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Introduction: Melophagus ovinus , a parasite on the body surface of sheep, directly attacks the host through biting and sucking blood and may also transmit pathogens in the process. There are currently only a few studies on the microbial composition of M. ovinus , while there are no such studies on pupae. Methods: In this study, samples AT-1 to AT-4 each contained four M. ovinus individuals, while sample AT-5 comprised four M. ovinus pupae, all used for metagenomic sequencing and analysis. Melophagus ovinus adults and pupae were collected from four regions in Xinjiang, China. DNA was extracted from the samples, amplified, and sequenced using the Illumina Novaseq 6000 System; finally, the sequencing data were analyzed using molecular biology software. Results and discussion: From all samples, a total of 32 phyla, comprising 372 genera and 1,037 species, were detected. The highest microbial diversity was observed in Kuqa City (AT-2) and Qira County (AT-4). Pupae exhibited 40 unique microbial genera (AT-5) but did not have the highest microbial diversity. Proteobacteria was the dominant phylum in all samples. The dominant genera included Bartonella , Wolbachia , Pseudomonas , and Arsenophonus. This is the first study to report most of the bacteria (e.g., Pseudomonas versuta and Arsenophonus nasoniae), fungi (e.g., Saitoella complicata), viruses (e.g., Orf virus and Wolbachia phage WO), and protozoa (e.g., Trypanosoma theileri and Babesia bigemina) in M. ovinus. This study has enriched the microbial diversity data of M. ovinus , and the pathogens it carries may pose a threat to public health safety and the economy of related industries, necessitating further research to develop effective biological control strategies. [ABSTRACT FROM AUTHOR]

IntroductionMelophagus ovinus, a parasite on the body surface of sheep, directly attacks the host through biting and sucking blood and may also transmit pathogens in the process. There are currently only a few studies on the microbial composition of M. ovinus, while there are no such studies on pupae.MethodsIn this study, samples AT-1 to AT-4 each contained four M. ovinus individuals, while sample AT-5 comprised four M. ovinus pupae, all used for metagenomic sequencing and analysis. Melophagus ovinus adults and pupae were collected from four regions in Xinjiang, China. DNA was extracted from the samples, amplified, and sequenced using the Illumina Novaseq 6000 System; finally, the sequencing data were analyzed using molecular biology software.Results and discussionFrom all samples, a total of 32 phyla, comprising 372 genera and 1,037 species, were detected. The highest microbial diversity was observed in Kuqa City (AT-2) and Qira County (AT-4). Pupae exhibited 40 unique microbial genera (AT-5) but did not have the highest microbial diversity. Proteobacteria was the dominant phylum in all samples. The dominant genera included Bartonella, Wolbachia, Pseudomonas, and Arsenophonus. This is the first study to report most of the bacteria (e.g., Pseudomonas versuta and Arsenophonus nasoniae), fungi (e.g., Saitoella complicata), viruses (e.g., Orf virus and Wolbachia phage WO), and protozoa (e.g., Trypanosoma theileri and Babesia bigemina) in M. ovinus. This study has enriched the microbial diversity data of M. ovinus, and the pathogens it carries may pose a threat to public health safety and the economy of related industries, necessitating further research to develop effective biological control strategies.

Metagenomic sequencing has emerged as a transformative tool in infectious disease diagnosis, offering a comprehensive and unbiased approach to pathogen detection. Leveraging international standards and guidelines is essential for ensuring the quality and reliability of metagenomic sequencing in clinical practice. This review explores the implications of international standards and guidelines for the application of metagenomic sequencing in infectious disease diagnosis. By adhering to established standards, such as those outlined by regulatory bodies and expert consensus, healthcare providers can enhance the accuracy and clinical utility of metagenomic sequencing. The integration of international standards and guidelines into metagenomic sequencing workflows can streamline diagnostic processes, improve pathogen identification, and optimize patient care. Strategies in implementing these standards for infectious disease diagnosis using metagenomic sequencing are discussed, highlighting the importance of standardized approaches in advancing precision infectious disease diagnosis initiatives. [ABSTRACT FROM AUTHOR]

The Dong Taijinar (DT) and Xi Taijinar (XT) Salt Lakes have been extensively researched for their mineral richness. However, the composition and distribution of their microbial communities are still poorly known. In this study, we employed metagenomic sequencing to explore the diversity and potential functions of the microbial populations in DT and XT. Our findings indicate that the salinity levels in DT (332.18–358.30 g/L) were tenfold higher than in XT (20.09–36.83 g/L). Notably, archaea dominated the DT domain at 96.16%, while bacteria prevailed in XT at 93.09%. In DT, the bacterial community comprised 33 phyla and 1717 genera, with Marinobacter emerging as the dominant genus, showing a positive correlation with the total phosphorus content. The archaeal community in DT included four main phyla and 153 genera. The most abundant genera were Natronomonas (24.61%) and Halorubrum (23.69%), which had a strong positive correlation with the concentrations of Na+, Ca2+, and Cl−. Conversely, XT hosted 33 phyla and 1906 bacterial genera, with Loktanella as the dominant genus. The archaeal taxonomy in XT encompassed four phyla and 149 genera. In both salt lakes, Proteobacteria and Euryarchaeota were the most abundant bacterial and archaeal phyla, respectively. Our analysis of the halophilic mechanisms of these microorganisms suggests that the bacteria in XT tend to synthesize compatible solutes, whereas the archaea in DT adopt a 'salt-in' strategy, integrating salt into their cellular machinery to cope with the high-salinity environment. [ABSTRACT FROM AUTHOR]

Vermifiltration (VF) and a conventional biofilter (BF, no earthworm) were investigated by metagenomics to evaluate the removal rates of antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs), and class 1 integron-integrase (intI1), as well as the impact mechanism in combination with the microbial community. According to the findings of qPCR and metagenomics, the VF facilitated greater removal rates of ARGs (78.83% ± 17.37%) and ARB (48.23% ± 2.69%) than the BF (56.33% ± 14.93%, 20.21% ± 6.27%). Compared to the control, the higher biological activity of the VF induced an increase of over 60% in the inhibitory effect of earthworm coelomic fluid on ARB. The removal rates of ARGs by earthworm guts also reached over 22%. In addition, earthworms enhanced the decomposition of refractory organics, toxic, and harmful organics, which led to a lower selective pressure on ARGs and ARB. It provides a strategy for reducing resistant pollution in sewage treatment plants and recognizing the harmless stability of sludge. [ABSTRACT FROM AUTHOR]

BACKGROUND: The rice moth, Corcyra cephalonica (Stainton) (Lepidoptera: Pyralidae) is a pest of stored grains and widely used as a factitious host during the mass rearing of several natural enemies of crop pests. Hormesis is well‐documented in pest insects, to some extent in natural enemies of pests. RESULTS: We report transgenerational stimulatory effects of the widely used fumigant, phosphine. The study reports the consequences of sublethal, low lethal and median lethal concentrations (LC5, LC25 and LC50) and untreated control for two sequential generations of the species (G1 to G2). In this study, we investigated the life‐history traits, nutrient reserves (protein, lipid and carbohydrate) and larval gut microbiome (using 16 s rRNA V3–V4 metagenomics sequencing) of C. cephalonica. Stimulatory effects were observed for various biological traits of C. cephalonica, notably adult longevity, emergence and increased egg hatchability when exposed to LC5 of phosphine. The total protein, lipid and carbohydrate contents of C. cephalonica also were found to be significantly increased by LC5 in both generations. The microbial diversity of LC5 treated larval gut was higher and found to be different from the rest of the treatments. This is the first report showing hormesis to a fumigant insecticide. CONCLUSION: Our findings increase knowledge on the interaction between hormesis, nutrient reserves and gut bacteria in C. cephalonica exposed to insecticides. Overall, the present study establishes phosphine‐induced hormesis at LC5 in the host C. cephalonica, which might help improve the quality of mass rearing of various natural enemies. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Aichi virus C , a species in the genus Kobuvirus , causes diarrhea diseases in pigs and goats and pose health threat and economic loss for stock farming. A nearly complete genome sequence of caprine kobuvirus GCCDC14 was obtained from an anal swab of a black goat died from diarrhea collected in Hubei, China in 2019. Phylogenetic analyses suggested that GCCDC14 is a novel genotype of Aichi virus C, forming a sister branch to other caprine kobuviruses, with P1 and VP0 genes more closely related to porcine kobuviruses and VP3 in an independent branch. Compared to previous caprine kobuviruses, unique amino acid changes in the poly- l -proline type II helix structure of VP0 and VP1 were found, which may affect the cellular machinery of host and pathogenicity. This study indicates the presence of the kobuvirus with continuously evolving features and emphasizes the surveillance and genetic evolution investigation of kobuviruses for safety of husbandry. [Display omitted] • First detection of caprine kobuvirus in black goats in central China. • This caprine kobuvirus had varying degrees of amino acid mutations in the poly- l -proline type Ⅱ helix structural region of VP0 and VP1. • Homology comparsion and phylogenetic trees showed that the caprine kobuvirus was probably a novel genotype of Aichi virus C , forming a separate cluster within it. [ABSTRACT FROM AUTHOR]

The top-gray chalkiness of hybrid rice (Oryza sativa L.) seeds is a typical phenomenon in hybrid rice seeds. The chalky part of the grain is infected and is the inoculum to infect the normal seeds during storage and soaking. These seed-associated microorganisms were cultivated and sequenced using metagenomics shotgun sequencing to obtain more comprehensive information on the seed-associated microorganisms in this experiment. The results showed that fungi could grow well on the rice flour medium, similar to the ingredients of rice seed endosperms. After the assembly of metagenomic data, a gene catalog was established, comprising 250,918 genes. Function analysis showed that glycoside hydrolases were the dominant enzymes, and the genus Rhizopus accounted for the dominant microorganisms. The fungal species R. microspores, R. delemar, and R. oryzae were likely to be the candidate pathogens in the top-gray chalky grains of hybrid rice seeds. These results will provide a reference for improving hybrid rice processing after harvest. [ABSTRACT FROM AUTHOR]

The microbiome is of great interest due to its potential influence on the occurrence and treatment of some human illnesses. It may be regarded as disruptions to the delicate equilibrium that humans ordinarily maintain with their microorganisms or the microbiota in their environment. The focus of this review is on the methodologies and current understanding of the functional microbiome in pregnancy outcomes. We present how novel techniques bring new insights to the contemporary field of maternal–fetal medicine with a critical analysis. The maternal microbiome in late pregnancy has been extensively studied, although data on maternal microbial changes during the first trimester are rare. Research has demonstrated that, in healthy pregnancies, the origin of the placental microbiota is oral (gut) rather than vaginal. Implantation, placental development, and maternal adaptation to pregnancy are complex processes in which fetal and maternal cells interact. Microbiome dysbiosis or microbial metabolites are rising as potential moderators of antenatal illnesses related to the placenta, such as fetal growth restriction, preeclampsia, and others, including gestational diabetes and preterm deliveries. However, because of the presence of antimicrobial components, it is likely that the bacteria identified in placental tissue are (fragments of) bacteria that have been destroyed by the placenta's immune cells. Using genomic techniques (metagenomics, metatranscriptomics, and metaproteomics), it may be possible to predict some properties of a microorganism's genome and the biochemical (epigenetic DNA modification) and physical components of the placenta as its environment. Despite the results described in this review, this subject needs further research on some major and crucial aspects. The phases of an in utero translocation of the maternal gut microbiota to the fetus should be explored. With a predictive knowledge of the impacts of the disturbance on microbial communities that influence human health and the environment, genomics may hold the answer to the development of novel therapies for the health of pregnant women. [ABSTRACT FROM AUTHOR]

Introduction: Long-chain fatty acids in breast milk are affected by the mother's diet and play an important role in the growth, development, and immune construction of infants. This study aims to explore the correlation between maternal diet, breast milk fatty acids (FAs), and the infant intestinal flora. Methods: We enrolled 56 paired mothers and their infants; both breast milk samples and infants' fecal samples were collected to determine the longchain FA content of breast milk by ultra-performance liquid chromatography-- tandem mass spectrometry (UPLC-MS), and metagenomic technology was applied to determine the microbial composition of infant feces. The maternal diet was also investigated using a 24-h dietary recall. Results: The results indicated that the fat contribution rates of edible oils in the maternal diet are significantly positively correlated with the contents of certain long-chain fatty acids (C16:0, C18:1, C16:1, and C22:4) in breast milk, which mainly regulate the abundance of Lacticaseibacillus rhamnosus, Lacticaseibacillus fermentum, and Lacticaseibacillus paracasei in the infant gut. Through KEGG pathway analysis, our data revealed that the long-chain FAs in different groups of breast milk were significantly correlated with the pathways of biotin metabolism, glycerolipid metabolism, and starch and sucrose metabolism. Discussion: The results of this study suggest a pathway in which the diets of lactating mothers may affect the composition of the infant intestinal microbiota by influencing breast milk FAs and then further regulating infant health. [ABSTRACT FROM AUTHOR]

Most zoonotic pathogens originate from mammals and avians, but viral diversity and related biosafety risk assessment in lower vertebrates also need to be explored. Amphibians are an important group of lower vertebrates that played a momentous role in animal evolution. To elucidate the diversity of RNA viruses in one important species of amphibians, the Asiatic toad (Bufo gargarizans), we obtained 44 samples including lung, gut, liver, and kidney tissues from Asiatic toads in Sichuan and Jilin provinces, China, for viral metagenomics sequencing. More than 20 novel RNA viruses derived from the order Bunyavirales and 7 families of Astroviridae, Dicistroviridae, Leviviridae, Partitiviridae, Picornaviridae, Rhabdoviridae, and Virgaviridae were discovered, which were distinct from previously described viruses and formed new clusters, as revealed by phylogenetic analyses. Notably, a novel bastrovirus, AtBastV/GCCDC11/2022, of the family Astroviridae was identified from the gut library, the genome of which contains three open reading frames, with the RNA-dependent RNA polymerase (RdRp) coded by ORF1 closely related to that of hepeviruses, and ORF2 encoding an astrovirus-related capsid protein. Notably, phenuiviruses were discovered for the first time in amphibians. AtPhenV1/GCCDC12/2022 and AtPhenV2/GCCDC13/2022 clustered together and formed a clade with the group of phenuiviruses identified from rodents. Picornaviruses and several invertebrate RNA viruses were also detected. These findings improve our understanding of the high RNA viral diversity in the Asiatic toad and provide new insights in the evolution of RNA viruses in amphibians. [ABSTRACT FROM AUTHOR]

A brain abscess is a focal collection of pus in the brain parenchyma surrounded by a well-vascularized collagenous capsule in response to an infection. The microbiome of brain abscesses has been shown to be polymicrobial, dominated by uncultivable and anaerobic organisms of odontogenic origin. The data provided in this article includes the sequences of bacterial 16S rRNA gene from three culture-negative brain abscess samples suspected to have poly-microbial aetiology based on Sanger sequencing. DNA was extracted from brain abscess samples, and targeted-metagenomics sequencing was done by amplifying the full-length bacterial 16S rRNA followed by a nested PCR for V3-V4 regions using universal and specific primers. The barcoded amplicons were sequenced on Illumina MiSeq V2 instrument to generate 0.5M, 250bp paired-end reads/sample. The total sequencing reads were 455966, 345746, and 438658 for samples P32, P49, and P8, respectively. Bioinformatics tools such as FLASH, VSEARCH, and QIIME1 were used to process the reads generated for Operational Taxonomic Unit analysis (OTU). Bacterial species belonging to phyla Firmicutes, Bacteroidetes, and Fusobacteria were abundant in samples P49 and P8, which are mainly anaerobic and microaerophilic bacteria. These are typical of the human oral/gut microbiota and are implicated in brain abscess formation. Sample P32 showed the abundance of bacterial species belonging to phyla Proteobacteria and Actinobacteria, which are commonly found in the environment. Raw data files are available at the Sequence Read Archive (SRA), National Center for Biotechnology Information (NCBI), and data information can be found at the BioProject, PRJNA785100 under the accession numbers SRX13271109, SRX13271110, SRX13295897. The data shows the microbiome constitution, including several anaerobic and unculturable bacterial species from culture-negative brain abscess samples. This dataset will be useful for future research on comparative genomics and management of patients with culture-negative brain abscesses.

The widespread occurrence of clinically relevant antibiotic resistance within humans, animals, and environment motivates the development of sensitive and accurate detection and quantification methods. Metagenomics and quantitative PCR (qPCR) are amongst the most used approaches. In this study, we aimed to evaluate and compare the performance of these methods to screen antibiotic resistance genes in animal faecal, wastewater, and water samples. Water and wastewater samples were from hospital effluent, different treatment stages of two treatment plants, and of the receiving river at the discharge point. The animal samples were from pig and chicken faeces. Antibiotic resistance gene coverage, sensitivity, and usefulness of the quantitative information were analyzed and discussed. While both methods were able to distinguish the resistome profiles and detect gradient stepwise mixtures of pig and chicken faeces, qPCR presented higher sensitivity for the detection of a few antibiotic resistance genes in water/wastewater. In addition, the comparison of predicted and observed antibiotic resistance gene quantifications unveiled the higher accuracy of qPCR. Metagenomics analyses, while less sensitive, provided a markedly higher coverage of antibiotic resistance genes compared to qPCR. The complementarity of both methods and the importance of selecting the bestmethod according to the study purpose are discussed. [ABSTRACT FROM AUTHOR]

Metagenomic next-generation sequencing (mNGS) is increasingly being recognized as a valuable diagnostic tool for periprosthetic joint infections (PJIs). This study reviews the diagnostic utility of mNGS, highlighting its improved sensitivity in detecting pathogens, particularly in culture-negative and polymicrobial infections. However, the clinical application of this method is hindered by challenges such as the prevalence of host DNA, the necessity for extensive bioinformatic analysis, and the potential for contamination, which can lead to misinterpretation of results. As mNGS continues to evolve, it holds significant potential to improve the management of PJI and enhance the application of precision medicine in orthopedic infections., Competing Interests: Disclosure A.J. Tande reports honoraria from UpToDate not related to this article. There are no other financial disclosures or conflicts of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Frans Dany, Sela Septima Mariya, Ariyani Noviantari Center for Biomedical Research, Health Research Organization, National Research and Innovation Agency (BRIN), Cibinong, West Java, IndonesiaCorrespondence: Frans Dany, Biomedical Research Center, Health Research Organization, Genomic Building, Cibinong Science Center, Jl. Raya Bogor No. 490, Cibinong, 16911, West Java, Indonesia, Email fran012@brin.go.id; fransdany1@gmail.com

Abstract Background Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high. Trial registration ClinicalTrials.gov Identifier: NCT01538550 .

The top-gray chalkiness of hybrid rice (Oryza sativa L.) seeds is a typical phenomenon in hybrid rice seeds. The chalky part of the grain is infected and is the inoculum to infect the normal seeds during storage and soaking. These seed-associated microorganisms were cultivated and sequenced using metagenomics shotgun sequencing to obtain more comprehensive information on the seed-associated microorganisms in this experiment. The results showed that fungi could grow well on the rice flour medium, similar to the ingredients of rice seed endosperms. After the assembly of metagenomic data, a gene catalog was established, comprising 250,918 genes. Function analysis showed that glycoside hydrolases were the dominant enzymes, and the genus Rhizopus accounted for the dominant microorganisms. The fungal species R. microspores, R. delemar, and R. oryzae were likely to be the candidate pathogens in the top-gray chalky grains of hybrid rice seeds. These results will provide a reference for improving hybrid rice processing after harvest.

Nitrate-dependent anaerobic methane oxidation (Nitrate-DAMO) is a novel and sustainable process that removes both nitrogen and methane. Previously, the metabolic pathway of Nitrate-DAMO has been intensively studied with some results. However, the production and consumption of nitrous oxide (N 2 O) in the Nitrate-DAMO system were widely disregarded. In this study, a Nitrate-DAMO system was used to investigate the effect of operational parameters (C/N ratio, pH, and temperature) on N 2 O accumulation, and the optimal operating conditions were determined (C/N = 3, pH = 6.5, and temperature = 20 °C). In this study, an enzyme kinetic model was used to fit the nitrate nitrogen degradation and the nitrous oxide production and elimination under different operating conditions. The thermodynamic model of N 2 O production and elimination in the system also has been constructed. Multiple linear regression analysis found that pH was the most important factor influencing N 2 O accumulation. The Metagenomics sequencing results showed that alkaline pH promoted the abundance of Nor genes and denitrifying bacteria, which were significantly and positively correlated with N 2 O emissions. And alkaline pH also promoted the production of Mdo genes related to the N 2 O-driven AOM reaction, indicating that part of the N 2 O was consumed by denitrifying bacteria and the other part was consumed by the N 2 O-driven AOM reaction. These findings reveal the mechanism of N 2 O production and consumption in DAMO systems and provide a theoretical basis for reducing N 2 O production and greenhouse gas emissions in actual operation. [Display omitted] • The optimum operation conditions of the N-DAMO system were explored. • The enzyme kinetic model well fitted to the measured N 2 O production. • Alkaline increased the abundance of Nor genes, leading to N 2 O accumulation. • N 2 O reductase activity decreased with increasing pH. • The production and consumption pathways of N 2 O in the N-DAMO system were proposed. [ABSTRACT FROM AUTHOR]

Background: Liver cirrhosis is the common end-stage of liver disease which lacks effective treatment, thus studies to determine prevention targets are an urgent need. The intestinal microbiota (IM) play important roles in modulating liver diseases which are mediated by microbial metabolites. Despite decades of growing microbial studies, whether IM contribute to the development of cirrhosis and the intimate metabolic link remain obscure. Here, we aimed to reveal the dynamic alterations of microbial composition and metabolic signatures in carbon tetrachloride (CCl4)-induced liver cirrhosis mice.Methods: CCl4-treated mice or normal control (NC) were sacrificed (n = 10 per group) after 5 and 15 weeks of intervention. The disease severity was confirmed by Masson’s trichrome or Sirius red staining. Metagenomics sequencing and fecal untargeted metabolomics were performed to evaluate the composition and metabolic function of IM in parallel with the development of cirrhosis.Results: The CCl4-treated mice presented liver fibrosis at 5 weeks and liver cirrhosis at 15 weeks indicated by collagen deposition and pseudo-lobule formation, respectively. Mice with liver cirrhosis showed distinct microbial composition from NC, even in the earlier fibrosis stage. Importantly, both of the liver fibrosis and cirrhosis mice were characterized with the depletion of Deltaproteobacteria (p < 0.05) and enrichment of Akkermansia (p < 0.05). Furthermore, fecal metabolomics revealed distinguished metabolomics profiles of mice with liver fibrosis and cirrhosis from the NC. Notably, pathway enrichment analysis pointed to remarkable disturbance of purine (p < 0.001 at 5 weeks, p = 0.034 at 15 weeks) and pyrimidine metabolic pathways (p = 0.005 at 5 weeks, p = 0.006 at 15 weeks) during the development of liver cirrhosis. Interestingly, the disorders of pyrimidine and purine metabolites like the known microbial metabolites thymidine and 2′-deoxyuridine had already occurred in liver fibrosis and continued in cirrhosis.Conclusion: These novel findings indicated the crucial role of IM-modulated pyrimidine and purine metabolites in the development of liver cirrhosis, which provides microbial targets for disease prevention.

We previously demonstrated in non-human primates (NHP) that Mediterranean diet consumption shifted the proportional abundance of Lactobacillus in the breast and gut. This data highlights a potential link about gut-breast microbiome interconnectivity. To address this question, we compared bacterial populations identified in matched breast and faecal samples from our NHP study. Dietary pattern concurrently shifted two species in both regions; Streptococcus lutetiensis and Ruminococcus torques. While we observe similar trends in Lactobacillus abundances in the breast and gut, the species identified in each region vary; Mediterranean diet increased Lactobacillus_ unspecified species in breast but regulated L. animalis and L. reuteri in the gut. We also investigated the impact of gut permeability on the breast microbiome. Regardless of dietary pattern, subjects that displayed increased physiological measures of gut permeability (elevated plasma lipopolysaccharide, decreased villi length, and decreased goblet cells) displayed a significantly different breast microbiome. Gut barrier dysfunction was associated with increased α-diversity and significant different β-diversity in the breast tissue. Taken together our data supports the presence of a breast microbiome influenced by diet that largely varies from the gut microbiome population but is, however, sensitive to gut permeability.

Wepreviously demonstrated in non-human primates (NHP) thatMediterranean diet consumption shifted the proportional abundance of Lactobacillus in the breast and gut. This data highlights a potential link about gutbreast microbiome interconnectivity. To address this question, we compared bacterial populations identified in matched breast and faecal samples fromourNHP study. Dietary pattern concurrently shifted two species in both regions; Streptococcus lutetiensis and Ruminococcus torques. While we observe similar trends in Lactobacillus abundances in the breast and gut, the species identified in each region vary; Mediterranean diet increased Lactobacillus_ unspecified species in breast but regulated L. animalis and L. reuteri in the gut. We also investigated the impact of gut permeability on the breast microbiome. Regardless of dietary pattern, subjects that displayed increased physiological measures of gut permeability (elevated plasma lipopolysaccharide, decreased villi length, and decreased goblet cells) displayed a significantly different breast microbiome. Gut barrier dysfunction was associated with increased a-diversity and significant different β-diversity in the breast tissue. Taken together our data supports the presence of a breast microbiome influenced by diet that largely varies from the gut microbiome population but is, however, sensitive to gut permeability. [ABSTRACT FROM AUTHOR]

Children with nonalcoholic fatty liver disease (NAFLD) display an altered gut microbiota compared with healthy children. However, little is known about the fecal bile acid profiles and their association with gut microbiota dysbiosis in pediatric NAFLD. A total of 68 children were enrolled in this study, including 32 NAFLD patients and 36 healthy children. Fecal samples were collected and analyzed by metagenomic sequencing to determine the changes in the gut microbiota of children with NAFLD, and an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system was used to quantify the concentrations of primary and secondary bile acids. The associations between the gut microbiota and concentrations of primary and secondary bile acids in the fecal samples were then analyzed. We found that children with NAFLD exhibited reduced levels of secondary bile acids and alterations in bile acid biotransforming-related bacteria in the feces. Notably, the decrease in Eubacterium and Ruminococcaceae bacteria, which express bile salt hydrolase and 7α-dehydroxylase, was significantly positively correlated with the level of fecal lithocholic acid (LCA). However, the level of fecal LCA was negatively associated with the abundance of the potential pathogen Escherichia coli that was enriched in children with NAFLD. Pediatric NAFLD is characterized by an altered profile of gut microbiota and fecal bile acids. This study demonstrates that the disease-associated gut microbiota is linked with decreased concentrations of secondary bile acids in the feces. The disease-associated gut microbiota likely inhibits the conversion of primary to secondary bile acids.

Children with nonalcoholic fatty liver disease (NAFLD) display an altered gut microbiota compared with healthy children. However, little is known about the fecal bile acid profiles and their association with gut microbiota dysbiosis in pediatric NAFLD. A total of 68 children were enrolled in this study, including 32 NAFLD patients and 36 healthy children. Fecal samples were collected and analyzed by metagenomic sequencing to determine the changes in the gut microbiota of children with NAFLD, and an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system was used to quantify the concentrations of primary and secondary bile acids. The associations between the gut microbiota and concentrations of primary and secondary bile acids in the fecal samples were then analyzed. We found that children with NAFLD exhibited reduced levels of secondary bile acids and alterations in bile acid biotransforming-related bacteria in the feces. Notably, the decrease in Eubacterium and Ruminococcaceae bacteria, which express bile salt hydrolase and 7α-dehydroxylase, was significantly positively correlated with the level of fecal lithocholic acid (LCA). However, the level of fecal LCA was negatively associated with the abundance of the potential pathogen Escherichia coli that was enriched in children with NAFLD. Pediatric NAFLD is characterized by an altered profile of gut microbiota and fecal bile acids. This study demonstrates that the disease-associated gut microbiota is linked with decreased concentrations of secondary bile acids in the feces. The disease-associated gut microbiota likely inhibits the conversion of primary to secondary bile acids. [ABSTRACT FROM AUTHOR]

Metagenomics data provide rich information for the detection of foodborne pathogens from food and environmental samples that are mixed with complex background bacteria strains. While pathogen detection from metagenomic sequencing data has become an activity of increasing interest, shotgun sequencing of uncultured food samples typically produces data that contain reads from many different organisms, making accurate strain typing a challenging task. Particularly, as many pathogens may contain a common set of genes that are highly similar to those from normal bacteria in food samples, traditional strain-level abundance profiling approaches do not perform well at detecting pathogens of very low abundance levels. To overcome this limitation, we propose an abundance correction method based on species-specific genomic regions to achieve high sensitivity and high specificity in target pathogen detection at low abundance. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions.Methods: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period.Discussion: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.Trial Registration: ClinicalTrials.gov Identifier: NCT01538550 . [ABSTRACT FROM AUTHOR]

Abstract Background Metagenomic sequencing of respiratory microbial communities for pathogen identification in pneumonia may help overcome the limitations of culture-based methods. We examined the feasibility and clinical validity of rapid-turnaround metagenomics with Nanopore™ sequencing of clinical respiratory specimens. Methods We conducted a case-control study of mechanically-ventilated patients with pneumonia (nine culture-positive and five culture-negative) and without pneumonia (eight controls). We collected endotracheal aspirates and applied a microbial DNA enrichment method prior to metagenomic sequencing with the Oxford Nanopore MinION device. For reference, we compared Nanopore results against clinical microbiologic cultures and bacterial 16S rRNA gene sequencing. Results Human DNA depletion enabled in depth sequencing of microbial communities. In culture-positive cases, Nanopore revealed communities with high abundance of the bacterial or fungal species isolated by cultures. In four cases with resistant clinical isolates, Nanopore detected antibiotic resistance genes corresponding to the phenotypic resistance in antibiograms. In culture-negative pneumonia, Nanopore revealed probable bacterial pathogens in 1/5 cases and Candida colonization in 3/5 cases. In controls, Nanopore showed high abundance of oral bacteria in 5/8 subjects, and identified colonizing respiratory pathogens in other subjects. Nanopore and 16S sequencing showed excellent concordance for the most abundant bacterial taxa. Conclusions We demonstrated technical feasibility and proof-of-concept clinical validity of Nanopore metagenomics for severe pneumonia diagnosis, with striking concordance with positive microbiologic cultures, and clinically actionable information obtained from sequencing in culture-negative samples. Prospective studies with real-time metagenomics are warranted to examine the impact on antimicrobial decision-making and clinical outcomes.

BackgroundIncreasing evidence has shown that alterations in the intestinal microbiota play an important role in the pathogenesis of psoriasis. The existing relevant studies focus on 16S rRNA gene sequencing, but in-depth research on gene functions and comprehensive identification of microbiota is lacking.ObjectivesTo comprehensively identify characteristic gut microbial compositions, genetic functions and relative metabolites of patients with psoriasis and to reveal the potential pathogenesis of psoriasis.MethodsDNA was extracted from the faecal microbiota of 30 psoriatic patients and 15 healthy subjects, and metagenomics sequencing and bioinformatic analyses were performed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database, cluster of orthologous groups (COG) annotations, and metabolic analyses were used to indicate relative target genes and pathways to reveal the pathogenesis of psoriasis.ResultsCompared with healthy individuals, the gut microbiota of psoriasis patients displayed an alteration in microbial taxa distribution, but no significant difference in microbial diversity. A distinct gut microbial composition in patients with psoriasis was observed, with an increased abundance of the phyla Firmicutes, Actinobacteria and Verrucomicrobia and genera Faecalibacterium, Bacteroides, Bifidobacterium, Megamonas and Roseburia and a decreased abundance of the phyla Bacteroidetes, Euryarchaeota and Proteobacteria and genera Prevotella, Alistipes, and Eubacterium. A total of 134 COGs were predicted with functional analysis, and 15 KEGG pathways, including lipopolysaccharide (LPS) biosynthesis, WNT signaling, apoptosis, bacterial secretion system, and phosphotransferase system, were significantly enriched in psoriasis patients. Five metabolites, hydrogen sulfide (H2S), isovalerate, isobutyrate, hyaluronan and hemicellulose, were significantly dysregulated in the psoriatic cohort. The dysbiosis of gut microbiota, enriched pathways and dysregulated metabolites are relevant to immune and inflammatory response, apoptosis, the vascular endothelial growth factor (VEGF) signaling pathway, gut-brain axis and brain-skin axis that play important roles in the pathogenesis of psoriasis.ConclusionsA clear dysbiosis was displayed in the gut microbiota profile, genetic functions and relative metabolites of psoriasis patients. This study is beneficial for further understanding the inflammatory pathogenesis of psoriasis and could be used to develop microbiome-based predictions and therapeutic approaches.

Background: Increasing evidence has shown that alterations in the intestinal microbiota play an important role in the pathogenesis of psoriasis. The existing relevant studies focus on 16S rRNA gene sequencing, but in-depth research on gene functions and comprehensive identification of microbiota is lacking. Objectives: To comprehensively identify characteristic gut microbial compositions, genetic functions and relative metabolites of patients with psoriasis and to reveal the potential pathogenesis of psoriasis. Methods: DNA was extracted from the faecal microbiota of 30 psoriatic patients and 15 healthy subjects, and metagenomics sequencing and bioinformatic analyses were performed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database, cluster of orthologous groups (COG) annotations, and metabolic analyses were used to indicate relative target genes and pathways to reveal the pathogenesis of psoriasis. Results: Compared with healthy individuals, the gut microbiota of psoriasis patients displayed an alteration in microbial taxa distribution, but no significant difference in microbial diversity. A distinct gut microbial composition in patients with psoriasis was observed, with an increased abundance of the phyla Firmicutes , Actinobacteria and Verrucomicrobia and genera Faecalibacterium, Bacteroides , Bifidobacterium , Megamonas and Roseburia and a decreased abundance of the phyla Bacteroidetes, Euryarchaeota and Proteobacteria and genera Prevotella, Alistipes , and Eubacterium. A total of 134 COGs were predicted with functional analysis, and 15 KEGG pathways, including lipopolysaccharide (LPS) biosynthesis, WNT signaling, apoptosis, bacterial secretion system, and phosphotransferase system, were significantly enriched in psoriasis patients. Five metabolites, hydrogen sulfide (H2S), isovalerate, isobutyrate, hyaluronan and hemicellulose, were significantly dysregulated in the psoriatic cohort. The dysbiosis of gut microbiota, enriched pathways and dysregulated metabolites are relevant to immune and inflammatory response, apoptosis, the vascular endothelial growth factor (VEGF) signaling pathway, gut-brain axis and brain-skin axis that play important roles in the pathogenesis of psoriasis. Conclusions: A clear dysbiosis was displayed in the gut microbiota profile, genetic functions and relative metabolites of psoriasis patients. This study is beneficial for further understanding the inflammatory pathogenesis of psoriasis and could be used to develop microbiome-based predictions and therapeutic approaches. [ABSTRACT FROM AUTHOR]

The pros and cons of monosodium glutamate (MSG), a common food additive, have been long disputed, whereas the effects of MSG consumption on human intestinal microbiome have not been fully understood. In the present study, metagenomics sequencing was performed to evaluate the effects of MSG on human intestinal microbiota (n = 12) during a four-week experiment. It was observed that MSG consumption did not significantly alter the intestinal microbial community structure and functional features of the subjects. Although some bacteria including Faecalibacterium, Megamonas, Blautia and Collinsella tended to change, there was no significant difference in the alteration of all genera. At the functional level, the microbial functions were rich, mainly distributed in membrane transport, amino acid metabolism and carbohydrate metabolism, but there was no significant difference between samples obtained at different times. Additionally, it was discovered that the impact of the individuals on intestinal microbiota was greater than that of MSG.

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Although immunomodulatory activities of Dendrobium officinale polysaccharide has been investigated for many years, yet the potential contribution of its metabolite derived from intestinal microbes on immunoregulation effect has not been reported. In this study, polysaccharide DOW-5B with average molecular weight of 39.4 kDa was isolated from the stem of Dendrobium officinale Kimura et Migo. The carbohydrate content was 91.97% and no protein was detected. The monosaccharide analysis showed this polysaccharide was composed of glucuronic acid and glucose at a molar ratio (M/G) of 1.2:19.4. Animal test indicated DOW-5B increased the diversity of gut microbiota on mice. Beneficial microbes such as Ruminococcus , Eubacterium , Clostridium , Bifidobacterium , Parabacteroides and Akkermansia muciniphila increased while harmful bacteria in Proteobacteria decreased. Surprisingly, DOW-5B promoted gut microbes to generate more butyrate and mainly produced by Parabacteroides HGS0025. Further, we found the health of large intestine as well as immunity response of mice was improved. In addition, Parabacteroides HGS0025 positively correlated with butyrate, IgM, IL-10, and TNF-α products in intestine and mice blood, respectively. The data suggested that Dendrobium officinale polysaccharide has function on immunity may be mediated by butyrate. It adds new evidence to support the basis of how herbal polysaccharides affect immunity. Unlabelled Image [ABSTRACT FROM AUTHOR]

The VIMSS Computational Core group is responsible for data management, data integration, data analysis, and comparative and evolutionary genomic analysis of the data for the VIMSS project. We have expanded and extended our existing tools sets for comparative and functional genomics to deal with new data produced by the VIMSS ESPP2 members. The Computational Core is developing methods to store and analyze diverse data sets including: microarrays, ChIP-chip arrays, tiling arrays, proteomics, metabolomics, metabolic flux, phylochips, metagenomics sequencing, genome sequencing, growth curves, phenotype arrays, knock out strain collections and links to existing literature and web based resources. Our analysis has been incorporated into our comparative and functional genomics website MicrobesOnline (http://www.microbesonline.org) and made available to the wider research community. By taking advantage of data integration across diverse functional and comparative datasets, we have been able to pursue large research projects in evolutionary and systems biology studies. Data management, integration and distribution are critical functions for all large projects. A primary goal of the Computational Core is to capture all experimental data from the ESPP2 investigators, including relevant metadata, raw data and processed data, and to make these data sets available through intuitive queries. Our group has developed Experimental Information and Data Repository (http://vimss.lbl.gov/EIDR/) and the MicrobesOnline database to provide this functionality. Researches have access to datasets from biomass production, growth curves, image data, mass spec data, phenotype microarray data and transcriptomic, proteomic and metabolomic data. New functionality has been added for storage of information relating to mutant strains, transposon knockout libraries and protein complex data, in addition to new visualization for assessing existing data sets such as the phenotype microarrays. The Computational Core has focused on using the data generated by the ESPP2 project to understand the stress response of Desulfovibrio vulgaris Hildenbourgh. We work closely with the other core groups within the ESPP2 project to assist in data analysis. Over the past year, this has included co-culture laboratory evolution, 16S barcode data, and phenotype analysis for the Applied Environmental Microbiology Core (AEMC) and transcriptomic, tiling arrays, and metabolite analysis for the Functional Genomics Core (FGC). New research being pursued this year by the Computational Core includes: development of new methods for data compendium analysis using biclustering which combines transcriptomic, proteomic, interaction and gene neighborhood data in order to predicted regulatory structures; computational predictions of amino acid synthesis pathways in DvH (working closely with the FGC to verify predictions); evolutionary analysis of lineage specific gene expansion across bacteria; sub N squared phylogenetic tree reconstruction by developing the FastTree program; and large scale comparative metagenomic sequence analysis. The MicrobesOnline database (http://www.microbesonline.org) currently holds over 1000 microbial genomes and will be updated semi-annually, providing an important comparative and functional genomics resource to the community. New functionality added this year includes the addition of fungal genomes and the framework for adding additional eukaryotic genomes, an updated user interface for the phylogenetic tree based genome browser that allows users to view their genes and genomes of interest within an evolutionary framework, improved tools to compare multiple microarray expression data across genes and genomes, phylogenetic profile searches using our high quality species tree, and addition of external microarray data from the Many Microbial Microarrays Database for bacteria and Yea

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Molluscum contagiosum is a common, self-limiting infectious disease of the skin caused by molluscum contagiosum virus (MCV). The disease primarily affects children, sexually active adults, and immunocompromised individuals. Transmission of the virus occurs by direct skin contact. Therefore, the virus is usually detected in the skin and genitals of patients. However, the diagnosis of intracranial infection by the virus is difficult if the skin/mucosa lessons are atypical or absent, and the presence of the virus in the cerebrospinal fluid has not been reported. We report a very rare case of intracranial infection by molluscum contagiosum virus. A 25-year-old girl was admitted to our hospital due to severe headache but no fever or other symptoms. Upon examination, some small flesh-colored flattened papules on both arms were noticed. Blood tests showed slightly reduced levels of CD3 and CD4 T lymphocytes. Three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) and head magnetic resonance (MR) were both normal. Lumbar puncture was performed, and metagenomic sequencing was applied to the spinal fluid. The unique sequences of the molluscum contagiosum virus were identified in the fluid. The patient was then diagnosed with intracranial molluscum contagiosum virus infection. No special treatment was given. The headache gradually disappeared, and the patient was discharged. During our quarterly follow-up, the girl appeared normal, and her skin lesions disappeared. However, her CD3 and CD4 T lymphocyte counts were still slightly lower than the normal level. Our case shows that the application of metagenomic sequencing to cerebrospinal fluid is a sensitive and powerful means to detect pathogens causing intracranial infection. [ABSTRACT FROM AUTHOR]

Omics data usually have ultra-high dimension (p) and small sample size (n). Standard support vector machines (SVMs), which minimize the L2 norm for the primal variables, only lead to sparse solutions for the dual variables. L1 based SVMs, directly minimizing the L1 norm, have been used for feature selection with omics data. However, most current methods directly solve the primal formulations of the problem, which are not computationally scalable. The computational complexity increases with the number of features. In addition, L1 norm is known to be asymptotically biased and not consistent for feature selection. In this paper, we develop an efficient method for sparse support vector machines with L0 norm approximation. The proposed method approximates the L0 minimization through solving a series of L2 optimization problems, which can be formulated with dual variables. It finds the optimal solution for p primal variables through estimating n dual variables, which is more efficient as long as the sample size is small. L0 approximation leads to sparsity in both dual and primal variables, and can be used for both feature and sample selections. The proposed method identifies much less number of features and achieves similar performances in simulations. We apply the proposed method to feature selections with metagenomic sequencing and gene expression data. It can identify biologically important genes and taxa efficiently. [ABSTRACT FROM AUTHOR]

Highlights • Metagenomics sequencing performed well in diagnosing PCP compared to conventional methods. • Metagenomics exhibited the ability to detect co-infections in PCP patients. • Blood samples metagenomics might suit patients who couldn't tolerate invasive procedures. • Pathogen reads ranking and proportion rate may be the promising cutoff value. [ABSTRACT FROM AUTHOR]

Composition of the gut microbiota has been linked with human immunedeficiency virus (HIV)-infected patients on antiretroviral therapy (ART). Evidence suggests that ART-treated patients with poor CD4+ T-cell recovery have higher levels of microbial translocation and immune activation. However, the association of the gut microbiota and immune recovery remains unclear. We performed a cross-sectional study on 30 healthy controls (HC) and 61 HIV-infected individuals, including 15 immunological ART responders (IRs), 20 immunological ART non-responders (INRs) and 26 untreated individuals (VU). IR and INR groups were classified by CD4+ T-cell counts of ≥350 cells/mm3 and

Graphical abstract Highlights • No significant changes were observed in community structure of intestinal microbiota before and during the consumption of MSG. • There were no obvious effects on microbial metabolic functional features in the process of monosodium glutamate consumption. • The impact of the individuals on intestinal microbiota was greater than that of MSG. Abstract The pros and cons of monosodium glutamate (MSG), a common food additive, have been long disputed, whereas the effects of MSG consumption on human intestinal microbiome have not been fully understood. In the present study, metagenomics sequencing was performed to evaluate the effects of MSG on human intestinal microbiota (n = 12) during a four-week experiment. It was observed that MSG consumption did not significantly alter the intestinal microbial community structure and functional features of the subjects. Although some bacteria including Faecalibacterium , Megamonas, Blautia and Collinsella tended to change, there was no significant difference in the alteration of all genera. At the functional level, the microbial functions were rich, mainly distributed in membrane transport, amino acid metabolism and carbohydrate metabolism, but there was no significant difference between samples obtained at different times. Additionally, it was discovered that the impact of the individuals on intestinal microbiota was greater than that of MSG. [ABSTRACT FROM AUTHOR]

Composition of the gut microbiota has been linked with human immunedeficiency virus (HIV)-infected patients on antiretroviral therapy (ART). Evidence suggests that ART-treated patients with poor CD4+ T-cell recovery have higher levels of microbial translocation and immune activation. However, the association of the gut microbiota and immune recovery remains unclear. We performed a cross-sectional study on 30 healthy controls (HC) and 61 HIV-infected individuals, including 15 immunological ART responders (IRs), 20 immunological ART non-responders (INRs) and 26 untreated individuals (VU). IR and INR groups were classified by CD4+ T-cell counts of ≥350 cells/mm3 and <350 cells/mm3 after 2 years of ART, respectively. Each subject’s gut microbiota composition was analyzed by metagenomics sequencing. Levels of CD4+ T cells, CD8+HLA-DR+ T cells and CD8+CD38+ T cells were measured by flow cytometry. We identified more Prevotella and fewer Bacteroides in HIV-infected individuals than in HC. Patients in INR group were enriched with Faecalibacterium prausnitzii, unclassified Subdoligranulum sp. and Coprococcus comes when compared with those in IR group. F. prausnitzii and unclassified Subdoligranulum sp. were overrepresented in individuals in VU group with CD4+ T-cell counts <350 cells/mm3. Moreover, we found that the relative abundance of unclassified Subdoligranulum sp. and C. comes were positively correlated with CD8+HLA-DR+ T-cell count and CD8+HLA-DR+/CD8+ percentage. Our study has shown that gut microbiota changes were associated with CD4+ T-cell counts and immune activation in HIV-infected subjects. Interventions to reverse gut dysbiosis and inhibit immune activation could be a new strategy for improving immune reconstitution of HIV-1-infected individuals. [ABSTRACT FROM AUTHOR]

Corydalis saxicola Bunting (CS), a traditional Chinese folk medicine, has been effectively used for treating liver disease in Zhuang nationality in South China. However, the main anti-liver fibrosis ingredients in CS are incompletely understood. To elucidate the main anti-liver fibrosis ingredients in CS and its underlying mechanism. Firstly, spectrum-effect relationship (SER) strategy was applied to identify the major ingredients against liver fibrosis in CS. Subsequently, 1H NMR metabonomics and metagenomics sequencing techniques were used to clarify the intervention of palmatine (PAL) on liver fibrosis. Furthermore, the expression of tight junction proteins and the levels of liver inflammation factors were examined, the effect of PAL on microbiota was verified by FMT. The SER model revealed that PAL was the most important active ingredient in CS. 1H NMR fecal metabonomics showed that PAL could reserve the abnormal levels of gut microbial-mediated metabolites of liver fibrosis, such as isoleucine, taurine, butyrate, propionate, lactate, glucose, which mainly involved in amino acid metabolism, intestinal flora metabolism and energy metabolism. Metagenomics sequencing found that PAL could callback the abundance of s__Lactobacillus_murinus, s__Lactobacillus_reuteri, s__Lactobacillus_johnsonii, s__Lactobacillus_acidophilus and s__Faecalibaculum_rodentium to varying degree. Furthermore, the intestinal barrier function and the levels of hepatic inflammation factors were significantly ameliorated by PAL. FMT demonstrated that the therapeutic efficiency of PAL was closely associated with gut microbiota. The effects of CS on liver fibrosis were attributed in part to PAL by alleviating metabolic disorders and rebalancing gut microbiota. The SER strategy may be a useful method for the discovery of active constituents in natural plants. • SER strategy was used to identify the main active ingredients in CS. • PAL was revealed as the main component of CS against liver fibrosis. • PAL could improve CCl 4 -induced liver fibrosis by ameliorating metabolic disorder and rebalancing gut microbiota. [ABSTRACT FROM AUTHOR]

[Display omitted] • Environmental persistent free radicals enhanced hydrolases activity. • Environmental persistent free radicals improved the ratio of coenzyme factor pair. • The abundance of the propionic acid-related ([EC:7.1.1.2]) gene was increased. • The methanogenesis ([EC:2.1.1.86]) was inhibited. The conversion of organic matter in waste activated sludge (WAS) into high value-added chemicals of volatile fatty acids (VFAs) has become a focus of attention worldwide. However, the conversion of WAS to a certain acid among VFAs is difficult. Herein, for the first time, biochar was used to promote sludge solubilization, hydrolysis and acidogenic fermentation for the production of propionic acid. The results illustrated that biochar (prepared at 450 °C, containing environmental persistent free radicals (EPFRs) of 15.91 × 1015 spins/g) stimulated sludge solubilization, hydrolysis and VFAs production, enhancing sludge cell lysis rate, VFAs production, propionic acid ratio, protease, α-glucosidase and nicotinamide adenine dinucleotide hydrogen (NADH)/nicotinamide adenine dinucleotide (NAD+) ratio by 10.53 %, 107.42 %, 17.52 %, 68 %, 32 % and 76.10 % respectively, compared with those observed in the control group without biochar addition. And once the EPFRs were shielded, they decreased. The signal of EPFRs decreased from 15.91 × 1015 spins/g to 15.20 × 1015 spins/g on day 2 and 8.50 × 1015 spins/g on day 4. The EPFRs contained in the biochar played an important role in the intermediary function and interfered with the bacterial metabolic pathways. Metagenomics sequencing also revealed that biochar EPFRs promoted the sludge acidogenic fermentation to produce propionic acid ([EC:7.1.1.2]) and partly inhibited acetic acid production ([EC:1.2.1.3]). This study reveals that biochar could promote sludge solubilization, hydrolysis and promote propionic acid production, which could be used as a new strategy for acid production in the future. [ABSTRACT FROM AUTHOR]

• Diosgenin reduces bone loss in ovariectomized rats. • Diosgenin restores the composition of GM in ovariectomized rats. • Diosgenin prevents the up-regulation of metabolism pathways. Diosgenin (DIO) is an aglycone of steroid saponins acquired from plants, including Dioscorea alata , Smilax China , and Trigonella foenum graecum , acting as an anti-osteoporosis, anti-diabetic, anti-hyperlipidemic, anti-inflammatory. Recent studies have demonstrated that DIO reduces bone loss. This study aimed to investigate the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats. Female Sprague-Dawley rats were randomly divided into sham operation (sham + vehicle group) or ovariectomy. For 12 weeks, OVX rats were treated using a vehicle (OVX + vehicle group) and DIO (OVX + DIO group). Subsequently, ELISA was conducted to determine serum estradiol levels, micro-CT scanning was performed to evaluate bone quality, and feces were collected for metagenomics sequencing to examine the structure and function of GM. Raw reads were filtered to remove chimera sequences. Operational taxonomic units (OTUs) were clustered in the filtered reads. A Venn diagram analysis was conducted to study the common and unique OTUs in the sham + vehicle, OVX + vehicle, and OVX + DIO groups. LEfSe analysis was conducted to evaluate the specific GM of the three groups. The GM functions were analyzed using the KEGG and CAZy databases. After a 12-week treatment, DIO administration prevented OVX-induced weight gain and increased the estradiol levels. DIO treatment improved the bone microstructure and structural parameters of rat tibias. Metagenomics sequencing results identified 1139, 1207, and 1235 operational taxonomic units (OTUs) in the sham + vehicle, OVX + vehicle, and OVX + DIO groups, respectively. The percentage of common OTUs was 41.2%. Treatment with DIO restored the composition of GM in OVX rats by increasing the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia_idealis and reducing the abundance of Betaproteobacteria, Gammaproteobacteria, Methanobacteria, Bacteroides, Phocaeicola, Alistipes, Bacteroids_uniformis, Bacteroids_xylanisolvens. The anti-osteoporosis effect of DIO can be regulated through environmental information processing, organismal Systems, Cellular Processes, human diseases, metabolism, and genetic information processing. Meanwhile, treatment with DIO improved GM homeostasis by increasing the metabolism of carbohydrates, other amino acids, and glycans and reducing translation, energy metabolism, and nucleotide metabolism. DIO can reduce bone loss by regulating the structural composition and function of GM, a novel strategy for preventing osteoporosis. [ABSTRACT FROM AUTHOR]