Prebiotic Mannan-Oligosaccharides Augment the Hypoglycemic Effects of Metformin in Correlation with Modulating Gut Microbiota

Abstract

Type 2 diabetes (T2D) induced by obesity and high-fat diet is significantly associated with gut microbiota dysbacteriosis. Because the first line clinical medicine of metformin has several intestinal drawbacks, combination usage of metformin with a prebiotic of konjac mannan-oligosaccharides (MOS) was conceived and implemented aiming to investigate whether there were some intestinal synergetic effects and how MOS would function. Composite treatment of metformin and MOS demonstrated synergistic effects on ameliorating insulin resistance and glucose tolerance, also on repairing islet and hepatic histology. In addition, MF+MOS altered the gut community composition and structure by decreasing the relative abundances of family Rikenellaceae and order Clostridiales while increasing an unnamed OTU05945 of family S24-7, Akkermansia muciniphila, and Bifidobacterium pseudolongum. The present study suggested that usage of MOS could augment the hypoglycemic effects of metformin in association with gut microbiota modulation, which could provide references for further medication.

Eicosapentaenoic and Docosahexaenoic Acids Differentially Alter Gut Microbiome and Reverse High‐Fat Diet–Induced Insulin Resistance

“…Additionally, in male mice, DHA selectively increased butyrate‐producing Coprococcus [ 47 ] while suppressed pro‐inflammatory species Streptococcus [ 48 ] and p‐75‐a5 which were strongly correlated with HOMA‐IR and LPS production in our study. EPA selectively enriched the abundances of Mucispirillum schaedleri [ 49 ] and Barnesiella [ 50 ] which have been suggested to counteract colitis in mice and elevated S24‐7 [ 51 ] and Barnesiella [ 52 ] linked with ameliorated glucose metabolism, whereas substantially abolished SCFA‐producing Clostridium XlVa [ 53 ] which might explain the unchanged levels of propionate and butyrate in male mice. In female mice, DHA specifically decreased the abundance of pro‐inflammatory Enterorhabdus [ 54 ] and promoted the growth of butyrate‐producing Intestinimonas [ 55 ] and Bacteroides acidifaciens [ 56 ] which were shown to prevent obesity and improve insulin sensitivity.…”

Mannan Oligosaccharide Suppresses Lipid Accumulation and Appetite in Western‐Diet‐Induced Obese Mice Via Reshaping Gut Microbiome and Enhancing Short‐Chain Fatty Acids Production

“…MOS, one of the potent prebiotics, has been widely reported to possess antioxidant, anti‐inflammatory, anti‐atherosclerosis, and anti‐virus bioactivities and to improve STZ‐induced diabetes . Importantly, MOS supplementation could improve the gut microbiota balance and mediate the microbial synthesis of metabolites . A recent report indicated that Konjaku flour attenuated HFD‐induced obesity and gut microbiota imbalance in 3 week weaning mice .…”

“…[20] Importantly, MOS supplementation could improve the gut microbiota balance and mediate the microbial synthesis of metabolites. [26,37,48] A recent report indicated that Konjaku flour attenuated HFD-induced obesity and gut microbiota imbalance in 3 week weaning mice. [26] MOS is one of the major components of Konjaku flour, and its polymerization degree is 2−10.…”

“…The five groups of mice were orally administrated with MOS solution or saline every day, and the intragastrical volume was calculated based on body weight (5 µL g –1 ). The doses of MOS were selected based on previous research and our preliminary experiments . The treatment continued for 4 weeks ( Figure A).…”

“…The doses of MOS were selected based on previous research and our preliminary experiments. [21,26,37,38] The treatment continued for 4 weeks (Figure 1A). The equivalent low and high MOS doses for humans are 10.99 and 21.99 mg kg -1 d -1 , respectively, based on Meeh-Rubner equation.…”