The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.

https://www.nejm.org/doi/pdf/10.1056/NEJMra1600266

The Human Intestinal Microbiome in Health and Disease

Observational findings achieved during the past two decades suggest that the intestinal microbiota may contribute to the metabolic health of the human host and, when aberrant, to the pathogenesis of various common metabolic disorders including obesity, type 2 diabetes, non-alcoholic liver disease, cardio-metabolic diseases and malnutrition. However, to gain a mechanistic understanding of how the gut microbiota affects host metabolism, research is moving from descriptive microbiota census analyses to cause-and-effect studies. Joint analyses of high-throughput human multi-omics data, including metagenomics and metabolomics data, together with measures of host physiology and mechanistic experiments in humans, animals and cells hold potential as initial steps in the identification of potential molecular mechanisms behind reported associations. In this Review, we discuss the current knowledge on how gut microbiota and derived microbial compounds may link to metabolism of the healthy host or to the pathogenesis of common metabolic diseases. We highlight examples of microbiota-targeted interventions aiming to optimize metabolic health, and we provide perspectives for future basic and translational investigations within the nascent and promising research field. In this Review, Fan and Pedersen discuss how the gut microbiota and derived microbial compounds may contribute to human metabolic health and to the pathogenesis of common metabolic diseases, and highlight examples of microbiota-targeted interventions aiming to optimize metabolic health.

Gut microbiota in human metabolic health and disease.

Background: Understanding of the gut-liver axis is important for the up-to-date management of liver cirrhosis, and changes of intestinal functions form the core o

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Changes of Intestinal Functions in Liver Cirrhosis

Diverse microbial communities of bacteria, archaea, viruses and single-celled eukaryotes have crucial roles in the environment and in human health. However, microbes are frequently difficult to culture in the laboratory, which can confound cataloging of members and understanding of how communities function. High-throughput sequencing technologies and a suite of computational pipelines have been combined into shotgun metagenomics methods that have transformed microbiology. Still, computational approaches to overcome the challenges that affect both assembly-based and mapping-based metagenomic profiling, particularly of high-complexity samples or environments containing organisms with limited similarity to sequenced genomes, are needed. Understanding the functions and characterizing specific strains of these communities offers biotechnological promise in therapeutic discovery and innovative ways to synthesize products using microbial factories and can pinpoint the contributions of microorganisms to planetary, animal and human health.

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Shotgun metagenomics, from sampling to analysis

Recently, the potential role of gut microbiome in metabolic diseases has been revealed, especially in cardiovascular diseases. Hypertension is one of the most prevalent cardiovascular diseases worldwide, yet whether gut microbiota dysbiosis participates in the development of hypertension remains largely unknown. To investigate this issue, we carried out comprehensive metagenomic and metabolomic analyses in a cohort of 41 healthy controls, 56 subjects with pre-hypertension, 99 individuals with primary hypertension, and performed fecal microbiota transplantation from patients to germ-free mice. Compared to the healthy controls, we found dramatically decreased microbial richness and diversity, Prevotella-dominated gut enterotype, distinct metagenomic composition with reduced bacteria associated with healthy status and overgrowth of bacteria such as Prevotella and Klebsiella, and disease-linked microbial function in both pre-hypertensive and hypertensive populations. Unexpectedly, the microbiome characteristic in pre-hypertension group was quite similar to that in hypertension. The metabolism changes of host with pre-hypertension or hypertension were identified to be closely linked to gut microbiome dysbiosis. And a disease classifier based on microbiota and metabolites was constructed to discriminate pre-hypertensive and hypertensive individuals from controls accurately. Furthermore, by fecal transplantation from hypertensive human donors to germ-free mice, elevated blood pressure was observed to be transferrable through microbiota, and the direct influence of gut microbiota on blood pressure of the host was demonstrated. Overall, our results describe a novel causal role of aberrant gut microbiota in contributing to the pathogenesis of hypertension. And the significance of early intervention for pre-hypertension was emphasized.

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Gut microbiota dysbiosis contributes to the development of hypertension.

Background Cellular senescence is a key element in the occurrence and progression of a variety of tumors. As a result, cellular senescence-related markers can be categorized based on the prognosis status of patients. Due to the heterogeneity and the complexity of the tumor microenvironment (TME), the long-term effectiveness of low-grade glioma (LGG) treatment remains a clinical challenge. Consequently, developing and refining effective treatment approaches to aid with LGG management is critical. Methods Based on the expressions of cell senescence-related genes (CSRGs) acquired from the cellAge database, consensus clustering was utilized to identify stable molecular subtypes. Clinical features, immune infiltration, route modifications, and genetic changes of various subtypes were also assessed. Following that, the least absolute shrinkage and selection operator (LASSO) regression and univariate Cox regression analysis were used for developing the cell senescence-related risk score (CSRS) model. Finally, a correlation study of the CSRS model with molecular, immunological, and immunotherapy parameters was performed. Results C1, C2, and C3, are the three senescence-related subtypes that were identified. Patients belonging to the C1 subtype had poor prognoses and a substantial proportion of them was in the grade G3. The differentially expressed genes (DEGs) among the three subtypes were used to develop the CSRS model. In both the training and independent validation cohort, the model had a high area under the receiver operating characteristic (ROC) curve in predicting the overall survival (OS) of patients. As a result, this model can predict clinical features and responses to immunotherapy in a variety of patients and it is a potential independent prognostic factor for LGG. Conclusion This research discovered three LGG subtypes related to cell senescence and created a CSRS model for six genes. Cell senescence was highly associated with unfavorable prognosis in LGG. The CSRS model can be used to predict the prognosis of patients and identify patients who would benefit from immunotherapy.

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Establishment of three heterogeneous subtypes and a risk model of low-grade gliomas based on cell senescence-related genes

The invention discloses a kit for detecting drug resistance genes of ten trimethoprim drugs. The kit comprises an amplification primer combination for carrying out specific amplification on the drug resistance genes of the ten trimethoprim drugs and a specific probe for detecting on the drug resistance genes of the ten trimethoprim drugs. The invention further discloses a method for detecting thedrug resistance genes of the ten trimethoprim drugs by using the kit. The method for detecting the drug resistance genes of the trimethoprim drugs and the kit thereof have the characteristics of highintegration degree, high sensitivity, good specificity, stable and reliable detection results and low cost, can be widely used for distribution and epidemiological monitoring of the drug resistance genes of the trimethoprim drugs, and provides an effective tool for rational drug use and effective reduction and delay of drug resistance.

Method and kit for detecting drug resistance genes of ten trimethoprim drugs

The invention discloses a kit for detecting drug resistance genes of 20 dfrA methoxy benzylamine pyrimidine drugs. The kit comprises a amplification primer combination for specifically amplifying drugresistance genes of 20 dfrA methoxy benzylamine pyrimidine drugs and also comprises specific probes for detecting drug resistance genes of 20 dfrA methoxy benzylamine pyrimidine drugs. The inventionalso provides a method of detecting drug resistance genes of 20 dfrA methoxy benzylamine pyrimidine drugs by employing the kit. Various drug resistance genes are detected at the same time in a PCR amplification reaction at one time, and a step of being hybrized with the specific probes, so that the specificity of detection is improved greatly. The method and kit are convenient and rapid, and the detection cost is also lowered greatly.

Method of detecting drug resistance genes of 20 dfrA methoxy benzylamine pyrimidine drugs and kit used

The invention discloses a specific primer and probe combination for detecting four types of drug-resistant genes of glycopeptide drugs in gram positive bacteria. The combination comprises a primer combination for performing specific amplification on the four types of drug-resistant genes of the glycopeptide drugs, and also comprises a specific probe for detecting the four types of drug-resistant genes of the glycopeptide drugs. Meanwhile, the invention discloses a method for detecting the four types of drug-resistant genes of the glycopeptide drugs by using the specific primer and probe combination. The specific primer and probe combination has the advantages of high specificity and coverage degree, can be used for the high-specificity, high-sensitivity, fast and synchronous detection on the drug-resistant genes of vanF, vanI, vanJ and vanO of environment samples of soil, water bodies and the like, particularly in farm places of livestock, poultry, aquatic products and the like; the distribution and transfer conditions of relevant drug-resistant genes are monitored; the specific primer and probe combination can also be used for detecting the drug-resistant genes of vanF, vanI, vanJand vanO in animal or human body infection samples.

Specific primer and probe combination for detecting four types of drug-resistant genes of glycopeptide drugs in gram positive bacteria and application

ABSTRACT Emerging mobile colistin resistance (mcr) genes pose a significant threat to public health for colistin was used as the last resort to treat multidrug-resistant (MDR) pathogenic bacterial infections. Hypervirulent Klebsiella pneumoniae (hvKP) is a clinically significant pathogen resulting in highly invasive infections, often complicated by devastating dissemination. Worryingly, the untreatable and severe infections caused by mcr-harbouring hvKP leave the selection of antibiotics for clinical anti-infective treatment in a dilemma. Herein, we screened 3,461 isolates from a tertiary teaching hospital from November 2018 to March 2021, and an mcr-8.2-harbouring hvKP FAHZZU2591 with a conjugative plasmid was identified from paediatric sepsis. This is the first report of MCR-8-producing hvKP from paediatric sepsis to our best knowledge. The susceptibility, genetic features, and plasmid profiles of the isolate were investigated. Further, we assessed the virulence potential of FAHZZU2591 and verified its pathogenicity and invasive capacity using a mouse model. The phylogenetic analysis of mcr-8-bearing K. pneumoniae revealed that China is the predominant reservoir of the mcr-8 gene, and the clinic is the primary source. Our work highlights the risk for the spread of mcr-positive hvKP in clinical, especially in paediatric sepsis, and the persistent surveillance of colistin-resistance hvKP is urgent.

Lingjiao Wu

Papers

Establishment of three heterogeneous subtypes and a risk model of low-grade gliomas based on cell senescence-related genes

Method and kit for detecting drug resistance genes of ten trimethoprim drugs

Method of detecting drug resistance genes of 20 dfrA methoxy benzylamine pyrimidine drugs and kit used

Specific primer and probe combination for detecting four types of drug-resistant genes of glycopeptide drugs in gram positive bacteria and application

Emergence of mcr-8.2-harboring hypervirulent ST412 Klebsiella pneumoniae strain from pediatric sepsis: A comparative genomic survey