (STZ) injection was employed and RA showed multipronged effects on T2D and its complications, including improving glucolipid metabolism, lowering blood pressure, protecting against cardiovascular and hepatorenal injuries, and alleviating oxidative stress and inflammation. Furthermore, 16s rRNA gene sequencing was carried out on an Illumina HiSeq 2500 platform and RA treatment could restore the gut microbial dysbiosis in T2D rats to a certain extent. RA treatment significantly enhanced the richness and diversity of gut microbiota. At the genus level, beneficial or commensal bacteria Prevotella, Ruminococcus, Leuconostoc and Streptococcus were significantly increased by RA treatment, while RA-treated rats had a lower abundance of opportunistic pathogen Klebsiella and Proteus. Spearman’s correlation analysis showed that the abundances of these bacteria were strongly correlated with various biochemical parameters, suggesting that the improvement of gut microbiota might help to prevent or attenuate T2D and its complication. In conclusion, our findings support RA as a nutraceutical agent or plant foods rich in this compound might be helpful for the alleviation of T2D and its complications through improving gut microbiota.
Highlights
Type 2 diabetes (T2D), which is characterized by low-grade inflammation, insulin resistance and pancreatic β-cell dysfunction, has become a major public health issue worldwide [1]
Rotundic acid (RA) treatment decreased water intake and increased food intake in the T2D rats when compared with the T2D model group (p < 0.05) in the last week of the whole experimental period
With the control group after 6 weeks of high-fat diet (HFD) feeding (p < 0.05) and the STZ injection caused an expected decrease in body weight (p < 0.01), while at the end of this experiment, the RA-treated group had an increased body weight compared with the T2D model group (p < 0.01)
Summary
Type 2 diabetes (T2D), which is characterized by low-grade inflammation, insulin resistance and pancreatic β-cell dysfunction, has become a major public health issue worldwide [1]. Emerging evidence suggests that gut microbiota plays a vital role in intestinal immunity, host metabolism and the development of various diseases, including T2D and diabetic complications. The gut microbial compositions in T2D patients with coronary artery diseases were significantly associated with the increase in the serum level of trimethylamine oxide, which has been suggested to be a microbiota-dependent metabolite to mediate the development of T2D [7,8]. A high-fiber diet containing traditional Chinese medicinal foods such as tartary buckwheat and adlay induced changes in the entire gut microbial community and alleviated T2D via the production of short-chain fatty acids (SCFAs) [9]. For the development of nutraceutical food, these studies suggest that gut microbiota may be a door opened to the prevention and alleviation of T2D and diabetic complications
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