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Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], −1.04[−1.19, −0.89]%) and BBR-alone group (−0.99[−1.16, −0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (−0.59[−0.75, −0.44]%, −0.53[−0.68, −0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii . Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261). The gut microbiome affects systemic metabolism and is a therapeutic target for type 2 diabetes. Here the authors demonstrate in a randomized controlled trial that effects of berberine, a plant alkaloid known to lower blood glucose, may be explained by the inhibition of Ruminococcus bromii mediated biotransformation of the bile acid deoxycholic acid.

The energy industry, acutely sensitive to geopolitical shifts due to the Russia-Ukraine conflict, experiences sustained disturbances in global energy markets, reshaping global energy supply dynamics and significantly influencing global trade patterns. Utilizing static and dynamic GARCH-Copula models, this study elucidates the dependency between energy markets and related assets. The Copula function, when compared with the multivariate GARCH model, demonstrates distinct advantages, notably in delineating joint asset distributions, capturing market dependence's nonlinear traits, and highlighting robust tail correlation structures. Beyond the average inter-market dependence, its tail correlation offers a vital perspective on market risk. This research delves into the temporal and structural variations in interdependence between energy markets and related assets. It probes potential structural breakpoints in dynamic interdependence and pinpoints their occurrences. By focusing on the Russia-Ukraine conflict, this study offers a holistic view of the changing interplay between the energy market and other asset categories, providing pivotal insights for investor portfolio optimization, regulatory oversight, and risk mitigation. Moreover, employing wavelet analysis, this study examines the frequency domain traits of the interdependency between energy markets and associated assets. As frequency wanes, market price fluctuations become less pronounced. The continuous wavelet power spectrum indicates that price variations are predominantly mid to high frequency. Cross-wavelet transform results suggest that correlations between energy markets and related assets are more influenced by short-term perturbations than enduring shifts.

Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs), possess immunomodulatory properties and have shown promising outcomes when combined with anti-PD-1 antibodies. The OASIS phase II trial (NCT04503967) is designed to determine the clinical activity and safety of nivolumab (anti-PD-1) and anlotinib hydrochloride (a multi-targets TKI) as second-line or above therapy in patients with advanced gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC). From December 2020 to September 2022, 45 patients with GAC and 3 with ESCC were enrolled in this study. The pre-specified endpoints were reached, with the primary endpoint of overall response rate achieving 29.2%. For secondary objectives, disease control rate was 64.6%; median progression-free survival was 4.0 months; and median overall survival was 11.1 months with a manageable toxicity profile. The exploratory analyses unveiled that the balance of gut bacteria and the presence of a pre-existing immune signature characterized by a high percentage of CD68 + PD-L1 + PD-1 + macrophages and low pretreatment variant allele frequencies (VAF), as well as low expression of certain cytokines were significantly associated with improved clinical outcomes in patients with GAC. Anlotinib hydrochloride is a multi-target tyrosine kinase receptor inhibitor, previously combined with anti-PD1 as therapeutic strategy for several cancer types. Here the authors report the results of a phase II trial of nivolumab (anti-PD1) plus anlotinib hydrochloride in patients with advanced gastric adenocarcinoma and esophageal squamous cell carcinoma.

Background The gut microbiota evolves from birth and is in early life influenced by events such as birth mode, type of infant feeding, and maternal and infant antibiotics use. However, we still have a gap in our understanding of gut microbiota development in older children, and to what extent early events and pre-school lifestyle modulate the composition of the gut microbiota, and how this impinges on whole body metabolic regulation in school-age children. Results Taking advantage of the KOALA Birth Cohort Study, a long-term prospective birth cohort in the Netherlands with extensive collection of high-quality host metadata, we applied shotgun metagenomics sequencing and systematically investigated the gut microbiota of children at 6–9 years of age. We demonstrated an overall adult-like gut microbiota in the 281 Dutch school-age children and identified 3 enterotypes dominated by the genera Bacteroides , Prevotella , and Bifidobacterium , respectively. Importantly, we found that breastfeeding duration in early life and pre-school dietary lifestyle correlated with the composition and functional competences of the gut microbiota in the children at school age. The correlations between pre-school dietary lifestyle and metabolic phenotypes exhibited a striking enterotype dependency. Thus, an inverse correlation between high dietary fiber consumption and low plasma insulin levels was only observed in individuals with the Bacteroides and Prevotella enterotypes, but not in Bifidobacterium enterotype individuals in whom the gut microbiota displayed overall lower microbial gene richness, alpha-diversity, functional potential for complex carbohydrate fermentation, and butyrate and succinate production. High total fat consumption and elevated plasma free fatty acid levels in the Bifidobacterium enterotype are associated with the co-occurrence of Streptococcus . Conclusions Our work highlights the persistent effects of breastfeeding duration and pre-school dietary lifestyle in affecting the gut microbiota in school-age children and reveals distinct compositional and functional potential in children according to enterotypes. The findings underscore enterotype-specific links between the host metabolic phenotypes and dietary patterns, emphasizing the importance of microbiome-based stratification when investigating metabolic responses to diets. Future diet intervention studies are clearly warranted to examine gut microbe-diet-host relationships to promote knowledge-based recommendations in relation to improving metabolic health in children.

To deepen the understanding of tissue-resident microbiota in colorectal cancer (CRC), we analyzed whole-genome and transcriptome data from 937 patients. We identified 249 genera and 361 species commonly present in both tumors and adjacent normal tissues (NATs). Distinct microbial signatures were associated with anatomical location, tumor stages, hypermutation status, mutations in CRC driver and DNA damage repair genes, as well as consensus molecular subtypes (CMSs). Notably, the presence of the pks island and elevated abundance of Enterobacteriaceae were linked to poor prognosis specifically in CMS2 tumors. Finally, microbial risk scores derived from taxa present in tumor or NATs predicted patient prognosis independently of established clinico-molecular factors. Prognostic taxa were strongly associated with tumor transcriptomic pathways related to hypoxia, immune response, and metabolic status. These findings revealed the heterogeneity of tissue-resident microbiota and their critical role in CRC progression, highlighting potential avenues for targeted intervention. Here, the authors show that colorectal tumors harbor diverse tissue-resident microbes whose compositions vary by tumor location and host genomics, and identify specific microbial signatures that predict patient prognosis beyond established clinical factors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Between 27 January and 26 February 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients in Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. We identified distinct signatures of microbial dysbiosis among severely ill COVID-19 patients on broad spectrum antimicrobial therapy. Co-detection of other human respiratory viruses (including human alphaherpesvirus 1, rhinovirus B, and human orthopneumovirus) was demonstrated in 30.8% (4/13) of the severely ill patients, but not in any of the mildly affected patients. Notably, the predominant respiratory microbial taxa of severely ill patients were Burkholderia cepacia complex (BCC), Staphylococcus epidermidis, or Mycoplasma spp. (including M. hominis and M. orale). The presence of the former two bacterial taxa was also confirmed by clinical cultures of respiratory specimens (expectorated sputum or nasal secretions) in 23.1% (3/13) of the severe cases. Finally, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes was demonstrated in one severely ill patient, which might accelerate his disease deterioration and death occurring one month after ICU admission. Our findings point to SARS-CoV-2-related microbial dysbiosis and various antibiotic-resistant respiratory microbes/pathogens in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking strategies are needed to prevent the spread of antimicrobial resistance, improve the treatment regimen and clinical outcomes of hospitalized, severely ill COVID-19 patients.

Background A comprehensive and representative reference database is crucial for accurate taxonomic and functional profiling of the human gut microbiome in population-level studies. However, as approximately 70% of current microbial reference data originate from European and North American populations, other regions, including East Asia—and particularly China—remain significantly underrepresented. Methods We constructed the human Gut Microbiome Reference (GMR), comprising 478,588 high-quality microbial genomes from Chinese (247,134) and non-Chinese (231,454) populations. Species-level clustering and protein annotations were performed to characterize microbial diversity and function. We further integrated novel microbial genomes into taxonomic profile database and validated the improvements using independent cohort data. Results The GMR dataset spans 6664 species, including 26.4% newly classified species, and encodes over 20 million unique proteins, with 47% lacking known functional annotations. Notably, we observed that 35.35 and 32.46% of species unique to Chinese and non-Chinese populations, respectively. For 2145 species shared between populations, 74% of 304 species with balanced prevalence between populations exhibited population-specific phylogenetic stratification, involving health relevant functionalities such as antibiotic resistance. Integration of novel genomes into taxonomic improved population-level species profiling by up to 23% and uncovered replicable associations between novel species and host physiological traits. Conclusions Our study largely expands the compositional and functional landscape of the human gut microbiome, providing a crucial resource for studying the role of gut microbiome for regional health disparities.

A prognostic biomarker that can provide a good prediction of prognosis in patients with intracerebral hemorrhage (ICH) would be beneficial in guiding the initial management decisions in the setting of ICH. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker of prognosis in patients with cardiovascular disease and ischemic stroke. However, the prognostic role of NT-proBNP in patients with spontaneous ICH is still a controversial issue. This study aimed to determine the prognostic value of NT-proBNP in patients with spontaneous ICH. A total of 132 patients from 571 ICH cases in inpatient settings were enrolled in this study. Blood samples from each subject were obtained and analyzed for NT-proBNP on admission and on days 4 and 7. The first end point was functional outcome at discharge, which was dichotomized into favorable or unfavorable; the secondary end point was mortality within 6 months after ICH. Compared with the baseline levels on admission after ICH, the NT-proBNP levels increased markedly on day 4 ( P  < 0.05). Multivariate logistic regression analysis indicated that the NT-proBNP level on day 4, the ICH score, and the APACHE II score were independent prognostic factors of functional outcome and 6-month mortality in ICH patients. A cutoff NT-proBNP level of 999.85 pg/ml predicted an unfavorable functional outcome (with 66.1% sensitivity and 98.7% specificity) and 6-month mortality (with 93.8% sensitivity and 92.0% specificity) in ICH patients. Thus, the NT-proBNP level on day 4 was found to be a powerful prognostic predictor of functional outcome and 6-month mortality in ICH patients, which would be beneficial to guiding the initial management decisions in the setting of ICH.

Background Bladder cancer is a common malignancy of the genitourinary system. Recent studies have confirmed the existence of microorganisms in urine. This study aimed to characterize changes in the urinary microbiota of Chinese bladder cancer patients and determine differences between patients with muscle‐invasive bladder cancer (MIBC) and those with non‐muscle‐invasive bladder cancer (NMIBC). Methods Urine samples were collected from 64 patients with bladder cancer and 94 disease‐free controls using the clean catch method and sequenced by 16S rRNA gene sequencing. Sequencing reads were filtered by VSEARCH and clustered by UPARSE. Results Significant associations were found between urinary microbiota and factors such as sex, age, and disease status. After age adjustment, differences in beta diversity were observed between healthy men and women, cancer patients and healthy controls, and NMIBC and MIBC patients. The cancer patients had an increased abundance of 14 bacterial genera, including Stenotrophomonas, Propionibacterium, and Acinetobacter. Notably, Peptoniphilus spp. were enriched in high‐risk MIBC patients, indicating their potential as a risk marker. Functional prediction via PICRUSt analysis suggested enriched metabolic pathways in specific disease groups. Furthermore, molecular ecological network analysis revealed differences based on sex and disease type. Conclusions This significant microbial diversity indicates a potential correlation between urinary microbiota dysbiosis and bladder cancer, with implications for risk stratification and disease management. The identified urinary microbiota may serve as noninvasive markers for bladder cancer, warranting further validation in larger cohorts. This study provides a foundation for further research on the mechanisms of bladder cancer progression. Urinary microbiota in Chinese bladder cancer patients reveals distinct profiles between non‐muscle‐invasive and muscle‐invasive diseases, with potential biomarkers like Peptoniphilus spp. in high‐risk MIBC, suggesting a role in cancer progression. Dysbiosis may serve as a stratification marker for bladder cancer risk.