Comparisons of Effects on Intestinal Short-Chain Fatty Acid Concentration after Exposure of Two Glycosidase Inhibitors in Mice

Abstract

Acarbose and voglibose are the most widely used diabetes drugs as glycosidase inhibitors. In this study, the use of these two inhibitors significantly increased the content of starch in large intestine, and altered the concentration of short-chain fatty acids (SCFAs) by affecting the intestinal microbiota. However, there are some differences in the intestinal microbiome of the two groups of mice, mainly in bacteria such as Bacteroidaceae bacteroides and Desulfovibrionaceae desulfovibrio. The productions of acetate and propionate in caecum in voglibose group were significantly higher than those in acarbose group and two kinds of glycosidase inhibitors were close in the production of butyrate in caecum. The Tax4Fun analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) data indicated that different productions of acetate and propionate between acarbose group and voglibose group may be related to 2-oxoisovalerate dehydrogenase and pyruvate oxidase. In addition, in-vitro experiments suggested that voglibose had less effect on epithelial cells than acarbose after direct stimulation. According to the recent researches of SCFAs produced by intestinal microbiota, our comparative study shown higher concentration of these beneficial fatty acids in the lumen of voglibose-treated mice, which implied a lower level of inflammation.Key words acarbose; voglibose; microbiota; short-chain fatty acid; Tax4FunWith the increasing number of obesity and diabetes around the world, there are more and more different classes of medications to treat diabetes, such as biguanides (metformin), sulfonylureas, insulin, glucagon-like peptide 1 (GLP-1) agonists, dipeptidyl peptidase IV inhibitors, thiazolidinediones and sodium-glucose transporter 2 inhibitors (to name a few). 1) However, acarbose and voglibose as part of α-glucosidase inhibitors (AGIs) are another class of anti-diabetic medications. As first-line hypoglycemic drugs used in patients with type 2 diabetes especially in Asian since their diet meals contain high content of carbohydrates, acarbose and voglibose can typically reduce postprandial glucose level by delaying carbohydrate digestion in the gut, so they can be a useful treatment in the patients who raised basal glucose concentrations slightly and marked postprandial hyperglycemia. 2) In addition, there will also be some side effects, mainly reflected in gastrointestinal flatulence, loose stool and so on. The main reason for this is that fermentation of undigested carbohydrates by bacteria produced gas in the colon. 3) Acarbose and voglibose treatment delayed starch digestion in the small intestine but there was compensatory salvage through bacterial fermentation in the large intestine. 4) When carbohydrates (starch, dietary fiber) enter the large intestine, they are degraded by the fermentation of anaerobic flora. 5) Under normal diet situations, the better part of starch was digested and absorbed in the small intestine, therefore, extra starch entering the large bowel changed microbial eco-system to some degree. Som...

Effects of Non-insulin Anti-hyperglycemic Agents on Gut Microbiota: A Systematic Review on Human and Animal Studies

“…Among 15 rodent studies ( 5 , 6 , 36 , 37 , 41 , 47 , 48 , 54 , 56 , 58 , 66 , 69 , 70 , 73 , 75 ) on the phylum Firmicutes , the results were inconclusive among those treated with metformin ( 5 , 36 , 37 , 41 , 47 , 48 , 54 , 56 ), acarbose ( 5 , 58 ), liraglutide ( 66 , 69 , 70 ), and sitagliptin ( 5 , 73 ). The genus Lactobacillus was the focus of 13 studies ( 5 , 35 , 41 – 43 , 47 , 53 , 54 , 58 , 62 , 66 , 70 , 73 ). Six out of the eight studies treated with metformin ( 5 , 35 , 43 , 53 , 54 , 62 ) saw an increase in this genus in mice and rats, while the results in studies treated with acarbose ( 5 , 58 , 62 ), liraglutide ( 66 , 70 ), and sitagliptin ( 5 , 73 ) were inconclusive.…”

“…The genus Lactobacillus was the focus of 13 studies ( 5 , 35 , 41 – 43 , 47 , 53 , 54 , 58 , 62 , 66 , 70 , 73 ). Six out of the eight studies treated with metformin ( 5 , 35 , 43 , 53 , 54 , 62 ) saw an increase in this genus in mice and rats, while the results in studies treated with acarbose ( 5 , 58 , 62 ), liraglutide ( 66 , 70 ), and sitagliptin ( 5 , 73 ) were inconclusive.…”

Microbiota and Diabetes Mellitus: Role of Lipid Mediators

“…They observed that both Acarbose and Voglibose increased butyrate production. Meanwhile, the concentration of propionate and acetate only increased in the group that received Voglibose [ 148 ]. These finds suggest that the effects of Acarbose on health are partially due to the changes generated in the gut microbiota, modifying LPS and SCFA concentration as well as other products from their metabolism.…”

Comparison of therapeutic effects of acarbose and metformin under different β-cell function status in Chinese patients with type 2 diabetes

“…The underlying mechanism of weight reduction by acarbose therapy may include the release of ghrelin and gastric inhibitor peptide (GIP) and the increase of glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and cholecystokinin (CCK) [23]. Furthermore, acarbose may reduce weight by increasing the content of gut Bifidobacterium longum, decreasing some inflammatory cytokines [24], altering the concentration of short-chain fatty acids (SCFAs) [25] and regulating hunger and satiety at the brain level [9,26]. Metformin causes body weight loss by stimulating phosphorylation of adenosine monophosphate activated protein kinase (AMPK) [27].…”