Simple SummaryOur study investigated the mechanisms by which Icaritin (ICT) suppresses prostate cancer (PCa) progression via modulation of the gut microbiome. Using C57BL/6 and TRAMP mouse models, we found that a high-fat diet (HFD) significantly reduced in-testinal Akkermansiaceae abundance and vitamin K2 levels relative to control di-et-fed mice. ICT supplementation in HFD-fed TRAMP mice restored Akkermansiaceae pop-ulations and elevated vitamin K2 levels, concurrently decreasing serum leptin and in-creasing adiponectin concentrations. Direct gavage with Akkermansiaceae similarly elevated vitamin K2 levels, improved adipokine profiles, and extended survival. These findings demonstrate that ICT exerts anti-tumor effects by modulating gut Akker-man-siaceae, thereby enhancing vitamin K2 production and regulating adipokine se-cretion, which supports its clinical potential for PCa treatment.Background:High-fat diet (HFD) induced inflammation and tumorigenesis by altering gut microenvironment and gut microbiome profiles. Vitamin K2 along withAkkermansiaceae, an intestinal symbiote, is involved in anti-tumors including prostate cancer (PCa). Although there have been clinical studies of Icaritin (ICT) for anti-tumor, its detailed mechanism for anti-PCa remains unclear. Here, we explored the effect of ICT on PCa progression that involved altering the mouse gut microbiome.Methods:We used 20 C57BL/6 mice and 85 transgenic adenocarcinomas of mouse prostate (TRAMP) mice as animal models. Then, 16SrRNA pyrophosphate gene sequencing was used to analyze the intestinal fecal microbiome of mice in each group. At the same time, vitamin K2 in fecal samples was determined by High Performance Liquid Chromatography (HPLC), and the content of adipokines leptin and adiponectin in serum was determined by Elisa.Results:It was observed that the relative abundance ofAkkermansiaceae(9.14 ± 2.75% (C57BL/6J-N) vs. 5.66 ± 1.35% (C57BL/6J-HFD); 1.21 ± 0.61% (TRAMP-N) vs. 0.67 ± 0.45% (TRAMP-HFD) (p< 0.05) and vitamin K2 (C57BL/6J-HFD was 0.41-fold to C57BL/6J-N, TRAMP-HFD was 0.71-fold to TRAMP-N) in the intestinal fecal of HFD C57BL/6 and TRAMP were significantly lower than those of control mice. Both the ratio ofAkkermansiaceaeand vitamin K2 in the gut fecal were significantly increased in HFD-fed TRAMP mice supplemented with ICT compared with HFD-fed TRAMP group (p< 0.01). When HFD TRAMP mice were fed withAkkermansiaceaeby gavage, the content of vitamin K2 in the intestinal fecal of the mice was increased, the adipokines leptin in the serum were decreased, but the adiponectin was significantly increased, and the overall survival time of the TRAMP mice was significantly prolonged. Our study shows that ICT rescued the reduction inAkkermansiaceaein the gut microbiota of HFD TRAMP mice. ICT suppresses PCa by modulatingAkkermansiaceaein the gut, increasing vitamin K2, and regulating adipokines leptin and adiponectin secretion.Conclusions:Our study suggested that ICT might regulate abundance ofAkkermansiaceaeto increase vitamin K2 to suppress PCa. This provides theoretical basis and data support for the clinical application of ICT in the treatment of PCa.
To investigate the prebiotic potential of two Laminaria japonica polysaccharide (LJP) fractions with different molecular weights and structures, we conducted in vitro simulated digestion and fermentation with hyperlipidemia-associated human gut microbiota. The results indicated that the LJP fraction with higher molecular weight (HLJP) appeared to have a more complex monosaccharide composition and microstructure than did the LJP fraction with lower molecular weight (LLJP), and both fractions could not be digested by in vitro simulated digestion. After in vitro fermentation, HLJP generated more short-chain fatty acids (SCFAs) and showed stronger ability to regulate core metabolites. Intriguingly, LLJP is better at promoting the proliferation of Akkermansiaceae, while HLJP is more effective in reducing the Firmicutes/Bacteroidetes ratio and increasing the content of Bacteroidaceae and Tannerellaceae. The present study indicates that LLJP and HLJP may have probiotic effects through different approaches and these differences may be related to the molecular weight and structure of the polysaccharides.
Tibetan highland barley fiber (T-Fiber) contains high dietary fiber (DF) and beta-glucose. Highland barley has been shown to reduce the risk of diseases associated with high-fat diets (HFD). In the present research, we studied whether T-Fiber could ameliorate HFD-induced obesity in mice and explored its regulatory effects on intestinal microbes . Our findings revealed that T-Fiber feeding significantly reduced weight gain and dyslipidemia , improved glucose tolerance and insulin resistance, alleviated chronic systemic inflammation, and increased short-chain fatty acids (SCFA) in feces in mice. Histological observations confirmed that T-Fiber alleviated Epididymal fat (EF) and lipid accumulation in the liver. In addition, 16s rRNA sequencing analysis of mice cecum contents showed that T-Fiber restored the HFD-induced gut microbiota. T-Fiber supplementation increased the abundance of potentially beneficial bacteria Muribaculaceae , Akkermansiaceae , and Lachnospiraceae_NK4A136_groups , while significantly reducing the abundance of Bacteroidaceae , Prevotellaceae , Rikenellaceae , and Alloprevotella . Furthermore, the increase in the production of SCFA may be related to the abundance of Lachnospiraceae_NK4A136_group . In conclusion, T-Fiber has some anti-obesity abilities under high-fat feeding and can be developed as a relevant anti-obesity product.
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