Nephropathy injury is a prevalent complication observed in individuals with diabetes, serving as a prominent contributor to end-stage renal disease, and the advanced glycation products (AGEs) are important factors that induce kidney injury in patients with diabetes. Addressing this condition remains a challenging aspect in clinical practice. The aim of this study was to explore the effects of Lactiplantibacillus plantarum NKK20 strain (NKK20) which protects against diabetic kidney disease (DKD) based on animal and cell models. The results showed that the NKK20 can significantly reduce renal inflammatory response, serum oxidative stress response, and AGE concentration in diabetic mice. After treatment with NKK20, the kidney damage of diabetic mice was significantly improved, and more importantly, the concentration of butyrate, a specific anti-inflammatory metabolite of intestinal flora in the stool of diabetic mice, was significantly increased. In addition, nontargeted metabolomics analysis showed a significant difference between the metabolites in the mouse serum contents of the NKK20 administration group and those in the nephropathy injury group, in which a total of 24 different metabolites that were significantly affected by NKK20 were observed, and these metabolites were mainly involved in glycerophospholipid metabolism and arachidonic acid metabolism. Also, the administration of butyrate to human kidney- (HK-) 2 cells that were stimulated by AGEs resulted in a significant upregulation of ZO-1, Occludin, and E-cadherin gene expressions and downregulation of α-SMA gene expression. This means that butyrate can maintain the tight junction structure of HK-2 cells and inhibit fibrosis. Butyrate also significantly inhibited the activation of PI3K/Akt pathway. These results indicate that NKK20 can treat kidney injury in diabetic mice by reducing blood glucose and AGE concentration and increasing butyrate production in the intestine. By inhibiting PI3K pathway activation in HK-2 cells, butyrate maintains a tight junction structure of renal tubule epithelial cells and inhibits renal tissue fibrosis. These results suggest that NKK20 is helpful to prevent and treat the occurrence and aggravation of diabetic kidney injury.

This study is aimed at assessing the impact of soluble dietary fiber inulin on the treatment of diabetes‐related chronic inflammation and kidney injury in mice with type 2 diabetes (T2DM). The T2DM model was created by feeding the Institute of Cancer Research (ICR) mice a high‐fat diet and intraperitoneally injecting them with streptozotocin (50 mg/kg for 5 consecutive days). The thirty‐six ICR mice were divided into three dietary groups: the normal control (NC) group, the T2DM (DM) group, and the DM + inulin diet (INU) group. The INU group mice were given inulin at the dose of 500 mg/kg gavage daily until the end of the 12th week. After 12 weeks, the administration of inulin resulted in decreased serum levels of fasting blood glucose (FBG), low‐density lipoprotein cholesterol (LDL‐C), blood urea nitrogen (BUN), and creatinine (CRE). The administration of inulin not only ameliorated renal injury but also resulted in a reduction in the mRNA expressions of inflammatory factors in the spleen and serum oxidative stress levels, when compared to the DM group. Additionally, inulin treatment in mice with a T2DM model led to a significant increase in the concentrations of three primary short‐chain fatty acids (SCFAs) (acetic acid, propionic acid, and butyric acid), while the concentration of advanced glycation end products (AGEs), a prominent inflammatory factor in diabetes, exhibited a significant decrease. The results of untargeted metabolomics indicate that inulin has the potential to alleviate inflammatory response and kidney damage in diabetic mice. This beneficial effect is attributed to its impact on various metabolic pathways, including glycerophospholipid metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Consequently, oral inulin emerges as a promising treatment option for diabetes and kidney injury.

Background: Transferable linezolid resistance determinants in Enterococcus faecium , particularly optrA, poxtA , and cfr , have raised increasing global concern due to their potential dissemination across clinical, animal, food, and environmental reservoirs. However, their population distribution, genomic contexts, and associated virulence backgrounds remain incompletely understood. Methods: We performed a large-scale genomic analysis of 2,235 publicly available E. faecium genomes to investigate the distribution, sequence types (STs), virulence factors (VFs), and genomic contexts of transferable linezolid resistance genes. Phylogenetic analysis and comparative examination of gene flanking regions were conducted to explore the mechanisms underlying resistance gene dissemination. Results: A total of 243 genomes (10.9%) carried at least one linezolid resistance gene. poxtA (8.1%) and optrA (6.9%) were more frequently detected than cfr (2.2%). Multiple resistance determinants were simultaneously observed within individual isolates, with optrA + poxtA representing the most frequent gene combination. These resistance genes were distributed across 90 distinct STs, indicating substantial population diversity. Comparative phylogenetic and genomic context analyses revealed significant genetic diversity and a lack of strict phylogenetic clustering, suggesting that horizontal gene transfer mediated by mobile genetic elements plays a major role in the dissemination of these determinants. VF analysis identified 44 virulence genes, with several adherence-associated genes highly conserved across isolates. Notably, certain adherence-related VFs were enriched in isolates harboring multiple resistance genes. Conclusion: Together, these findings highlight the widespread dissemination of optrA -, poxtA -, and cfr -mediated linezolid resistance in diverse E. faecium genomic backgrounds and underscore the important role of horizontal gene transfer in their spread. Continuous genomic surveillance integrating resistance and virulence analyses will be essential for understanding and controlling the global transmission of linezolid-resistant E. faecium .

Background: The primary reason for the development of chemotherapeutic intestinal mucositis induced by 5-fluorouracil (5-FU) is the activation of macrophages in the mucosa. This study aimed to explore how berberine can alleviate inflammation in macrophages and the resulting intestinal mucosal inflammation in mice induced by 5-FU. Methods: Tohoku Hospital Pediatrics-1 (THP-1) cell inflammatory response and mouse intestinal mucositis were induced by 5-FU and treated with berberine. The levels of inflammation-related factors and autophagy related proteins in THP-1 cells were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting. The concentrations of double-stranded DNA (dsDNA) and interleukin-1β (IL-1β) in mice serum and the small intestine hematoxylin-eosin (HE) staining were used to evaluate intestinal mucosal damage. Immunoglobulin A (IgA), an indicator of mucosal immunity, was detected in mice serum by enzyme-linked immunosorbent assay (ELISA). We used quantitative polymerase chain reaction (qPCR) to detect the relative contents of four important strains (Bifidobacterium, Lactobacillus, Escherichia coli, and Enterococcus) in the colon contents of mice. Additionally, we employed liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS) technique to measure the concentrations of three main short-chain fatty acids (acetic acid, propionic acid, and butyric acid) in the mice's plasma. Furthermore, we employed ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q Tof-MS) technique to analyze the non-targeted metabolomics of mouse serum. Results: Berberine has been found to inhibit the expressions of NOD-Like Receptor Thermal Protein Domain Associated Protein 3 (NLRP3), Caspase-1, and IL-1β in THP-1 cells (p < 0.05). Additionally, it effectively suppresses the expression of autophagy related proteins LC3 and Beclin-1 in THP-1 cells (p < 0.05). Furthermore, in a mouse model study, berberine significantly enhances the levels of beneficial bacteria Bifidobacterium and Lactobacillus, as well as the concentrations of three main short-chain fatty acids (SCFAs) in the plasma of mice (p < 0.05). Moreover, it reduced the concentration of pro-inflammatory factor dsDNA and increased the mucosal immunity index IgA concentration in blood (p < 0.05). The untargeted metabolomics results demonstrated that berberine could regulate the inflammatory response of mice by impacting the metabolism of taurine, glycerol phospholipid, arachidonic acid, and primary bile acid biosynthesis. Conclusions: Berberine has demonstrated its ability to effectively suppress the inflammatory reaction of THP-1 cells induced by 5-FU. Furthermore, it also influences the “intestinal flora-metabolite-inflammation” pathway by regulating the composition of the intestinal flora, increasing the production of SCFAs, reducing the expression of inflammatory factors, and preserving the structural integrity of the intestinal mucosa.