Microbial extracellular vesicles contribute to antimicrobial resistance.

With the escalating global antimicrobial resistance crisis, there is an urgent need for innovative strategies against drug-resistant microbes. Accumulating evidence indicates microbial extracellular vesicles (EVs) contribute to antimicrobial resistance. Therefore, comprehensively elucidating the roles and mechanisms of microbial EVs in conferring resistance could provide new perspectives and avenues for novel antimicrobial approaches. In this review, we systematically examine current research on antimicrobial resistance involving bacterial, fungal, and parasitic EVs, delineating the mechanisms whereby microbial EVs promote resistance. Finally, we discuss the application of bacterial EVs in antimicrobial therapy.

Comprehensiveness cuproptosis related genes study for prognosis and medication sensitiveness across cancers, and validation in prostate cancer.

Cuproptosis-related genes (CRGs) are important for tumor development. However, the functions of CRGs across cancers remain obscure. We performed a pan-cancer investigation to reveal the roles of CRGs across cancers. In an analysis of 26 cancers, 12 CRGs were differentially expressed, and those CRGs were found to have prognostic value across different cancer types. The expression of CRGs exhibited varied among tumors of 6 immune subtypes and were significantly correlated with the 16 sensitivities of drugs. The expression of CRGs were highly correlated with immunological subtype and tumor microenvironment (TME) of prostate cancer. We also established CRGs-related prognostic signatures that closely correlated with prognosis and drug sensitivity of prostate cancer patients. Single-cell RNA-seq revealed that several CRGs were enriched in the cancer cells. Finally, an in vitro experiment showed that elesclomol, a cuproptosis inducer, targets ferredoxin 1 and suppress cell viability in prostate cancer cells. In conclusion, we carried out a comprehensive investigation for determining CRGs in differential expression, prognosis, immunological subtype, TME, and cancer treatment sensitivity across 26 malignancies; and validated the results in prostate cancer. Our research improves pan-cancer knowledge of CRGs and identifies more effective immunotherapy strategies.

Impact of coexisting type 2 diabetes mellitus on the urinary microbiota of kidney stone patients.

Objectives: Type 2 diabetes mellitus (T2DM) commonly complicates kidney stone disease (KSD). Our objective is to investigate the variations in the urinary microbiota between individuals with KSD alone and those with KSD plus T2DM. This exploration could have implications for disease diagnosis and treatment strategies. Methods: During lithotripsy, a ureterscope was employed, and 1 mL of urine was collected from the renal pelvis after bladder disinfection. Sequencing targeting the V3-V4 hypervariable region was performed using the 16S rRNA and Illumina Novaseq platform. Results: The Shannon index showed a significant decrease in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.041). Principal Coordinate Analysis (PCoA) demonstrated a distinct bacterial community in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.027). The abundance of Sphingomonas, Corynebacterium, and Lactobacillus was significantly higher in the KSD plus T2DM group than in the KSD-only group (false discovery rate < 0.05). Furthermore, Enhydrobacter, Chryseobacterium, and Allobaculum were positively correlated with fasting blood glucose and HbA1c values (P < 0.05). Conclusions: The urinary microbiota in the renal pelvis exhibits differences between patients with KSD plus T2DM and those with KSD alone. Further studies employing animal models are necessary to validate these distinctions, potentially paving the way for therapeutic developments based on the urinary microbiota.

Comparison of Percutaneous Transforaminal Endoscopic Decompression and Full Endoscopic Lamina Fenestration Decompression in the Treatment of Degenerative Lumbar Spinal Stenosis with Unilateral Radicular Pain: A Retrospective Study.

BACKGROUND: Endoscopic decompression of the spinal canal is an emerging procedure for the treatment of degenerative lumbar spinal stenosis, but there are few reports of comparative studies of endoscopic techniques for transforaminal and non-transforaminal approaches. OBJECTIVE: To compare the clinical application of percutaneous transforaminal endoscopic decompression (PTED) and full endoscopic lamina fenestration decompression (Endo-LOVE) for treating degenerative lumbar spinal stenosis with unilateral radicular pain. METHODS: A total of 58 patients with degenerative lumbar spinal stenosis (DLSS) with unilateral radicular pain in the lower extremities who underwent endoscopic decompression treatment from June 2020 to December 2021 were retrospectively identified and divided into two groups (PTED vs Endo-LOVE). The two groups' perioperative data were analyzed according to surgical modalities. The Visual Analogue Score (VAS) for pain, Oswestry Disability Index (ODI), modified MacNab criteria, and dural sac cross-sectional area (DSCSA) were used to assess the post-operative outcomes of the two groups. RESULTS: All 58 patients completed the operation and received more than 12 months of follow-up. There was no significant difference in the operation time, number of intraoperative fluoroscopies, intraoperative bleeding, or postoperative hospitalization time between the two groups (p > 0.05); VAS scores and ODIs of the two groups at all postoperative time points were significantly lower than before the operation (p < 0.05), and there was no significant difference in the comparison of the clinical efficacy between the two groups (p > 0.05); the DSCSA of the two groups at the last postoperative follow-up was significantly larger than before the operation (p < 0.05), and there was no significant difference in the improvement of DSCSA between them (p > 0.05). CONCLUSIONS: Both procedures are safe and effective in the treatment of DLSS with unilateral lower extremity radicular pain, and we should be specific about the choice of spinal stenosis treatment.

Recent progresses in the late stages of autophagy.

Autophagy, a lysosome-dependent degradation process, plays a crucial role in maintaining cell homeostasis. It serves as a vital mechanism for adapting to stress and ensuring intracellular quality control. Autophagy deficiencies or defects are linked to numerous human disorders, especially those associated with neuronal degeneration or metabolic diseases. Yoshinori Ohsumi was honored with the Nobel Prize in Physiology or Medicine in 2016 for his groundbreaking discoveries regarding autophagy mechanisms. Over the past few decades, autophagy research has predominantly concentrated on the early stages of autophagy, with relatively limited attention given to the late stages. Nevertheless, recent studies have witnessed substantial advancements in understanding the molecular intricacies of the late stages, which follows autophagosome formation. This review provides a comprehensive summary of the recent progresses in comprehending the molecular mechanisms of the late stages of autophagy.

Lamin B1: a novel biomarker in adult and pediatric adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a malignancy with a poor prognosis and high mortality rate. A high tumor mutational burden (TMB) has been found to be associated with poor prognosis in ACC. Thus, exploring ACC biomarkers based on TMB holds significant importance for patient risk stratification. In our research, we utilized weighted gene coexpression network analysis and an assay for transposase-accessible chromatin with high-throughput sequencing to identify genes associated with TMB. Through the comprehensive analysis of various public datasets, Lamin B1 (LMNB1) was identified as a biomarker associated with a high TMB and low chromatin accessibility. Immunohistochemical staining demonstrated high expression of LMNB1 in ACC compared to noncancerous tissues. Functional enrichment analyses revealed that the function of LMNB1 is associated with cell proliferation and division. Furthermore, cell assays suggested that LMNB1 promotes tumor proliferation and invasion. In addition, mutation analysis suggested that the high expression of LMNB1 is associated with TP53 mutations. Additionally, LMNB1 was highly expressed in the vast majority of solid tumors across cancers. In our immune analysis, we discovered that the high expression of LMNB1 might suppress the infiltration of CD8+ T cells in the ACC microenvironment. In summary, LMNB1 is a predictive factor for the poor prognosis of adult and pediatric ACC. Its high expression in ACC is positively associated with high TMB and lower chromatin accessibility, and it promotes ACC cell proliferation and invasion. Therefore, LMNB1 holds promise as a novel biomarker and potential therapeutic target for ACC.

Analyte-induced laccase-mimicking activity inhibition and conductivity enhancement of electroactive nanozymes for ratiometric electrochemical detection of thiram.

Most nanozyme-based electrochemical sensing strategies depend on the catalytic formation of electroactive substances, while the electrochemical properties of nanozymes have rarely been explored. In this study, magnetic nanoparticles encapsulated metal-organic framework served as precursors to prepare bioinspired nanozymes with both laccase-mimicking activity and electroactivity. Owing to the strong affinity between thiram (THR) and Cu(II) active sites in the nanozymes, the binding of THR inhibited nanozyme catalytic activity toward catechol (CT) oxidation and enhanced nanozyme conductivity. A lower oxidation current (ICT) of CT was accompanied by a higher oxidation signal (ICu) of Cu(II), allowing a ratiometric electrochemical response of the electroactive nanozymes toward the incoming THR. The signal ratio (ICu/ICT) displayed a good linear relationship over a THR concentration range of 10.0 nM-3.0 µM with a limit of detection of 0.15 nM, and the entire THR detection process was rapidly accomplished within 5 min. The high sensitivity and selectivity of the developed electrochemical strategy guaranteed the reliable detection of THR in fruit, vegetable, and river water samples. This study provides new insights into the development of nanozymes for electrochemical analysis.

SETD4 inhibits prostate cancer development by promoting H3K27me3-mediated NUPR1 transcriptional repression and cell cycle arrest.

The suppressor of variegation enhancer of zeste-trithorax (SET) domain methyltransferases have been reported to function as key regulators in multiple tumor types by catalyzing histone lysine methylation. Nevertheless, our understanding on the role of these lysine methyltransferases, including SETD4, in prostate cancer (PCa) remains limited. Hence, the specific role of SETD4 in PCa was investigated in this study. The expression of SETD4 in PCa cells and tissue samples was downregulated in PCa cells and tissue specimens, and decreased SETD4 expression led to inferior clinicopathological characteristics in patients with PCa. knockdown of SETD4 facilitated the proliferation of PCa cells and accelerated cell cycle progression. Mechanistically, SETD4 repressed NUPR1 transcription by methylating H3K27 to generate H3K27me3, subsequently inactivated Akt pathway and impeded the tumorigenesis of PCa. Our results highlight that SETD4 prevents the development of PCa by catalyzing the methylation of H3K27 and suppressing NUPR1 transcription, subsequently inactivating the Akt signaling pathway. The findings suggest the potential application of SETD4 in PCa prognosis and therapeutics.

Bio-based Low-k Polymers at High Frequency Derived from Anethole: Synthesis and the Relationship between the Structures and the Properties.

Bio-based polymers have been widely investigated as sustainable low dielectric (low-k) materials in past decades. Nevertheless, a few of the polymers with excellent comprehensive properties have been achieved to satisfy the requirements of high-frequency communication application. In this paper, two fluorinated monomers (BCB-F and 2BCB-F) have been designed and successfully prepared from biomass anethole. The thermal-cross-linkable benzocyclobutene and polyfluorobenzene groups were introduced in order to obtain low-k polymers with good comprehensive properties. A control monomer C1 was prepared from the estragole, the isomer of anethole, to study intensively the effect of structures on properties. Among the thermally cured polymers, cured BCB-F with higher fluoride content shows a comparable dielectric constant (Dk) of 2.62 and lower dielectric loss (Df) of 1.31 × 10-3 at a frequency of 10 GHz, as well as better hydrophobic properties with a water uptake of 0.18%. Such good hydrophobic properties enable it to maintain the good dielectric properties even after being soaked in boiling water for 96 h. Cured 2BCB-F with bifunctional benzocyclobutene groups displays excellent heat resistance with a high glass transition temperature (Tg) of 408 °C and a low coefficient of thermal expansion (CTE) of 52 ppm/°C in the temperature range 30-300 °C. Cured 2BCB-F also shows good dielectric properties with a Dk of 2.61 and a Df of 2.60 × 10-3 at a frequency of 10 GHz. The good comprehensive properties reveal that the anethole-based polymers are suitable candidates as matrix or encapsulation resins for application in electronics and microelectric fields.

Three-in-one covalent organic framework nanozyme: Self-reporting, self-correcting and light-responsive for fluorescence sensing 3-nitrotyrosine.

Most current redox-type nanozyme-based colorimetric sensing platforms are susceptible to interference from the reductant when using chromogenic probe, and the unstable H2O2 used in the peroxidase-like nanozyme-based systems is prone to difficulty in sensing signal reproducibility, while peroxidase-like nanozyme with oxidase-mimicking activity is easy to bring background interference by O2. Since the strong structural designability of covalent organic frameworks (COFs) endows them great application value in the sensing fields, therefore, we envision the construction a COF oxidase-like nanozyme-based controllable sensing system that integrates self-reporting, self-correcting and light-responsive functions to avoid these affects. Herein, 3-nitrotyrosine (3-NT) biomarker was selected as model analyte. 1,3,5-triformylphloroglucinol (Tp) and 3,6-diaminoacridine (DA) were acted as building monomers of the multifunctional COF nanozyme (termed as TpDA). Owing to the excellent light-responsive oxidase-mimicking property of TpDA, 3-NT can be efficiently oxidized, the inner filter effect (IFE) between TpDA and the 3-NT oxidation product greatly quenches the intrinsic fluorescence of TpDA, making it a controllable self-reporting system for fluorescence turn-off sensing 3-NT. Additionally, the excessive reactive oxygen species (ROS) that generated continuously during photocatalysis can resist the interference of endogenous reductants. This study not only provides new insights to avoid the interference of H2O2, background and reductants from conventional redox-type nanozyme-based colorimetric systems but also opens avenues to rational construct versatile COF nanozyme-based sensor.

Can antibiotics for enteritis or for urinary tract infection disrupt the urinary microbiota in rats?

Background: To establish antibiotic preregimes and administration routes for studies on urinary microbiota. Methods and materials: Antibiotics for enteritis (Abx-enteritis) and UTIs (Abx-UTI) were administered via gavage and/or urinary catheterisation (UC) for 1 and/or 2 weeks. The effects of these Abx on the urinary microbiota of rats were examined via 16S rRNA sequencing and urine culture, including anaerobic and aerobic culture. Additionally, the safety of the Abx was examined. Results: Abx-enteritis/Abx-UTI (0.5 g/L and 1 g/L) administered via gavage did not alter the microbial community and bacterial diversity in the urine of rats (FDR > 0.05); however, Abx-UTI (1 g/L) administered via UC for 1 and 2 weeks altered the urinary microbial community (FDR < 0.05). Rats administered Abx-UTI (1 g/L) via UC for 1 week demonstrated a distinct urinary microbiota in culture. Abx-enteritis/Abx-UTI administered via gavage disrupted the microbial community and reduced bacterial diversity in the faeces of rats (FDR < 0.05), and Abx-UTI administered via UC for 2 weeks (FDR < 0.05) altered the fecal microbiota. Abx-UTI (1 g/L) administered via UC did not alter safety considerations. In addition, we noticed that UC did not induce infections and injuries to the bladder and kidney tissues. Conclusions: Administration of Abx-UTI via UC for 1 week can be considered a pre-treatment option while investigating the urinary microbiota.

3D C-Co-N-anchored MWCNTs derived from metal-organic frameworks as high-performance electrochemical sensing platforms for the sensitive detection of adrenaline.

Metal-organic frameworks (MOFs) are composed of metal ions and organic ligands with high specific surface areas, controllable porous structures and abundant metal active sites, showing their extraordinary potential in electrochemical sensors. Here, a 3D conductive network structure (C-Co-N@MWCNTs) is designed by anchoring zeolite imidazole frameworks (ZIF-67) onto multi-walled carbon nanotubes (MWCNTs) and carbonizing them. The C-Co-N@MWCNTs exhibit excellent electron conductivity, a porous structure and considerable electrochemical active sites, which can effectively demonstrate high sensitivity and selectivity in the detection of adrenaline (Ad). The Ad sensor exhibited a low detection limit of 6.7 nmol L-1 (S/N = 3) and a wide linear range of 0.02 µmol L-1-1.0 mmol L-1. The developed sensor also displayed high selectivity, good reproducibility and repeatability. The C-Co-N@MWCNTs electrode was further employed in the detection of Ad in a real sample of human serum, suggesting that it is a promising candidate for electrochemical sensing of Ad.

Development and validation of a tobacco smoking-related index for predicting overall survival and immunotherapy response in bladder cancer.

Bladder cancer is one of the top five most prevalent cancers in the United States and a major cause of cancer-related mortality worldwide. Meanwhile, tobacco smoking is a well-established modifiable risk factor for bladder cancer, with a population-attributable risk of approximately 50%. But the relationship between the prognosis of bladder cancer and tobacco smoking remains unclear. To further explore the potential relationship between tobacco smoking and bladder cancer prognosis, the bladder cancer dataset from The Cancer Genome Atlas Program was used to build a tobacco smoking-related signature known as the "smoker index" for prognosis prediction. Additionally, we validated the efficacy of the signature with some external datasets. Finally, we preliminarily verified the role of CGB5, the hub gene in the smoker index, through pan-cancer analysis and in vitro assays. The study digs into the underlying connection between tobacco smoking and the prognosis of bladder cancer from a multi-omics perspective.

A pan-cancer analysis of DDR1 in prognostic signature and tumor immunity, drug resistance.

Disk-like domain receptor 1 (DDR1) is a crucial regulator of pro-inflammatory mediators and matrix-degrading enzymes. Although mounting evidence supports a vital role for DDR1 in the tumorigenesis of some cancers, no pan-cancer analysis of DDR1 has been reported. Therefore, we aimed to explore the prognostic value of DDR1 in 33 cancer types and investigate its potential immune function. We used a range of bioinformatics approaches to explore the potential carcinogenic role of DDR1 in multiple cancers. We found that DDR1 was expressed at high levels in most cancers. DDR1 expression was positively or negatively associated with prognosis in different cancers. DDR1 expression was significantly associated with DNA methylation in 8 cancers, while there was a correlation between DDR1 expression and RNA methylation-related genes and mismatch repair gene in most cancers. Furthermore, DDR1 expression was significantly associated with microsatellite instability in 6 cancers and tumor mutation burden in 11 cancers. In addition, DDR1 expression was also significantly correlated with immune cell infiltration, tumor microenvironment, immune-related genes, and drug resistance in various cancers. In conclusion, DDR1 can serve as a potential therapeutic target and prognostic marker for various malignancies due to its vital role in tumorigenesis and tumor immunity.

Boron Exposure Assessment of Desalinated Seawater on an Island in China.

This study aimed to investigate the boron level in drinking water and daily boron intake of island residents, and to have a health risk assessment of the boron exposure. One-year water boron surveillance was made through the 18 selected sampling sites (5 finished water and 13 tap water) covered by 5 water treatment plants with different water sources. We recruited 220 healthy volunteers (half men and half women) from 89 families covering all age groups living in Shengshan to provide basic information and living habits. One-third of the families attended the daily food boron intake evaluation through the double meal method for three days. In each family, only one family member provided the food samples. Urine samples were collected from all subjects to get the urine boron level. Furthermore, we used the EPA model and TDI for health risk assessments. The boron level in finished water and tap water with different sources were 0.68-1.46 mg/L and 0.62-1.26 mg/L for desalinated water, 0.30-0.39 mg/L and 0.20-0.50 mg/L for reservoir water, and 0.32-0.43 mg/L and 0.20-0.79 mg/L for mixture water. The average level of water boron intake, diet boron intake, and total boron intake was 0.113 ± 0.127 mg/d, 1.562 ± 0.927 mg/d, 1.674 ± 0.939mg/d, respectively, for the select sampling subjects. There were no significant differences in total boron intake for different age groups (1.685 ± 1.216 mg/d vs. 1.669 ± 0.793 mg/d for <45 yrs vs. ≥45 yrs, p = 0.968) and gender groups (1.754 ± 1.009 mg/d vs. 1.633 ± 0.923 mg/d for male vs. female, p = 0.735). Urine boron concentrations were similar in the two age groups (1.938 mg/g creatinine vs. 1.762 mg/g creatinine for <45 yrs vs. ≥45 yrs, p = 0.635). There were significant differences in urinary boron between males and females (1.569 mg/g creatinine vs. 2.148 mg/g creatinine, p = 0.018). The largest hazard quotient (HQ) of drinking water was 0.31, and the total boron exposures in this population were 0.03 mg/kg bw per day. The study showed that there was no possible non-carcinogenic risk of water boron exposure and lower health risk of total boron exposure to humans in this region, but its toxicity should not be ignored. The subsequent studies should strengthen the analysis of the subgroup populations.

Hsa_circ_0094606 promotes malignant progression of prostate cancer by inducing M2 polarization of macrophages through PRMT1-mediated arginine methylation of ILF3.

Circular RNA (circRNA), a type of noncoding RNAs, has been demonstrated to act vital roles in tumorigenesis and cancer deterioration. Although tumor-associated macrophages are involved in tumor malignancy, the interactions between circRNAs and tumor-associated macrophages in prostate cancer (PCa) remain unclear. In the present study, we found that hsa_circ_0094606 (subsequently named circ_0094606) could promote proliferation, epithelial-mesenchymal transition (EMT) as well as migration of PCa cells through cell viability and migration assays and the determination of EMT markers. Mass spectrometry analysis after RNA pull-down experiment identified that circ_0094606 bound to protein arginine methyltransferase 1 (PRMT1) in PCa cells, and further functional assays revealed that circ_0094606 promoted the malignant progression of PCa by binding to PRMT1. Moreover, co-immunoprecipitation (Co-IP), glutathione-S-transferase (GST) pull-down and immunofluorescence showed that PRMT1 mediated arginine methylation of ILF3 to stabilize the protein. Bioinformatics analysis combined with data from RNA-binding protein immunoprecipitation and RNA pull-down suggested that ILF3 could stabilize IL-8 mRNA, which promoted the M2 polarization in coculture study. Finally, in vivo experiments showed that circ_0094606 subserve PCa growth and promoted the M2 polarization of macrophages through the PRMT1/ILF3/IL-8 regulation pathway, supporting circ_0094606 as a potential novel effective target for PCa treatment.

Ferredoxin 1 is a cuproptosis-key gene responsible for tumor immunity and drug sensitivity: A pan-cancer analysis.

Ferredoxin 1 (FDX1) functions by transferring electrons from NADPH to mitochondrial cytochrome P450 via the ferredoxin reductase and is the key regulator in copper-dependent cell death. Although mounting evidence supports a vital role for FDX1 in tumorigenesis of some cancers, no pan-cancer analysis of FDX1 has been reported. Therefore, we aimed to explore the prognostic value of FDX1 in pan-cancer and investigate its potential immune function. Based on data from The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, Human Protein Atlas, and Gene Set Cancer Analysis, we used a range of bioinformatics approaches to explore the potential carcinogenic role of FDX1, including analyzing the relationship between FDX1 expression and prognosis, DNA methylation, RNA methylation-related genes, mismatch repair (MMR) gene, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME), immune-related genes, and drug sensitivity in different tumors. The results show that FDX1 was lowly expressed in most cancers but higher in glioblastoma multiforme, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. Moreover, FDX1 expression was positively or negatively associated with prognosis in different cancers. FDX1 expression was significantly associated with DNA methylation in 6 cancers, while there was a correlation between FDX1 expression and RNA methylation-related genes and MMR gene in most cancers. Furthermore, FDX1 expression was significantly associated with MSI in 8 cancers and TMB in 10 cancers. In addition, FDX1 expression was also significantly correlated with immune cell infiltration, immune-related genes, TME, and drug resistance in various cancers. An experiment in vitro showed FDX1 is downregulated by elesclomol, resulting in inhibiting cell viability of bladder cancer, clear cell renal cell carcinoma, and prostate cancer cells. Our study reveals that FDX1 can serve as a potential therapeutic target and prognostic marker for various malignancies due to its vital role in tumorigenesis and tumor immunity.

Salivary microbiome in chronic kidney disease: what is its connection to diabetes, hypertension, and immunity?

BACKGROUND: The association between oral dysbiosis and chronic kidney disease (CKD) has gained increasing attention in recent years. Diabetes and hypertension are the most common conditions in CKD. However, a case-control study with matched confounding variables on the salivary microbiome in CKD and the influence of diabetes and hypertension on the microbiome has never been reported. METHODS: In our study, we compared the salivary microbiome profile between patients with CKD and healthy controls (HC) using 16S ribosomal DNA sequencing and examine its association with diabetes, hypertension, and immunity. RESULTS: We observed that the bacterial community was skewed in the saliva of CKD, with increased Lautropia and Pseudomonas, and decreased Actinomyces, Prevotella, Prevotella 7, and Trichococcus. No difference in the bacterial community between the CKD patients complicated with and without diabetes, and between those with and without hypertension. Prevotella 7 declined in CKD patients with/without hypertension with respect to HC, while Pseudomonas increased in CKD patients with/without hypertension. Pseudomonas was negatively associated with immunoglobin G in CKD patients. Both CKD patients with positive and negative antistreptolysin O had declined Prevotella 7 and Trichococcus compared to HC, whereas increased Pseudomonas. CONCLUSIONS: Our study identifies a distinct bacterial saliva microbiome in CKD patients characterized by alteration in composition. We unravel here that the co-occurrence diseases of diabetes and hypertension are not associated with specific bacterial alterations, suggesting that bacterial dysbiosis in saliva plays a role in renal damage regardless of the occurrence of diabetes and hypertension.

The Bladder Microbiome, Metabolome, Cytokines, and Phenotypes in Patients with Systemic Lupus Erythematosus.

Emerging studies reveal unique bacterial communities in the human bladder, with alteration of composition associated to disease states. Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by frequent impairment of the kidney. Here, we explored the bladder microbiome, metabolome, and cytokine profiles in SLE patients, as well as correlations between microbiome and metabolome, cytokines, and disease profiles. We recruited a group of 50 SLE patients and 50 individually matched asymptomatic controls. We used transurethral catheterization to collect urine samples, 16S rRNA gene sequencing to profile bladder microbiomes, and liquid chromatography-tandem mass spectrometry to perform untargeted metabolomic profiling. Compared to controls, SLE patients possessed unique bladder microbial communities and increased alpha diversity. These differences were accompanied by differences in urinary metabolomes, cytokines, and patients' disease profiles. The SLE-enriched genera, including Bacteroides, were positively correlated with several SLE-enriched metabolites, including olopatadine. The SLE-depleted genera, such as Pseudomonas, were negatively correlated to SLE-depleted cytokines, including interleukin-8. Alteration of the bladder microbiome was associated with disease profile. For example, the genera Megamonas and Phocaeicola were negatively correlated with serum complement component 3, and Streptococcus was positively correlated with IgG. Our present study reveals associations between the bladder microbiome and the urinary metabolome, cytokines, and disease phenotypes. Our results could help identify biomarkers for SLE. IMPORTANCE Contrary to dogma, the human urinary bladder possesses its own unique bacterial community with alteration of composition associated with disease states. Systemic lupus erythematosus (SLE) is a complex autoimmune disease often characterized by kidney impairment. Here, we explored the bladder microbiome, metabolome, and cytokine profiles in SLE patients, as well as correlations between the microbiome and metabolome, cytokines, and disease profiles. Compared to controls, SLE patients possessed a unique bladder microbial community and elevated alpha diversity. These differences were accompanied by differences in bladder metabolomes, cytokines, and patients' disease profiles. SLE-enriched genera were positively correlated with several SLE-enriched metabolites. SLE-depleted genera were negatively correlated to SLE-depleted cytokines. Alteration of the bladder microbiome was associated with disease profile. Thus, our study reveals associations between the bladder microbiome and the bladder metabolome, cytokines, and disease phenotypes. These results could help identify biomarkers for SLE.