Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of type 2 diabetes. However, the efficacy of OP on the advanced stage of type 2 diabetes has not been investigated, and the relationship between OP and intestinal flora has not been studied. Therefore, in this study, to explore the relieving effects of OP intake on the advanced stage of type 2 diabetes and the regulatory effects of OP on intestinal microbes, diabetic db/db mice (17-week-old) were treated with OP at the dose of 200 mg/kg for 15 weeks. We found that OP has a significant effect in decreasing fasting blood glucose levels, improving glucose tolerance, lowering the homeostasis model assessment–insulin resistance index, restoring histopathological features of tissues, and promoting hepatic protein kinase B activation in db/db mice. Notably, OP modulates gut microbiota at phylum level, increases the relative abundance of Verrucomicrobia and Deferribacteres, and decreases the relative abundance of Bacteroidetes. OP treatment increases the relative abundance of Akkermansia, as well as decreases the relative abundance of Prevotella, Odoribacter, Ruminococcus, and Parabacteroides at genus level. In conclusion, OP may ameliorate the advanced stage of type 2 diabetes through modulating the composition and function of gut microbiota. Our findings provide a promising therapeutic approach for the treatment of advanced stage type 2 diabetes.

Methyl cedryl ether (MCE) is a derivative of cedrol and is widely used as a fragrance compound. The aim of this study was to evaluate the preventative effects of MCE on obesity and related metabolic syndromes and to delineate the mechanisms from the perspective of gut microbiota and white adipose tissues (WAT) transcriptomic profiles. Five-week-old male C57BL/6J mice were randomly assigned into 3 groups and fed with chow diet, high-fat diet (HFD), or HFD supplemented with 0.2% (w/w) MCE for 13 weeks. We found that MCE significantly reduced body weight, inhibited adipocyte hypertrophy, and ameliorated hepatic steatosis under HFD conditions. MCE dietary supplementation downregulated the expression of adipogenesis genes (FAS and C/EBPα) and upregulated the mRNA levels of thermogenesis genes (PGC-1α, PRDM16, UCP1, Cidea, Cytc, and COX4) in epididymal WAT. 16S rRNA sequencing revealed that MCE improved gut microbiota dysbiosis in HFD-fed mice, as manifested by the alteration of strains associated with obesity. Further transcriptome analysis of WAT indicated that MCE dramatically changed the gene expression profiles. Our results demonstrate the anti-obesity effect of MCE under HFD conditions, highlighting the nutraceutical potential of MCE for preventing obesity.

Summary: Traditional farm environments induce protection from allergic diseases. In this study, farm environmental factors were classified into three categories, environmental microbes, soil, and organic matter. To explore the impact of soil and environmental microorganisms on gut microbiota and immune function, mice were fed sterilized soil and inhaling microbes, soil microbes, or non‐sterilized soil. Metagenomic sequencing results showed the intake of sterile soil, that is, inhaling a small amount of soil microbes in the air increased gut microbial diversity and the abundance of type III secretion system (T3SS) genes, and decreased serum immune IgE levels induced by 2‐4‐dinitrofluorobenzene (DNFB). The intake of soil microbes increased the abundance of genes involved in the metabolism of short‐chain fatty acids and amino acid biosynthesis. Meanwhile, the intake of soil increased gut microbial diversity, the abundance of T3SS genes and related infectious elements, and genes associated with the metabolism of short‐chain fatty acids and amino acid biosynthesis, and decreased serum IgE levels. Therefore, soil may be useful as a potential ‘prebiotic’ promoting the reproduction and growth of some intestinal microorganisms that harbour bacterial secretion system genes, especially those of T3SS, whose abundance was positively and significantly correlated with innate immune function of mice.

Cedryl acetate (CA), also called acetyl cedrene, is approved by the FDA as a flavoring or adjuvant to be added to foods. In this study, we aimed to investigate the preventive benefits of CA on obesity and obesity-related metabolic syndrome caused by a high-fat diet (HFD). Three groups of C57BL/6J mice (ten-week-old) were fed Chow, an HFD, or an HFD with CA supplementation (100 mg/kg) for 19 weeks. We observed that CA supplementation significantly reduced weight gain induced by an HFD, decreased the weight of the visceral fat pads, and prevented adipocyte hypertrophy in mice. Moreover, mice in the CA group showed significant improvements in hepatic lipid accumulation, glucose intolerance, insulin resistance, and gluconeogenesis compared with the mice in the HFD group. Since 16S rRNA analysis revealed that the gut microbiota in the CA and HFD groups were of similar compositions at the phylum and family levels, CA may have limited effects on gut microbiota in HFD-fed mice. The beneficial effects on the metabolic parameters of CA were reflected by CA’s regulation of metabolism-related gene expression in the liver (including Pepck, G6Pase, and Fbp1) and the epididymal white adipose tissues (including PPARγ, C/EBPα, FABP4, FAS, Cytc, PGC-1α, PRDM16, Cidea, and COX4) of the mice. In summary, a potent preventive effect of CA on HFD-induced obesity and related metabolic syndrome was highlighted by our results, and CA could be a promising dietary component for obesity intervention.