High fat diet-induced changes in gut microbiota have been linked to intestinal permeability and metabolic endotoxemia, which is related to metabolic disorders. However, the influence of a high-glucose (HGD) or high-fructose (HFrD) diet on gut microbiota is largely unknown. We performed changes of gut microbiota in HGD- or HFrD-fed C57BL/6J mice by 16S rRNA analysis. Gut microbiota-derived endotoxin-induced metabolic disorders were evaluated by glucose and insulin tolerance test, gut permeability, Western blot and histological analysis. We found that the HGD and HFrD groups had comparatively higher blood glucose and endotoxin levels, fat mass, dyslipidemia, and glucose intolerance without changes in bodyweight. The HGD- and HFrD-fed mice lost gut microbial diversity, characterized by a lower proportion of Bacteroidetes and a markedly increased proportion of Proteobacteria. Moreover, the HGD and HFrD groups had increased gut permeability due to alterations to the tight junction proteins caused by gut inflammation. Hepatic inflammation and lipid accumulation were also markedly increased in the HGD and HFrD groups. High levels of glucose or fructose in the diet regulate the gut microbiota and increase intestinal permeability, which precedes the development of metabolic endotoxemia, inflammation, and lipid accumulation, ultimately leading to hepatic steatosis and normal-weight obesity.

Polysaccharides that contain many sugar monomers include starch and non-starch polysaccharides (NSPs) together with resistant starch (RS). Dietary polysaccharides are well known to have a wide range of biological benefits for bowel health. Gut microbiota and their fermentative products, short chain fatty acids (SCFA), which have recently been highlighted as metabolic regulators, are thought to mediate the function of dietary complex carbohydrates and bowel health. We discuss the influence of various polysaccharides on human bowel health and the mechanisms underlying these effects. We also describe their biological effects on intestinal health and the mechanisms underlying their activity; the polysaccharides were divided into three categories: dietary, microbial, and host-derived polysaccharides. Physiological impacts of non-starch polysaccharides (NSPs) and resistant starch (RS), both of which pass through the small intestine nearly intact and can be fermented by gut microbiota in the large intestine, are similar to each other. They exert a wide range of beneficial effects including anti-inflammation, gut epithelial barrier protection, and immune modulation through both microbiota-dependent and -independent mechanisms. Bacterial polysaccharides usually found in the cell wall generally act as immune modulators, and host-derived polysaccharides not only protect host cells from pathogenic microbial neighbors but also affect overall intestinal health via interactions with gut microbes. Considering these observations, further studies on polysaccharides will be important for bowel health.

Eucommia ulmoides Oliv. (EU), also known as Du-Zhong, is a medicinal herb commonly used in Asia to treat hypertension and diabetes. Despite evidence of the protective effects of EU against diabetes, its precise effects and mechanisms of action against advanced glycation end-products (AGEs) are unclear. In this study, we evaluated the effects of EU on AGEs-induced renal disease and explored the possible underlying mechanisms using streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice received EU extract (200 mg/kg) orally for 6 weeks. EU treatment did not change blood glucose and glycated hemoglobin (HbA1c) levels in diabetic mice. However, the EU-treated group showed a significant increase in the protein expression and activity of glyoxalase 1 (Glo1), which detoxifies the AGE precursor, methylglyoxal (MGO). EU significantly upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression but downregulated that of receptor for AGE (RAGE). Furthermore, histological and immunohistochemical analyses of kidney tissue showed that EU reduced periodic acid–Schiff (PAS)-positive staining, AGEs, and MGO accumulation in diabetic mice. Based on these findings, we concluded that EU ameliorated the renal damage in diabetic mice by inhibiting AGEs formation and RAGE expression and reducing oxidative stress, through the Glo1 and Nrf2 pathways.