Diabetes mellitus is associated with gut microbiota disturbance and intestinal mucosal injuries. This study investigated the influence of propolis on the gut microbiota and intestinal mucosa in rats with diabetes. Sprague-Dawley (SD) rats were randomly assigned to the control group, model group, and three propolis groups (supplemented with 80, 160, and 240 mg/kg·bw propolis, respectively). A high-fat diet combined with a streptozotocin (STZ) abdominal injection were used to induce diabetes in the rats. After 4 weeks, the intestinal histopathological analysis of the ileum was observed by transmission electron microscopy. The fasting blood glucose (FBG), plasma insulin, glucose tolerance (OGTT) and glycosylated hemoglobin (HbA1c) levels were measured. The expression of tight junction (TJ) proteins in the ileum was measured using western blotting. The molecular ecology of the fecal gut microbiota was analyzed by 16S rDNA high-throughput sequencing. The contents of the short-chain fatty acids (SCFAs) in feces were measured using high-performance liquid chromatography (HPLC). After propolis treatment, compared to the model group, FBG and HbA1c levels declined, while the glucose tolerance and insulin sensitivity index (ISI) increased. The levels of TJ proteins in the ileum increased in the propolis groups. The tight junctions and gap junctions of the intestinal epithelium were also improved in the propolis groups. The contents of the feces acetic acid, propionic acid and butyrate were increased in the propolis groups. 16S rDNA high-throughput sequencing revealed that the composition of the gut microbiota of rats in the propolis supplement group was significantly improved. Compared to the model group, propolis exerted hypoglycemic effects in diabetic rats, and it repaired intestinal mucosal damage, benefited the communities of the gut microbiota and increased SCFA levels in diabetic rats.

Aplysin, a kind of phytochemicals or phytonutrients, is purified from red alga Laurencia tristicha. The present study aims to investigate the influence of aplysin on changes of intestinal permeability and microbiota induced by excessive ethanol and iron. Thirty male rats were randomly divided into three groups (10/group): control group (normal saline); ethanol + iron group as EI treated with ethanol (8–12 mL/kg/day) and iron (1000 mg/kg) in diet; EI supplemented with aplysin (150 mg/kg/day) group as AEI; the trial lasts for 12 weeks. The result showed that levels of plasma endotoxin, fatty acid-binding protein 2, D-lactic acid, diamine oxidase were increased in rats in the EI group; and significantly decreased by 14%, 17%, 26%, 16%, respectively (p < 0.05) in the AEI group after the 12-week aplysin treatment. Moreover, in the AEI group the amount of Escherichia coli and Bacteroides fragilis were higher, while the amount of Lactobacillus, Bifidobacterium and Clostridium were lower than those in the EI group. The expressions of iron transporters divalent-metal transporter 1(DMT1) and ferroportin 1(FPN1) were significantly upregulated in the EI group compared to those in the control group. In conclusion, aplysin could effectively improve intestinal permeability and intestinal flora disorder induced with excessive ethanol and iron.

Hypercholesteremia results in cognitive decline, while higher intakes of marine n-3 polyunsaturated fatty acids (PUFA) can ameliorate mild cognitive impairment (MCI). However, whether individual n-3 PUFA, notably docosahexaenoic acid (DHA, C22:6n-3) and eicosapentaenoic acid (EPA, C20:5n-3) have different efficiency to ameliorate MCI remain ambiguous. This study aimed to investigate the underlying mechanism why DHA had superior functions to ameliorate MCI. Here, a case-control study with 1:2 case-to-control ratio was implemented. It showed that serum ceramide concentrations were significantly higher in MCI patients compared with healthy controls, and were negatively associated with DHA composition in erythrocyte phospholipids. The MCI model was established with male C57BL/6J wild-type mice fed a high-fat and high-cholesterol diet (HFD), and administration of DHA led to ameliorated cognitive behavior abnormalities and neuronal apoptosis. The improvement of MCI phenotype was further recapitulated in low-density lipoprotein receptor knockout (LDLR^-/-) mice treated with DHA. Mechanistically, DHA could remodel composition of phospholipid membranes, leading to reduced endocannabinoid ligands and inhibited cannabinoid receptor 1 (CB1). The restrained endocannabinoid system was bound up with inhibited ceramide-induced apoptosis of neurons. This work reveals a novel mechanism, namely CB1-ceramide axis, through which DHA exhibits a alleviation in HFD-induced MCI.