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BACKGROUND: Lactobacillus species in gut microbiota shows great promise in alleviation of metabolic diseases. However, little is known about the molecular mechanism of how Lactobacillus interacts with metabolites in circulation. Here, using high nucleoside intake to induce hyperuricemia in mice, we investigated the improvement in systemic urate metabolism by oral administration of L. plantarum via different host pathways. RESULTS: Gene expression analysis demonstrated that L. plantarum inhibited the activity of xanthine oxidase and purine nucleoside phosphorylase in liver to suppress urate synthesis. The gut microbiota composition did not dramatically change by oral administration of L. plantarum over 14 days, indicated by no significant difference in α and ß diversities. However, multi-omic network analysis revealed that increase of L. plantarum and decrease of L. johnsonii contributed to a decrease in serum urate levels. Besides, genomic analysis and recombinant protein expression showed that three ribonucleoside hydrolases, RihA-C, in L. plantarum rapidly and cooperatively catalyzed the hydrolysis of nucleosides into nucleobases. Furthermore, the absorption of nucleobase by intestinal epithelial cells was less than that of nucleoside, which resulted in a reduction of urate generation, evidenced by the phenomenon that mice fed with nucleobase diet generated less serum urate than those fed with nucleoside diet over a period of 9-day gavage. CONCLUSION: Collectively, our work provides substantial evidence identifying the specific role of L. plantarum in improvement of urate circulation. We highlight the importance of the enzymes RihA-C existing in L. plantarum for the urate metabolism in hyperuricemia mice induced by a high-nucleoside diet. Although the direct connection between nucleobase transport and host urate levels has not been identified, the lack of nucleobase transporter in intestinal epithelial cells might be important to decrease its absorption and metabolization for urate production, leading to the decrease of serum urate in host. These findings provide important insights into urate metabolism regulation. Video Abstract.

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We report for the first time the usage of Millettia speciosa Champ cellulose (MSCC) and carboxymethylcellulose (MSCCMC) for the fabrication of 3D-network hydrogel as delivery system for probiotics. The structural features, swelling behavior and pH-responsiveness of MSCC-MSCCMC hydrogels and their encapsulation and controlled-release behavior for Lactobacillus paracasei BY2 (L. paracasei BY2) were mainly studied. Structural analyses demonstrated that MSCC-MSCCMC hydrogels with porous and network structures were successfully synthesized through the crosslinking of -OH groups between MSCC and MSCCMC molecules. An increasing concentration of MSCCMC significantly improved the pH-responsiveness and swelling ability of the MSCC-MSCCMC hydrogel toward neutral solvent. Besides, the encapsulation efficiency (50.38-88.91 %) and release (42.88-92.86 %) of L. paracasei BY2 were positively correlated with the concentration of MSCCMC. The higher the encapsulation efficiency was, the higher the release in the target intestine. However, due to the existence of bile salts, controlled-release behavior decreased the survivor rate and physiological state (degrading cholesterol) of encapsulating L. paracasei BY2. Even so, the number of viable cells encapsulated by hydrogels still reached the minimum effective concentration in the target intestine. This study provides an available reference for the practical application of hydrogels fabricated from the cellulose of the Millettia speciosa Champ plant for probiotic delivery.

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In this study, five strains of lactic acid bacteria (LAB) with excellent cholesterol-lowering ability were screened from fermented foods. The gastrointestinal stress resistance, intestinal adhesion, and bacteriostasis abilities were evaluated to obtain the best LAB. And then, high-cholesterol HepG2 cell model was further prepared to explore the cholesterol-lowering mechanism of the LAB. Finally, pH-sensitive hydrogel prepared by Millettia speciosa Champ. carboxymethyl cellulose and Millettia speciosa Champ. cellulose was first applied to the microencapsulation of LAB. As a result, Lactobacillus paracasei BY2 (LP-BY2) exhibited higher cholesterol-lowering activity, intestinal adhesion, and bacteriostasis abilities compared with other LAB. Furthermore, it was found that LP-BY2 could reduce the cholesterol level by regulating the expression of key genes that involved in cholesterol synthesis (HMGCR and SREBP-2), uptake (LDLR), and outflow (LXR-α, ABCA1, ABCG5, ABCG8, and CYP7A1) in liver. At the same time, microencapsulation significantly enhanced the survival rate and cholesterol-lowering ability of LP-BY2 after gastrointestinal digestion. This study will provide an available reference for the application of Lactobacillus in prevention and treatment of hypercholesterolemia.