RESUMEN
Diabetic nephropathy (DN) is a severe complication of diabetes and the leading cause of end-stage renal disease and death. Germacrone (Ger) possesses anti-inflammatory, antioxidant and anti-DN properties. However, it is unclear whether the improvement in kidney damage caused by Ger in DN mice is related to abnormal compositions and metabolites of the gut microbiota. This study generates a mouse model of DN to explore the potent therapeutic ability and mechanism of Ger in renal function by 16S rRNA sequencing and untargeted fecal metabolomics. Although there is no significant change in microbiota diversity, the structure of the gut microbiota in the DN group is quite different. Serratia_marcescens and Lactobacillus_iners are elevated in the model group but significantly decreased after Ger intervention ( P<0.05). Under the treatment of Ger, no significant differences in the diversity and richness of the gut microbiota are observed. An imbalance in the intestinal flora leads to the dysregulation of metabolites, and non-targeted metabolomics data indicate high expression of stearic acid in the DN group, and oleic acid could serve as a potential marker of the therapeutic role of Ger in the DN model. Overall, Ger improves kidney injury in diabetic mice, in part potentially by reducing the abundance of Serratia_marcescens and Lactobacillus_iners, as well as regulating the associated increase in metabolites such as oleic acid, lithocholic acid and the decrease in stearic acid. Our research expands the understanding of the relationship between the gut microbiota and metabolites in Ger-treated DN. This contributes to the usage of natural products as a therapeutic approach for the treatment of DN via microbiota regulation.
Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Lactobacillus , Animales , Ratones , Nefropatías Diabéticas/genética , ARN Ribosómico 16S/genética , Diabetes Mellitus Experimental/genética , Sesquiterpenos de GermacranoRESUMEN
Morus alba L. fruit, a medicinal and edible fruit in East Asia, showed potential health-promoting effects against metabolic syndrome (MetS). However, both the protective effects and mechanisms of different fractions extracted from Morus alba L. fruit against MetS remain unclear. Additionally, the gut microbiota and its metabolites are regarded as key factors in the development of MetS. This study aimed to investigate the potential role of polyphenols and polysaccharides derived from Morus alba L. fruit against MetS in high-fat diet (HFD)-fed mice, individually and in combination, focusing on remodeling effects on gut microbiota and metabolite profiles. In the study, polyphenols and polysaccharides derived from Morus alba L. fruit improved the traditional pharmacodynamic parameters of MetS, including reductions in body weight (BW) and fat accumulation, improvement in insulin resistance, regulation of dyslipidemia, prevention of pathological changes in liver, kidney and proximal colon tissue, and suppressive actions against oxidative stress. In particular, the group treated with polyphenols and polysaccharides in combination showed better efficacy. The relative abundance of beneficial bacterial genera Muribaculum and Lachnospiraceae_NK4A136_group were increased to various degrees, while opportunistic pathogens such as Prevotella_2, Bacteroides, Faecalibacterium and Fusobacterium were markedly decreased after treatments. Moreover, fecal metabolite profiles revealed 23 differential metabolites related to treatments with polyphenols and polysaccharides derived from Morus alba L. fruit, individually and in combination. Altogether, these results demonstrated that polyphenols and polysaccharides derived from Morus alba L. fruit attenuated MetS in HFD-fed mice, and improved the gut microbiota composition and fecal metabolite profiles.
RESUMEN
INTRODUCTION: Consensus in sample preparation for untargeted human fecal metabolomics is lacking. OBJECTIVES: To obtain sample preparation with broad metabolite coverage for high-throughput LC-MS. METHODS: Extraction solvent, solvent ratio and fresh frozen-vs-lyophilized samples were evaluated by metabolite feature quality. RESULTS: Methanol at 5 mL per g wet feces provided a wide metabolite coverage with optimal balance between signal intensity and saturation for both fresh frozen and lyophilized samples. Lyophilization did not affect SCFA and is recommended because of convenience in normalizing to dry matter. CONCLUSION: The suggested sample preparation is simple, efficient and suitable for large-scale human fecal metabolomics.